Genes, learning, behaviour and the outside world

This essay was written by Jamshed Tata and was first published in the 2003 Mill Hill Essays.

In 1874 Francis Galton, half-cousin of Charles Darwin and grandson of Erasmus Darwin, introduced the concept of Nature versus Nurture, which followed the publication of his book Hereditary Genius in 1869. He pointed out that his own high level of intelligence was inherited from a shared ancestry with the Darwins and other relatives and was soon to take up an increasingly extreme and dogmatic position by emphasizing that we were not created equal. This view later gave birth to the pseudo-science of eugenics. An opposite, but equally dogmatic, stance was taken by J. B. Watson and his followers for whom we are what we are because we have been shaped from birth by external influences and learning and not because of inherited innate differences. As a result, an ongoing debate has raged over the last several decades, spawning divergent views on the importance of nature (read genes) as opposed to nurture (read environment) to explain human development, diseases and behaviour. This debate has drawn in a large number of distinguished geneticists, behaviourists, educationists and social scientists. In his latest book Nature via Nurture: Genes, Experience and What Makes Us Human (Fourth Estate, 2003), Matt Ridley concludes that the debate is futile and proposes that our genes can influence how we respond to external influences, while environmental factors can determine how our genes function.

Ridley has divided his book into ten highly readable chapters, each subdivided into relatively brief topics. He states at the very outset in the prologue that his book is going to change most radically our thinking on such matters as genes and behaviour or nature vs. nurture. He writes:

The discovery of how genes actually influence human behaviour, and how human behaviour influences genes, is about to recast the debate entirely. No longer is it nature-versus-nurture, but nature-via-nurture. Genes are designed to take their cues from nurture. To appreciate what has happened, you will have to abandon cherished notions and open your mind. You will have to enter a world where your genes are not puppet masters pulling the strings of your behaviour, but are puppets at the mercy of your behaviour; a world where instinct is not the opposite of learning, where environmental influences are sometimes less reversible than genetic ones, and where nature is designed for nurture.

This statement encapsulates the essential argument that Ridley is set to develop in his book, namely to provide new insights and re-evaluate some fundamentals of biology, psychology and social sciences. Has he achieved these goals or are these merely hollow claims and new packaging of old ideas? How valid is the scientific foundation on which he builds this edifice?

Consider the first chapter of Nature via Nurture, entitled “The paragon of animals”, which assembles a large number of diverse and interesting facts, some well-known, others somewhat obscure, to view evolution in terms of modern genetics. A sub-heading with the title “The Simian Soap Opera” starts with Jane Goodall’s anthropomorphic description of chimpanzees, about how they are similar to us and how her observations have eliminated the idea of human ‘exceptionalism’. He also considers the counter-argument which doubts whether chimps (and other apes) can be said to have a mind in the human sense, and then concludes that both similarity and differences co-exist. Of course, Darwin had already proposed that the differences are a matter of degree and not of kind. The anatomical similarities (e.g. five digits, body hair) can now be easily explained by the 98+% identity of genes between apes and humans. But there are real differences when one contrasts anatomy with social behaviour, which Ridley illustrates with the sex lives of African apes and Asian orang-utans.

These studies of field primatology focusing on social and sexual behaviour lead Ridley to conclude that we humans are a unique species. He also reminds the reader of how the similarities between species have been maintained through evolution, much of the information coming from the recent rapid advances of biological technologies. He is struck by the figure of 98.6% similarity between chimpanzee and human genomes. In the prologue he had already emphasised the importance of understanding genes and that the 30,000 genes of man, fewer than thought at one time, can account for billions of permutations underlying every aspect of our physiology, diseases, behaviour and personality.

The dilemma of ‘similar but yet different’ is resolved not by similarities and differences between the genes of different species, but in the diverse ways in which they are expressed, described as ‘throwing switches’. Genetic similarities are not only shared between man and apes but, more importantly, also with mice, frogs, flies, worms, and even plants. So how are the differences generated? The answer lies in differential gene expression, which actually has been intensively studied for the last forty or fifty years. One gets the feeling that Matt Ridley has recognised the importance of this phenomenon of regulatory biology only recently. He is quite rightly impressed by genes underlying the control of body plan and morphogenesis during development. What he finds particularly striking is that during evolution “the same gene can be reused in different places and at different times“. For him, differential gene expression does not only resolve the dilemma of ‘similar but different’ but allows the extrapolation that “nurture can start to express itself through nature“.

Francis Galton had introduced the ‘convenient jingle’ of nature and nurture. He was stung by the criticism that while talent and intelligence runs in families, achievement owed more to circumstance and opportunity than to innate genius. It prompted him, in his new book published in 1874 “English Men of Science: Their Nature and Nurture”, to emphasise that scientific geniuses are born, not made. Galton decided to test his ideas by studying identical and non-identical twins. Finding that the former remained similar throughout life, not only in their appearance but also in their health, personality, etc., while the latter became increasingly dissimilar even though the twins were exposed to the same external influences, he concluded that “nature prevails enormously over nurture“. Whether or not one agrees with Galton’s excessive dogmatism, his understanding of heredity is remarkable, especially considering that the term ‘gene’ was only coined at the beginning of the twentieth century. To this day studies of human twins constitutes an important tool for genetic studies of physiology, diseases, behaviour and virtually every function. But one must also not forget that Galton’s ideas on the elimination by the state of undesirable features in populations contributed (albeit indirectly) a few decades later to the abuse of eugenics by the Nazis in Germany.

Studies on twins reinforced the emergence of behaviour genetics. They have also enhanced the idea of heritability of personality, simply because identical twins raised apart are more similar than fraternal twins also raised apart. Thus personality is some intrinsic part of their nature, which means that innate character is unlikely to be much influenced by the family they grew up in or by some other environmental factors (nurture). Ridley attempts to answer the question as to what gene can be responsible for personality variations by citing some recent findings on the association between mutations in a particular gene in some people with certain forms of neurosis, depression, anxiety and some facets of personality. Not only is the evidence for this type of association highly circumstantial, personality and its diverse aberrations are most certainly the product of a complex interplay of multiple genes. Although he is optimistic that the association between a gene and depression promises a treatment of this illness, it remains at best a distant hope.

The second chapter (“a plethora of instincts”) moves from genes to psychology, starting with William James’ contention that humans have more instincts than animals, such as sociability, shyness, secretiveness, cleanliness, modesty, shame, jealousy. For Ridley, however, the most important of them all is sexual attraction, or more poetically, ‘love’. Digressing here, he explains the latter instinct being under the control of hormones, which, in turn, control the activities of certain genes active in different parts of the brain and which specify the various instincts. For example, Insel’s experiments of injecting the hormones oxytocin and vasopressin into the brain showed that these provoked different behavioural and sexual responses in male and female animals. Since oxytocin receptor genes in different animal species have promoters of different lengths, Ridley speculates that this result may explain the variety of mating and bonding preferences in different species.

No discussion of instincts is complete without considering the work of the Dutch ethologist Niko Tinbergen on birds and fish showing that innate instincts can be triggered by external stimuli. That animal behaviour is controlled by specific genes was beautifully demonstrated by Seymour Benzer with his mutational analysis of fruit-fly behavioural patterns. Turning to human behaviour, Ridley discusses in some detail the work of the psychologists John Money and Mickey Diamond in the United States. According to Money humans at birth are psychosexually neutral and that gender orientation as male or female is not innate but is acquired later through learning and experience. Diamond opposed this view that sexual behaviour was environmentally determined and few now subscribe to Money’s views. The Y chromosome, and hence the expression of certain genes, is undoubtedly important in determining behavioural patterns. What is innate and what is not can be partly explained by looking at differences in the normal and abnormal behaviour of boys and girls during their development. However, in some egg-laying species sex determination is known to be controlled by environmental factors such as temperature of incubation of eggs, while hormonal imbalances during gestation in mammals can exert irreversible influences on behavioural patterns during adult life. In other words, both genes and environment play important, and often complex and interdependent, roles in determining behaviour. Ridley concludes this part of discussion of nature vs. nurture by saying “I propose to end each chapter mocking the utopia implied in taking any theory too far“.

Violent reaction was provoked among scientists, writers, media, etc. by the appearance in the late sixties of the views of Arthur Jensen that intelligence is inherited and the publication of The Bell Curve by Richard Herrnstein and Charles Murray. In the 1920s, particularly in the United States and in some European countries, many subscribed to the view that stupid or unintelligent people tended to breed excessively, which led some countries to carry out forced sterilisation of mental defectives to limit the spread of deleterious genes among their populations. A search for a gene controlling ‘general intelligence’ has proved fruitless and it is hard to see how this can be accomplished. An interesting point made by Ridley is that the intellectual experience of a child is generated by others, whereas an adult generates his or her own intellectual potential. He concludes that Galton was wrong about nature prevailing over nurture, but argues that nature and nurture are not “rivals” and not competing.

From a discussion of intelligence Ridley moves on to mental illness, begining with Kraeplin’s pioneering work in psychiatry in Germany in the late 19th century when he introduced the procedure of recording personal histories of his patients, a practice that preceded Freud’s introduction of psychoanalysis. When speculating on the causes of schizophrenia Ridley points out the shortcomings of laying too much emphasis on childhood experiences and ignoring biological explanations (he finds that the ready acceptance of psychoanalysis in the mid-twentieth century owes more to marketing than therapeutic success). By quoting observations on identical twins, in whom the appearance of schizophrenia shows the extraordinarily high 70-80% concordance, he concludes that this mental illness is more a question of nature than nurture and that psychosocial factors are of little consequence, if at all. What genes can be responsible for schizophrenia? Initially the Icelandic studies showing that a piece of chromosome 5 was abnormal caused much excitement and many predicted that a schizophrenia gene would soon be identified. But the failure to reproduce these findings by other investigators has led to the current consensus that we are dealing here with a multigenic cause of the disease. Defective neurotransmitters and their receptors (e.g. dopamine and glutamate receptors) have also been suggested as likely causes of schizophrenia and other disorders of the mind. Indeed, schizophrenia has now been linked to just about every human chromosome, and, if one accepts the most likely situation that different mutations occur on different genes, then the search for a unique schizophrenia gene will surely be a futile one. With the exception of a few disorders , such as Huntington’s and phenylketonuria (PKU), most mental diseases are likely to be similarly multigenic. A major problem and source of confusion here is the frequent inability to distinguish cause and effect. The failure to link specific genes with heritable mental diseases has meant that environmental factors or earlier experiences should not be ignored. These include viral infections, stress, diet and so on, thus emphasizing the role of nurture, so that predisposing genes are necessary but not sufficient for a given disorder to develop. For Ridley, genes are the means by which nurture expresses itself, and concludes that “the ultimate explanation for schizophrenia will include both nature and nurture, neither of which will be able to claim primacy“.

A chapter entitled Genes in the Fourth Dimension begins with the views of the Swiss child psychologist Jean Piaget who took the middle road between Lorenz championing nature and B.F. Skinner nurture. Ridley gives credit to Piaget for his support of the time dimension (in other words, development) and labels it the fourth dimension of human nature. It is the debate between Lorenz, with his belief that instincts are genetically inherited, and Lehman, supporting the concept that external experiences can cause internal biological changes, which he finds particularly rewarding. Lorenz had completely ignored development in the establishment of behavioural patterns. Those of us who are interested in developmental mechanisms could not agree more about its importance, but I could not help feeling that Ridley has oversimplified development. He is quite receptive to the analogy drawn by the British biologist Patrick Bateson between behavioural and psychological development and cooking, where the raw ingredients (genetic and environmental factors) can be the same but it is the manner in which they are combined (development) that is important. This analogy has been interpreted in opposite ways for the nature vs. nurture argument, as, for example, by Richard Dawkins for whom it is all in our genes and Steven Rose responding that behaviour is not determined by our genes. There is a big chasm between developmental mechanisms and behaviour. Even though the development of an organism seems complicated enough, it is now emerging that some of the processes of early embryogenesis, patterning and morphogenesis, can be traced back to the activities of specific genes, often acting in concert. But no such connection has yet been made for the development of behaviour by specific genes.

More relevant to the discussion of nature and nurture are the simple behavioural experiments performed on the nematode worm Caenorhabditis elegans in which new neurons can be formed by schooling and learning. These exert their effects at the same synapses by altering the expression of the same genes, which suggests that development of behaviour can be environmentally plastic. Going further up the evolutionary scale are the behavioural effects of maternal influences mediated via hormonal signals acting on newborn mice. Ridley concludes that this type of evidence “reinforces my message that genes are servants of nurture as much as they are servants of nature”.

Lorenz had introduced the concept of critical periods during development, with well-defined time-windows, which led to the recognition of imprinting. According to Ridley, this view of environment shaping behaviour in his ducklings and goslings via imprinting can be explained in another way, namely through influences during gestation, i.e. an environmental trigger coming into play before birth or, as in the case of his birds, hatching. Such pre-natal influences naturally diminish the importance of instinct and, in some ways, also that of post-natal environmental factors. There is in fact much evidence in mammals that hormonal imbalance or severe nutritional deprivation during gestation can lead to permanent alterations in behaviour during the post-natal period lasting through adult life. The perturbations, or even reversal, of sexual and other behaviour in adult, male and female dogs and monkeys, following the administration of testosterone and oestrogen to the foetuses is often cited in support of these ideas. Work in the 1960s by some vision physiologists, such as David Hubel, has led to much experimentation establishing the plasticity of the developing brain, which certainly forms the basis of imprinting. More recently, a gene expressed in the brain has been thought to facilitate imprinting through visual stimuli during development by virtue of its ability to control the maturation of the gamma amino butyric acid (GABA) system. Of course, observations of this kind merely reflect one of the consequences, but say nothing about the causes, of imprinting.

In humans, except for twins, the pre-natal experience is not shared by the siblings, so that the gestational (maternal) influences are unique to every individual. For Ridley, not only is nurture reversible and nature not, but nurture can play its role both before and after birth. Such conclusions often lead to much argument when explaining homosexuality or discussing Freudian analysis of behaviour. A more biological approach to sexual identity is that of trying to understand sex determination. Thanks to some pioneering work done at the NIMR by Robin Lovell-Badge and his colleagues, the foetal expression of the SRY gene, located on the Y chromosome, sets off a chain reaction of downstream genes coming into play, which eventually set up male anatomical and behavioural characteristics. In mammals, but not in egg-laying animals, female is the ‘default’ sex. If the SRY gene is incorrectly expressed or not expressed, or if the gene is missing, the foetus develops into a female. Some have extrapolated that homosexuality may result from this gene failing to cause pre-natal masculinisation in the brain during gestation. Others have considered mutations or mis-expression of other genes leading to an auto-immune reaction by the mother and which would mark the baby for life. These and other examples can be found in chapter 6 entitled Formative Years.

At the beginning of the twentieth century Ivan Pavlov’s conditioned reflex experiments on dogs caused great excitement in both the scientific and lay worlds. In stark contrast to Galton’s views, Pavlov was convinced that 99.9% of the “contents of the mind” are due to education and the rest to ‘individuality’. Later, this idea was extended to the concept that stimulus and reward presented together lead to active learning, so that by the mid-1920s many human psychologists grew increasingly enthusiastic about nurture dominating nature. But how do genes come into this equation? For this we have to turn to the fruit fly. A series of classical experiments carried out in the 1970s by Seymour Benzer’s laboratory at Caltech, involving electric shocks given to the fly’s foot at the same time as whiffs of vapours with different smells, demonstrated that the fly can learn and remember association between smells and electric shocks. Mutational analysis revealed that this association was dependent on certain genes, seventeen of which were identified. These genes have to be activated, i.e. the corresponding proteins expressed, during the learning process. It is easy to imagine how complex a problem it will be to find genes responsible for learning. Coming to humans and learning, Ridley assesses the views of the guru of behaviourism, Burrhus Skinner, who proposed that people do not have instincts, but merely process signals from the environment to an appropriate response, and that innate knowledge had nothing to do with it. He charts the rise and fall of Skinnerism by pitting him against work by others on baby monkeys who had learned to accept pieces of rags as their mother and that monkeys acquired phobias through a process of learning, which itself is an instinct. For Ridley, these results serve once more to prove the main point in his book that genes are not only involved in nature but that they are just as intimately involved in nurture also.

Pavlov’s very success took an unexpected and sinister turn following the revolution in Russia, from which education and research in life sciences in the Soviet Union did not recover for two generations. Lenin was convinced that man, along with other forms of life, can be changed to an “improved version”. This was the perfect opportunity for Ivan Mitchurin, a cranky apple breeder, who had claimed that watering pear trees with sugared water caused the fruits from the next generation of pear trees to be sweeter. Unbelievable as it may sound now (all this happened less than a hundred years ago!), Mitchurin was made a state hero and Mitchurinism soon replaced Mendelism. It created a perfect oppurtunty for his student Trofim Lysenko to promote his idea that wheat could be trained to survive frost (a process called ‘vernalisation’), such that spring wheat thus trained could replace hardy winter wheat. Millions of hectares of wheat were consequemtly lost, to be followed by famine and devastation on a most immense scale. But Lysenko continued to grow in stature and political power. Subjects like DNA, genes and Darwinism were banned (until 1961) from the education and science systems of the Soviet Union, while many reputable geneticists and biologists who refused to toe the line lost their lives or finished their days in the gulag. All this happened during the same period when scientists and politicians in Nazi Germany espoused the opposing cause of eugenics to promote a superior race and eliminate undesirable populations. Man has indeed paid a heavy price for dogmatically promoting both nature and nurture!

What makes us humans so different from chimps and gorillas, if our DNAs are so similar? Many consider that it is the acquisition by a developing child of language, the ability to manipulate tools, transmit information and accumulate culture – functions that are modified and passed on from generation to generation. This is also one of the main themes of a recent book Quest by Charles Pasternak. For Ridley the acquisition of culture is an important issue. He sees no difference between high-brow culture (e.g. listening to La Traviata) and people “dancing round a camp fire with a bone stuck through your nose”, and emphasizes that modern anthropology is the study of culture and not race. The origin of ethnic differences thus lay with history, experience and circumstance, not with physiology and psychology. He also quotes one of the early founders of sociology who said that human nature is the consequence and not the cause of social forces. Thus there is a universal human nature, while technology and tradition merely refract this nature into local culture. Why Ridley embarks on a lengthy discussion of culture in the context of nature and nurture becomes apparent when he says “I believe that the human capacity for culture comes not from some genes that co-evolved with human culture, but from a fortuitous set of preadaptations that suddenly endowed the human mind with an almost limitless capacity to accumulate and transmit ideas. Those preadaptations are underpinned by genes.” For an experimental scientist this statement would be almost impossible to prove or disprove.

Returning to the importance of language to the progression of human culture, Ridley is impressed by recent work on a mutation in a gene which is thought to be necessary for the development of normal grammar and speech in humans and fine motor control of the larynx. Monkeys and mice also have this gene but have not evolved a vocal language, which he explains by speculating that at some time after 200,000 years ago, a mutant form of this gene appeared in the human race, with key changes, and that the mutant form was so successful that his or her descendants now dominate the species. The ability to manipulate tools and the emergence of technology was the other major contributor to our present-day culture, so that the coming together of language and technology must have dramatically altered the fate of the human species. For Ridley, “We owe our abundance to our collective, not our individual brilliance”. To conclude this discussion of culture some other similar statements are added; for example “Culture seems to be the cart not the horse; the consequence not the cause, of some change in the human brain”, or “Genes do more than carry information; they respond to experience. It is time to reassess the very meaning of the word ‘gene’.” All this makes lively reading, but, again, how does one prove or disprove these pronouncements?

A relatively brief penultimate chapter, titled The seven meanings of ‘gene’, starts with five overlapping definitions of what a gene is: a Mendelian hereditary unit, an interchangeable part common to most organisms, disease-linked unit, functional DNA and, lastly, a switch. I find it hard to comprehend the relevance of this and other definitions. Ridley emphasises that the same gene can be used to produce completely different effects, depending on which other genes are also active. The take-home message here is that genes are a set of developmental switches. To give an example, he returns to the male-determining SRY gene whose function is to switch on another gene which does all the work by turning on a whole slew of genes in different tissues involved with a variety of functions, such as signalling mechanisms, neural development, hormonal cascades and so on. Thus the SRY gene fits all five definitions of an archive, recipe, switch, interchangeable part or ‘health-giver’. One can also view a gene as a unit of selection in the sense of Dawkins’ Selfish Gene. This chapter ends with the stir caused by the publication of Edward O. Wilson’s book Sociobiology, in which he concluded that human behaviour could be the product of ‘scheming’ genes and thus explain such complex issues as homosexuality, ethics and social sciences. No wonder that Wilson was heavily criticized by geneticists, molecular biologists and behaviourologists, which further fuelled the nature-nurture debate. Finally, Ridley concludes with “the author’s message of the book”, namely that genes are merely repositories of information and it is the environment of genes (within and outside the cell) that determines the consequences of their activity. In other words regulation of gene expression by environmental factors is most important for understanding nature-nurture interactions.

A budget of paradoxical morals is how the book ends with seven ‘morals’, the first one of which simply says: Don’t be afraid of genes. They are not gods, they are cogs. The second offers us a key paradigm of psychology which states that personality is acquired from the environment and not from parents. For this Ridley quotes one of the writings of the American psychologist Judith Rich Harris’ contention: Do parents have any long-term effects on the development of their child’s personality? This article examines the evidence and concludes that the answer is no. Many studies of parents and their biological or adopted children have clearly demonstrated that genetic factors predispose the way people react to social environment. Harris believes that environment and genome both have a preponderant influence on the personality of a child, but mainly through the child’s peer group. Ridley adds that at all ages conformity is a feature of human society, and this is one more proof that nature is expressed via nurture. Galton would have disagreed with the fourth moral which has to do with meritocracy. Ridley ends its discussion with the witticism: Egalitarians should emphasise nature; snobs should emphasise nurture. Moral no. 5 about race is dealt with briefly by exploding the basis of scientific racism by emphasizing that genetic difference between individuals is swamped by those between races. Race is merely a proxy for something else. The last two morals deal with individuality and free will. To illustrate individuality he mentions a biochemical study in New Zealand on the X chromosome-linked monoamine oxidase A (MAOA) gene in a cohort of over a thousand children. Men with low MAOA activity who had been maltreated as children committed four times as many violent crimes as those with normal enzyme activity and had also been maltreated as children. It is not enough to have maltreatment but one also has to have a low activity gene. What better experimental confirmation of the validity of this observation than to find that MAOA knock-out mice are more aggressive. In other words, ‘bad’ genotype and environment potentiate each other. The association between free will and a biochemical activity is more tenuous. Ridley mentions the CREB genes that he says ‘run learning and memory’ and whose promoters are ‘designed to be switched on and off by events’. Furthermore, he says, these genes are not just the cause of behaviour but are also its consequence. It is disappointing that the book ends with a rather contrived scientific evidence (in contrast to a remarkable accuracy elsewhere in the book). He draws the final moral: Free will is entirely compatible with a brain exquisitely prespecified by, and run by, genes. The question here is to know how to define free will that would be generally acceptable.

I found Nature via Nurture eminently readable, in no small measure because of its engaging and lucid style. Ridley is a master of communicating complex issues of science, psychology, behaviour and society to the reasonably well informed lay as well as professional reader. Considering that he goes backward and forward from one chapter to the next with issues relating to nature and nurture, I found little repetitiousness. Often, and partly to render the style less turgid, accounts of factual matters, as opposed to opinions, tend to be anecdotal. But there is a comprehensive bibliography for each chapter at the end of the book, as well as a most useful index and glossary. The book will please gene scientists, human geneticists, molecular biologists, many neuroscientists and the medical community. Most of them would have already accepted, before this book appeared, the tenet that the activities of our genes is influenced by environmental factors. That nature and nurture interact is acceptable, but there is much doubt about a ‘two-way traffic’, in particular, how the activities of genes could modify environment. The book is less likely to please some behavioural scientists, psychologists and social scientists. Taken as a whole, I particularly liked the first eight of the ten chapters, but I could not help feeling that at the end Ridley had run out of steam and was looking for some new ideas.

It is always easy to say what an author has left out. If I had to indulge in such activity, I would point out two important and rapidly advancing areas of modern biomedical science particularly relevant to the main theme of a book on nature and nurture. First, there is very little mention of endocrinology, which in the last two decades has established how environmental stimuli, mediated by hormonal (as also growth factors, nutrients, etc.) signals and their receptors, impinge on and modify the expression of specific genes. Second, any description of the higher order of organisation of genetic material has been left out. Our genes do not function as naked DNA but are organized in well-ordered structures into chromatin or chromosomes which determine genetic activity. The emergence of epigenetics has already offered us new insights into a growing number of genetic disorders resulting from faulty X chromosome inactivation. Perhaps Matt Ridley is aware of these gaps and it is hoped that he has decided to include these subjects in his next book. If so, I for one will eagerly await its appearance.

 

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