The remarkable machines that allow us to talk to a friend 3,000 miles away while walking to a restaurant, receive an instantaneous answer to almost any question, stare at a picture of our brain, and be cured of a tumor with the help of radioactive material are the dividends of an intellectual gamble whose successes could not have been anticipated. That gamble was the intuition that the surface phenomena we see, hear, and touch were constructed from arrangements of a relatively small number of invisible things initially called atoms. Physicists learned later that atoms were built from an even smaller number of basic entities which were given the fanciful names quarks, leptons, and bosons.

The advantages of this understanding of the varied properties of things that are not alive persuaded scientists who study living things to adopt the same premise. After the notion of genes as the fundamental causes of an animal’s anatomy and physiology took hold at the end of the nineteenth-century, by the 1980s biologists were convinced that research would reveal direct links between the possession of certain genes and the development of equally particular physical and mental illnesses.

An important reason for the enthusiasm surrounding the search for the genes that account for the variation in psychological properties is the premise that material things are the foundation of everything in nature, including mental phenomena. This belief was strengthened by the fact that the observations revealed by the elegant technologies of accelerators, microscopes, telescopes, and X-ray crystallography supported a materialistic foundation for everything.

A recent sentiment to avoid blaming victims of distress for their unhappiness is a second, less significant, reason for the attraction to genes as the primary movers in all life forms. The increased sympathy for youth and adults raised in poverty or subject to prejudice has restrained the urge to place some of the responsibility for the adaptation failures of these individuals on their families or themselves. Genes provide an attractive alternative explanation for no one can be blamed for inheriting the genes that lead to academic failure, drug addiction, or criminal acts. One problem with this assumption is that the family’s social class is a far better predictor of these adaptation failures in every cultural setting than any known gene.

Extensive research on genes over the past 20 years has complicated an earlier, simpler understanding. There is even controversy over the best definition because a gene can’t be defined as a particular string of DNA molecules. It is necessary to add that the DNA string has to be inherited, accompanied by either the DNA or proteins that regulate the inherited string, and the string has to code for one or more proteins that affect the organism’s integrity. Of greater importance is the recognition that every inherited trait, physical or psychological, requires the combination of certain genes along with the contexts in which the person develops. Children who inherit the genes that contribute to verbal skills require a family and school environment that will take advantage of that potential talent. If not, these children will not be able to take advantage of this potential ability. An unknown number of children with special musical or artistic talents will never know they possessed this gift.

The significant contribution of the context also applies to genes. All the cells in each individual contain the same set of genes, but a particular gene can produce different proteins if it is located in heart, lung, or brain because each organ is characterized by its own special physiology. The varied forms that water molecules can assume provides an analogy for water can be a cloud, fog, a gray sky, rain, snow, or an icicle depending on the physical features of the setting. These are some reasons why biologists have been frustrated by their inability to find firm links between genes and psychological traits or mental illnesses.

The phenomenon called depression provides an example. Feelings of apathy and fatigue combined with insomnia, loss of appetite, and a failure to extract pleasure from experiences that had been sources of joy are the defining features of what psychiatrists call a depressive disorder. Although it seems reasonable to assume that this pattern of symptoms is the product of one collection of genes, no one has been able to discover that collection despite many attempts.

An important reason for this failure is that these symptoms, as well as almost all moods, actions, and thoughts, can be generated by more than one causal pathway. Genes influence brain states, but each brain state, in turn, is linked to a limited number of perceptions, feelings, urges to action, or thoughts, with a large gap between any of these psychological products and the more complex phenomena of depression, extraversion, or neuroticism.

Different genes can contribute to exactly the same depressive symptoms. Some depressives inherited risk genes from a parent; in others a novel mutation in a different gene occurred when they were embryos or fetuses. In general, the more common the illness or trait, the less likely it has only one genetic origin. Because the symptoms of a mental or physical disease can be the product of different genes, only some patients improve after taking a medicine designed to remove the symptom. Hence, the move for a personalized therapy in which the therapy is specific to the individual’s genome rather than their symptoms.

An equivalent degree of heterogeneity applies to talents, behaviors, and personality traits. Many psychologists believe that there are five fundamental personality dimensions, called extraversion, neuroticism, agreeableness, conscientiousness, and openness to new ideas, usually measured by replies to a questionnaire. Because each dimension can be the result of different pathways scientists did not find a single significant relation between possession of any of 360,000 genes and variation in any of the dimensions.

A somewhat surprising, discovery was the increase in the number of rare genes, which is associated with the increase in the world’s population over the past 1000 years. The average infant is born with about three dozen novel DNA sequences no one else possesses. Any two persons selected at random differ in about 10 million bases ( a base is one of the four molecules that comprise a DNA string). These brute facts mean that if a rare gene contributed to a mental illness scientists would have to evaluate more than 700,000 individuals in order to detect it.

Moreover, the major human populations in Africa, Asia, Mideast, northern and southern Europe and North and South America vary in many genes. One such variation involves the sensitivity of the receptors on the tongue to sweetness. European Caucasians inherit the genes that render these receptors super sensitive. The variation among populations implies that a particular collection of genes that was a risk for depression in European Caucasians might not place Asians or Africans at risk for these symptoms.

These stubborn facts mean that scientists should parse the currently heterogeneous illness, personality, and skill categories into a number of purer types by gathering additional behavioral and biological evidence. Put plainly, scientists are trying to predict the wrong events from genes. They should instead be trying to find links between genes and less heterogeneous properties that are under firmer genetic control and associated with the more complex trait.

Consider the following example. Some adolescents and adults possess a trio of traits marked by impulsive decisions, low levels of uncertainty when challenges occur, and an easy sociability. A small proportion of this group combine four biological features that are under genetic control. Two features, the ratio of the length of the index finger over the ring finger and the prominence of the chin, are products of the genes controlling secretion of the sex hormones or their receptors. Males have a shorter index than ring finger and, therefore, a smaller ratio, as well as a more prominent chin compared with females. More of these males also possess a muscular body build and a low but variable heart rate. Males with these four features are more likely to display the trio of psychological traits. After finding the genes that contribute to each of these four features, scientists can try to find out whether any of these genes bias males to be impulsive, minimally anxious, or sociable. If successful, they are on their way to parsing the psychological categories into purer sub-groups.

The same strategy can be applied to each of the mental illnesses. Adults diagnosed with social anxiety are a little more likely than the average person to have a tall, thin body build, a high and minimally variable heart rate, and a narrow face. Discovery of the genes that contribute to these properties would allow investigators to parse this disorder into its purer sub-types. The current mental illness categories resemble the seventeenth-century medical categories headache, fatigue, and cramps, each of which has multiple causes.

An indifference to the contribution of a person’s experiences and local circumstances to their psychological properties is yet another reason for the failure to discover robust links to genes. Adults who possess the genes that contribute to posttraumatic stress disorder will remain free of these symptoms as long as they are lucky enough to avoid the serious stressors of combat, rape, or a natural disaster. The genes alone cannot generate this disorder.

About one-third of Caucasian children inherit a set of genes that biases them to be relaxed, minimally irritable infants, sociable, fearless toddlers, and confident, minimally anxious adolescents. It is believed that the chemical products of these genes render the amygdala resistant to activation by everyday threats that make some anxious, tense, or guilty. A person born with these genes and raised by affectionate parents who promote academic excellence and socialize the regulation of aggression and disobedience is likely to be a popular child who is a leader with peers and an adult with a satisfying career requiring challenge and some risky decisions. A child with the same genes raised by indifferent parents who did not encourage academic achievement and failed to suppress aggressive behavior is at risk for a life marked by an unsatisfying job and/or an anti-social life style. These two children inherited genes that made it easier for them to take risks without feeling anxious. Their life histories determined whether this property led to a career as an accomplished test pilot or an incarcerated criminal. Genes, like the menu at a restaurant, propose a variety of possibilities; life experiences function like each of the guests who select one outcome from the larger set.

The vulnerability of genes to being altered by outside events is yet another reason why links between genes and a behavior or mood have been hard to verify. Famine, stress, diet, and infection, along with a host of other events, have the power to silence a gene, and, therefore, remove its influence, often temporarily, without changing the sequence of the bases that define the gene. This extraordinary malleability to outside events is rare in non-living matter. A boulder on a beach is exposed to the sea, drifting sand, and birds resting on its surface. It may lose some mass over many years but the properties of its electrons, protons, and neutrons are not altered by these events.

The inability to find persuasive associations between genes and psychological phenomena is also due to the fact that the consequences of a gene, or set of genes, is moderated by all the other genes in that person’s genome. As a result, two individuals who possess a gene known to increase the concentration of a molecule that induces a mood of relaxation might develop different moods because their total genomes were not the same. Even the parental origin of the gene, that is, the mother or father, can affect the outcome. Each child inherits one set of chromosomes from each parent. A gene linked to a specific metabolic outcome creates distinctive symptoms depending on whether that gene was inherited from the mother or the father, even though the structure of the gene is unchanged. A diamond has the same features whether it was inherited from the mother or the father.

All these conditions make the task of finding robust links between genes and mental events far more difficult than the scientists who chose to engage in this mission imagined. Because some individuals with a gene, or genes, that are known to be an important contributor to a disease do not have the expected symptoms of the illness, and most disease symptoms can be the result of different genes, it will be a long time before the hopes of nailing down firm associations between mental properties and genes will be satisfied.

It is useful to remember that, at the moment, the best predictor of who will develop diabetes, stroke, heart attack, depression, anxiety, an addiction, or display violent behavior or fail to graduate high school is the social class of the family of rearing, not any collection of genes. By contrast, genes, not the class of rearing, are the best predictor of sensory acuity, speed of a motor response, body type, intrusive bodily sensations, and the bias to be maximally alert in the early morning or the evening. Perhaps scientists should spend more time looking for links to these outcomes. This conclusion is not meant to imply that genes are unimportant contributors to mental illness or personality. Quite the contrary, it is intended to argue that scientists will have to examine genes, life histories, and a larger variety of properties together in order to make the discoveries they pursue with extraordinary skill and patience.

No one denies the importance of genes. But the propaganda that awards them most of the power over psychological outcomes misleads the public and seduces some young scientists to initiate research that ignores the conditions genes must collaborate with in order to generate the moods and acts we care most about. It is true that without genes we would be nothing. But because there are no genes that code for water and air, it is equally true that we would be nothing if we were only genes.

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