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The Cone of My Incompetence

Here's an excerpt from my new book, The Cone of My Incompetence: How My Genes Keep Me Down:

From an early age, I realized I was different.

Some people have natural gifts like energy, drive, charisma, motivation, calm under pressure, willpower, self-discipline and resilience. They’re lucky to be born with such rare and highly valued traits.

But I’m not so lucky. I lack natural potential and talent. And no amount of practice can change that.

I call it The Cone of My Incompetence.

My Cone determines my needs, wants, interests, fears, obsessions and desires. It resides deep in my subconscious brain, constructed by my DNA.

My Cone keeps me down. Managing people just makes me nervous. Power hierarchies leave me cold. Unless rallied by a natural leader, I’m a lazy sloth. I’m a natural born follower. A promotion is not in my DNA.

Those born with natural gifts are rewarded with lavish salaries, bonuses, perks, and promotions. But I’m not.

I never chose this Cone. It’s not something I have. It’s who I am.

And it’s not fair.

Here's another description from Amazon.com:

Frustrated by his own lack of talent and natural gifts, the author questions whether elite meritocrats--corporate executives, doctors, lawyers, lobbyists, bankers--who are lucky to be born with rare character traits like self-confidence, energy, resilience, and drive, truly deserve their enormous pay packages, bonuses and perks

You can order it here.

The buzz on genes and behavior

Researchers have long worried that correlating genes and behavior was "too complex to fathom, because so many factors can act together to regulate behavior."

Now new research shows how a few "master genes" can switch on and off complex behaviors, at least in bees.  

Researchers found that "naturally occurring behaviors are under the influence of discrete regulatory networks in the brain ... there is a close relationship between changes in gene expression ... and behavior."

They also found "a high degree of modularity in the regulation of genes and behavior, with distinct behavioral states".  Words like "discrete" and "modular" are important, as they show that complex networks created by genes can be controlled and achieve a steady state.

"The team focused their analysis on ... genes implicated in ... foraging, such as scouting for flowers ... maturation, ... and aggression, or hive defense."

Look for more informatio on the BeeSpace project which developed "a catalog of genes that turn on or off in the bee brain in response to social cues, environmental changes or as a result of hereditary factors."

Social behavior genes

Everyone has the same 23,000 genes, which we all share.  But most genes come in different variants or flavors, known as alleles.

For example, everyone has a copy of the GTF2I gene, which controls the activity of many other genes. But children born with a one of the variants of the GTF2I gene have a strong desire to make eye contact and seek social interactions.  Scientists speculate that GTF2I "might regulate signal pathways determining the structure and function of the brain or the production of neurohormones".

How can differences in the GTF2I gene make one person outgoing and sociable, and another shy and fearing eye contact?  It's a two-step process: trained recognition, and innate predisposition toward the recognized scenario. 

First, one set of genes establishes the brain's ability to train itself to "recognize" certain aspects of the environment (e.g. to perceive human faces and eyes).  Then, another set of genes (triggered by the GTF2I gene) develops the brain's circuitry to exploit this recognition ability, to predispose our reaction when the situation is detected. If you have one variant of the GTF2I gene, you'll be attracted to the human faces you've been (innately) trained to recognize.  If you have a different variant, you'll fear human interaction and seek to avoid it.

Genes such as GTF2I simply act as "master switches" to enable one or the other trait to be implemented in the brain, probably in the amygdala or basal ganglia regions.  But someone who's shy doesn't inherit an entirely different set of genes. We all share the same genes, and these genes differ by less than 1%, which implies that we each possess all the genes that construct the brain to be either shy or outgoing.

This begs the question: If I'm shy, can I simply replace my GTF2I gene with a different variant?  The answer depends on whether GTF2I is a "development gene" or "signaling gene".  Brain development genes are likely to be irreversible, since they alter the physical layout of the brain, so replacing them after you're born would have no effect. But signaling genes (or their products) are more easily intercepted by drugs.  This is how anti-depressant drugs work, and it's also a known side-effect of certain medications for Parkinson's disease that strangely increase your urge to gamble (implying that gambling behavior is innate - hardcoded in the brain - and triggered by signaling genes that can be intercepted by drugs).

If GTF2I is a "signaling gene" there's hope that drugs can be developed to transform us into ultra-sociable, eye-contact seeking, trusting individuals, with a good ability to recall names.  If not, then only a genetic change (prior to conception) can alter our personality to be more outgoing.

How does the brain work?

Our brain is built by our genes.  And since no two people have exactly the same genes, it follows that no two people have the same brain structure.  (Even identical twins have so-called "epigenetic" differences.)

Personality differences between people thus emanate from differences in their brain structure. Scientists are now discovering, for example, specific gene variants that may alter our social behavior.

But what do these brain genes actually do?  We can find the answer by comparing someone with selective mutism (a form of social anxiety) with someone who doesn't have that affliction.  Selective mutism is a genetic condition that renders someone completely mute in public, even as they are normally talkative at home with their family.

Genetic differences between these two individuals has a dramatic effect on their personality.  Whereas everyone has genes that are responsible for building "specialized modules" in their brain (for example, we all have a brain module that can recognize when we're in a public setting), the brain response to this recognized scenario is what differs between the two subjects.  Different outcomes are triggered based on their individual gene variants.

So not only are genes are responsible for building very specific "situation detectors" and "triggers" and "response modules" in our brain.  These modules may have a different "logic" or algorithms depending on which gene variant we carry.  Politicians, for example, are usually energized by crowds and public settings, but someone with Selective Mutism can't choose to be motivated by crowds.

Innate brain modules can also be triggered by drugs.  Indeed that's often how our hormones work, by initiating our primal behaviors, by acting as intermediaries between our "recognizer" brain modules and our "response" brain modules.

Maternal Instinct Is Hard-Wired Into the Brain

Tara Parker-Pope wrote an interesting blog entry in the New York Times Health section, about a scientific study on how mothers respond to their children's cries, because of the innate wiring of the mothers' brain.

The article was interesting, but I was captivated by the reader comments, which were overwhelmingly negative, but also strangely off-base, as if the readers themselves weren't hard-wired to understand their own human nature.

Some comments made the point that if a trait isn't constant and unchanging, it can't be hard-wired. This is silly.  Human development occurs over time, but it's still innate.  For example, women develop breasts many years after they're born, but breast development is obviously innate.  Also, women have their periods sometimes (not all the time), so periodicity can also be programmed into the genes.

Furthermore, some social behaviors, such as "selective mutism", are innate, even as their development relies on experience.  You must first learn what a human face looks like (experience), before you can have an innate reaction (fear, shyness) to faces. But even if a trait requires "tuning" in the context of the environment, that doesn't make it any less innate.  The learning of faces is retained in the brain in a location well-known to the genes a priori, so the genes can exploit this ability later.  Seeing faces can make us shy, because our genes built the innate circuitry to recognize and remember faces in the first place.

The point is... the definition of a "hard wired" trait is not that something is fixed and unchanging from birth.  It's simply a trait whose development is programmed (by our genes) to unfold in the context of (expected) environmental scenarios.

Brain genes

The brain is a three-dimensional form, weighing about 3 pounds in adults (less than a pound in newborns).   Each of the 100 billion cells (called "neurons") in our brain connects with thousands of other neurons.  [There are also another 900 billion or so "supporting cells" in the brain, but we'll ignore those for now].  All told, there are around 1 quadrillion (10¹⁵) connections between neurons (called "synapses") in the entire brain, where activity happens to create the mind.

So the development of the brain is largely a problem of how to connect 100 billion neurons using 1 quadrillion synapses, so that the brain can operate, consciousness can emerge, signals can be processed, memories can form, and responses can be effected (free choices can be made?)

About 6,000 of our genes seem to be active only in the brain; genes (or gene-produced proteins) like Robo which induce neurons to grow in specific directions inside the skull, and others that allow them to recognize friendly neurons and cling to them (making a synapse), and then allow signals to be transmitted across those synapses.  Many specialized proteins (such as Reelin) help in the formation of synapses once two neurons find each other and “dock” together.  Reelin also helps the brain develop its characteristic six-layer structure.

Cadherins are sticky molecules that guide neurons as they migrate inside the skull, to find their permanent position.  Think of them like Spiderman climbing a building, using a sticky substance to cling and move against gravity and friction, propelling against other neurons until the right one is found with which to form a more permanent synaptic connection.

The Emx family of genes is involved in establishing the identity of certain regions in the brain.  The brain is full of specialized areas (vision, speech, planning, etc) which are set up in the course of development.  The Eph family of genes help lay out the basic topography map of the brain, by setting up a chemical gradient (like the latitude and longitude on a GPS device) which allows migrating neurons to find their home.  The Hox genes also help to establish basic layouts of the brain and body. Other examples of "brain genes" include Pax6, important for the formation of the eye, and NMDA receptors which seem to play an important role in establishing memories when the activity of two neurons coincide closely in time.

Since genes largely function to create proteins, I’ll use genes and proteins fairly interchangeably.  However, some genes can code for multiple proteins depending on the context, so it’s not as simple as “one gene = one protein”.  The FGF8 gene (fibroblast growth factor 8), for example, can be sliced and diced in different ways, leading to the production of different proteins (depending on context).  Those proteins are also responsible for laying out some of the gross anatomy of the brain.

Once neurons have made their specific connections together in the course of their development, those same synapses can be used not only to send signals from one neuron to other.  Synapses are not truly connections - but gaps - between neurons into which signalling chemicals are injected.  Usually, those chemicals are neurotransmitters (like serotonin) which are used to send signals from one neuron to the next across the synaptic gap.  But hormones and other compounds (like anti-depressants) in the bloodstream are also able to influence the signal of many synapses (and other receptors), at a global level.

For example, vasopressin is a hormone released by the pituitary, that can affect social behavior.  The most promiscuous male prairie voles, for example, have fewer vasopressin (V1a) receptors in a specific region of their forebrain (ventral pallidum region).  Artificially introducing more vasopressin receptors into their brain immediately makes them seek monogamous relationships.

I've often thought that the strategic placement of hormone receptors throughout the brain and body during development (like the placement of troops on a battlefield) is much more interesting than the hormone itself (or "command from the general"), which is really just a molecule (or, to follow the analogy, a single word -- "Charge!").  The signal simply triggers a response that was already planned, practiced and ready. In simple organisms like the “sea slug”, entire complex behaviors can be triggered by a single hormone, such as the ELH (egg-laying hormone), due to the way receptors have been set up in advance in the synapses of its neurons.

I've described some of the genes that are active in the development of the brain, but I haven't begun to describe the variants of some of those genes.  Obviously, if two people don't have exactly the same version of the NMDA receptor, perhaps one of them would have a better ability to recall facts.  This is obviously an interesting area for future exploration under the subject of "genetic variation and social fairness".

Reductionism

A recent article in the journal Science announced a stunning and exciting new finding:

individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity

OK, maybe it's not all that exciting at first glance!  Science is full of reductionist jargon, and scientists don't appreciate it when you try to draw abstract conclusions based on the narrow experimental evidence.  In any case, here's my interpretation of the article:

Everyone has the same 20,000 genes.  One of those genes is called SLC6A4 (previously called 5-HTT).  However, different people have different versions of that gene, the long variant and the short variant.  [If you really want to know the technical details, the long variant has 16 repeats of a 44 letter DNA sequence, and the short version has 14 deletions of that repeated sequence, called a "copy number variation" (CNV)]

Technically, the genetic difference lies in the so-called promoter region (or "on switch") just in front of the gene, not in the gene itself.  But in any case, it's all DNA.  Specialized proteins (called "transcription factors") latch onto this promoter region, looking very much like highway paving machines.  The promoter region (short or long variety) acts as the construction supervisor, telling the machine how much protein to make based on the gene template (or how much pavement to lay down).

It turns out that people with the short version of the gene have a more active amygdala, a structure in the brain (see the red area in the top picture) involved in processing negative emotions, and thus they have a greater response to fearful stimuli than people with the longer variant of the gene.  Your genes at work!

Correlation is not the same as causation, of course.  For example, people with the HLA-A1 gene variant tend to use chopsticks, but that doesn't mean HLA-A1 causes the use of chopsticks.  It's simply a more common gene variant in Asians than Caucasians, and Asians tend to use chopsticks.  If you wanted to prove that HLA-A1 was the "chopstick gene", you would have to show (among other things) the contrapositive, that Asians who don't use chopsticks also don't have the HLA-A1 gene variant.

Genes: Blueprints or Recipes?

Scientists are often asked whether genes act as blueprints, or instead as recipes, for human development.  According to NYU Professor Gary Marcus, genes are not blueprints, because there are simply not enough genes to describe exactly how each of our billions of cells should fit together.  Rather, he says, genes are part of "self-regulating recipes" whereby gene activity is designed to respond to environmental cues in the course of natural development.

Whereas I'm sympathetic to this line of reasoning, I still like the blueprint analogy, because it provides fewer and simpler variables for:

1. Transmission of discrete traits
2. Evolutionary selection

Human society is filled with specialized actors.  Some are brave, some are smart, some are leaders, some are followers.  The distribution of these traits is unevenly balanced, in order for society to run "smoothly".  (Smoothness and fairness are, of course, two different things).  In order for these traits to be balanced, bravery, intelligence, and leadership ability must be regulated by simple on-off switches in the genome, otherwise it would be too complicated to allocate and distribute these traits in specified proportions across society.

In other words, while there may be thousands of genes involved in specifying the "recipe" for a leader (how s/he reacts, responds, displays emotions, etc), there must be a fairly small number of genes that act as the blueprint or master switch, to enable one recipe over another.  One only need to do an online search for "single gene responsible for" and "scientists shocked/perplexed/amazed" to find genes like Bax that act as master switches.

Also, evolution of species would be more rapid (in the face of changing environments) if selection were made among a small number of variables.  For example, the genes responsible for the development of beaks on Darwin's finches may act as recipes, but behind these must exist master genes for selection pressure to quickly act upon.

The nesting instinct

According to PregnancyWeekly, around the fifth month of pregnancy, a woman develops a set of nesting behaviors (cleaning house, etc) that on the surface seem quite rational (preparing for the new baby, etc).

But in reality, the behaviors are a "primal instinct" (like "birds making their nests"), not a rational choice based on a logical deduction (i.e. "I need to clean up to ensure the health and safety of the baby").  We know this, because the woman's behaviors themselves are not rational, and are often counterproductive:

Women have reported throwing away perfectly good sheets and towels because they felt the strong need to have "brand new, clean" sheets and towels in their home. They have also reported doing things like taking apart the knobs on kitchen cupboards, just so they could disinfect the screws attached to the knobs. Women have discussed taking on cleaning their entire house, armed with a toothbrush ... Being preoccupied with ant killing, squishing them one at a time for weeks on end. Packing and unpacking the labor bag 50 times. Cleaning the kitchen cupboards and organizing everything by size to the point that you make sure the silverware patterns match when it's stacked in the cutlery drawer. Sorting the baby's clothes over and over again is a favorite theme. Taking them out of the drawers and re-folding them, putting them away and doing it over and over again.

Clearly, many of these behaviors are obsessive-compulsive, and may actually jeopardize the baby's health by putting stress on the mother.  Because it's not rational, it must be instinctive.  But how do instincts work?  Some of our genes must develop the circuitry in a woman's brain to make the instinct function properly:

1. Genes develop the brain circuitry to motivate women to compusively "clean up" and organize
2. Other genes create an "on switch" that allow simple pregnancy hormones to activate the behavior at the appropriate time

A Nobel prize awaits the scientist who can explain how instincts are manifest in human genes and neurons in the brain.

DNA and social behavior

There is some evidence that human personality differences may be explained by differences in our so- called "junk DNA" (i.e. the 95% of our DNA that's not used to make protein), according to a study done by researchers at the Yerkes Primate Research Center and the Center for Behavioral Neuroscience.

[The technical term "microsatellite length", used below, refers to how often a subset of the gene repeats itself.  Each unique number of repeats (1, 2, 3... etc) describes a unique "gene variant" (variant 1, variant 2, variant 3, etc).]

"This is the first study to demonstrate a link between, gene expression patterns in the brain and social behavior across several species," said researcher Larry Young. "Because a significant portion of the human genome consists of junk DNA and due to the way microsatellite DNA expands and contracts over time, microsatellites may represent a previously unknown factor in social diversity."

Genes and Personality

A recent article in Psychology Today describes the reaction of George Washington University psychiatrist David Reiss, after reviewing the results from his study on genetics and personality in child development.

"It's a radical revision of contemporary theories of child development," says Reiss. "I can't even describe what a paradigm shift it is."

According to the article, "parents appear to have relatively little effect on how children turn out, once genetic influences are accounted for ... Genetic influences are largely responsible for how "adjusted" kids are: how well they do in school, how they get along with their peers, whether they engage in dangerous or delinquent behavior."

The genetics of heroism

David Karnes, the marine who found two World Trade Center survivors, seems "a bit crazy brave", according to an article in Slate magazine.  "You'd have to be slightly abnormal—abnormally selfless, abnormally patriotic—to do what he did. And some of the same qualities that led Karnes to make himself a hero when it counted may make him less perfect" in other situations.

What would motivate someone to leave the safety of his home (in another state, no less), and rush to the scene of disaster and human suffering?  You could say it was his training as a marine, and indeed, marine training is harsh.  It trains a man to obey orders (for those men who are pre-disposed and excited to be part of a strict power hierarchy).  But no amount of training can make you actually feel patriotic. Emotions and motivations and feelings can't be trained; they can only be invoked and incited.  Therefore, they must be innate.

It does seem a little insulting to explain bravery as innate and genetic, until you realize that "genes are not something you have; genes are who you are".  Karnes felt a deep sense of duty, because of who he is.  He became a marine in the first place because of who he is. You can't teach feelings, and so feelings must come from somewhere else -- the genes.

But we humans are not built to talk about each other this way.  It seems somewhat demeaning.  We want to appreciate people for who they are.  But that is the same thing as admiring their genes.  I'm just saying that if you had different genes, you would make different choices, of your own free will.

The Pseudo-Science of Siblings

Time Magazine, in its eternal struggle to show that genetics is less important than environment, recently published an article on how our siblings affect how we turn out.

It’s interesting that Time now concedes that “any parent can tell you that each child comes from the womb with an individual temperament that seems preloaded” at birth. 

Yet according to Time, our siblings affect our innate temperament, “moderating it, challenging it, annealing it, wounding it,” so “what we're left with after 10 or 20 or 50 years is quite different from what we started out with”.

So what do we start out with?  We start with an innate desire to train ourselves to develop personality traits.  These traits then naturally develop over time, due to the experience we seek out.  For example, Napoleon wasn't born knowing how to command men, just the burning desire to learn this from whatever source he could find.

In any case, what can we say with certainty about siblings?  We know that adolescents spend 10-17 hours a week with their siblings, and younger children spend even more of their time with siblings (33%).  Over the course of evolution, our siblings were a constant part of our environment. 

So as our genes evolved, they could safely assume that the environment would always contain siblings.  That assumption is built in to our form.  If our genes wanted to tune our development, they could assume that siblings were there to help with the tuning.  For example, someone born with natural athletic ability (and innate motivation to spend time training) still needs to seek a coach or partner to perform the training.  It's the "desire to seek the training" that's innate, which naturally leads to the development of the skill or trait.  If our siblings can provide this, all the better.

If we are born leaders, we still need to fine-tune our specific leadership behaviors.  Our siblings don’t make us leaders if we’re not already born with that predisposition.

Does the picture get cloudy, due to genetic branching behavior?  Do some siblings observe each other and deliberately acquire opposing personalities through “de-identification”?   Such a capability to observe and differentiate would have to exist in our genetic nature (because why would children choose to do so for no reason?)  Or do those children only appear to differentiate, whereas they were innately different all along?

What Time Magazine is saying may be true, but it is trivial.  If someone is born with a tendency to be manipulative, they still need to rehearse and perfect and “find strategies” for their craft, with their siblings as props.  That doesn’t mean their siblings have any effect on their basic personality.  Our genes have an expectation that our siblings are present, to fine-tune our innate personality traits.

Genetics and violence

A recent article describes how some people (with a specific gene variant called "MAO-A") have a stronger reaction when "shown pictures of angry or fearful faces". 

"MAO-A breaks down ... neurotransmitters [in the brain] so that they no longer exert their effects on the nervous system".

"Researchers showed that males with lower levels were more likely to develop antisocial behavior in response to being maltreated during childhood [perhaps] because they are less able to reduce their neurotransmitter levels ... after a stressful event, limiting their ability to control aggressive impulses." 

In other words, people will react differently to the same environment, due to variations in their genes.

Why do identical twins differ?

Why do identical twins (who possess the same genes) differ from each other?  New studies show that:

Human cells have tens of thousands of genes in them, each with its own job, such as producing energy. But only certain genes are active at any given time or in any cell type while the rest are appropriately dormant — a grand orchestration that adds up to a smooth-running life.

The new research, led by Mario Fraga and Manel Esteller of the Spanish National Cancer Center in Madrid, focused on two biological mechanisms that influence gene activity. In one, called DNA methylation, enzymes inside a cell attach a minuscule molecular decoration to a gene, deactivating that gene. In the other, called histone acetylation, a dormant gene is made active again.

These altered genetic settings can last a lifetime and can be important if, say, the gene turned off is one that protects against cancer.

In the new work, described in the current issue of Proceedings of the National Academy of Sciences, researchers measured the extent to which twins of various ages, from 3 to 74, differed in the number and variety of genes that had been either turned on or shut down by epigenetic processes. They found young twins had almost identical epigenetic profiles but that with age their profiles became more and more divergent.

In a finding that scientists said was particularly groundbreaking, the epigenetic profiles of twins who had been raised apart or had especially different life experiences — including nutritional habits, history of illness, physical activity, and use of tobacco, alcohol and drugs — differed more than those who had lived together longer or shared similar environments and experiences.

Small epigenetic events before birth probably account for many of the minor distinguishing differences in the appearance, personality and general health of young twins, Esteller said, and a lifetime of further epigenetic changes gradually increases individuality.

Social behavior genes

A recent article in the New York Times discusses the 30 or so genes (discovered so far) that seem to regulate social behavior in animals.

Genes have been found to regulate courtship behavior in fruit flies, as well as mating behavior in mice.  Most interesting, though, is how "social behavior genes present a particular puzzle since they involve neural circuits in the brain, often set off by some environmental cue to which the animal responds".  Genes can harness the higher brain to have their effect.

What aspects of personality are innate?

The following 5 aspects of personality (OCEAN for short) are often thought to have some innate qualities:

1. Openness to Experience/Intellect -High scorers tend to be original, creative, curious, complex; Low scorers tend to be conventional, down to earth, narrow interests, uncreative
2. Conscientiousness - High scorers tend to be reliable, well-organized, self-disciplined, careful; Low scorers tend to be disorganized, undependable, negligent
3. Extraversion -High scorers tend to be sociable, friendly, fun loving, talkative; Low scorers tend to be introverted, reserved, inhibited, quiet
4. Agreeableness -High scorers tend to be good natured, sympathetic, forgiving, courteous;Low scorers tend to be irritable, rude, vengeful, callous
5. Neuroticism - High scorers tend to be nervous, high-strung, insecure, worrying;Low scorers tend to be calm, relaxed, secure, hardy