Philosophy of Genetics

Genes and antisocial behavior

According to a recent scientific article, a specific variant of the COMT gene can predict whether a child will develop "early-onset antisocial behavior accompanied by attention-deficit/hyperactivity disorder".

I'm not saying that this is the gene variant that leads one to become a sociopath.  Yet, I can't help wondering whether the process of evolution intended for some of us to be anti-social.  People with anti-social tendencies could be the ones who inspire wars.  Since death is the mechanism by which natural selection occurs, having more battles would certainly speed the process of evolution.

Genes and brain size

Science magazine reports that "two genes involved in determining the size of the human brain have undergone substantial evolution" as recently as 5,800 years ago.  Those two genes are microcephalin and ASPM.  When those genes are completely switched off, they lead to "microcephaly", or small head.

Another gene, GPR56, appears to affect mainly the development of the frontal cortex.  According to Wikipedia, the "frontal lobes have been found to play a part in impulse control, judgment, language, memory, motor function, problem solving, sexual behavior, socialization and spontaneity. Frontal lobes assist in planning, coordinating, controlling and executing behavior."

With this knowledge, scientists investigated whether different variants of the genes were responsible for different brain sizes among people.  According to the New York Times:

About 70 percent of people in most European and East Asian populations carry [a specific variant of the microcephalin] gene, but it is much rarer in most sub-Saharan Africans.

With the other gene, ASPM, a new [variant of the gene] emerged 14,100 to 500 years ago, the researchers favoring a midway date of 5,800 years. The allele has attained a frequency of about 50 percent in populations of the Middle East and Europe, is less common in East Asia, and is found at low frequency in some sub-Saharan Africa peoples.

The Chicago team suggests that the new microcephalin [gene variant] may have arisen in Eurasia or as the first modern humans emigrated from Africa some 50,000 years ago. They note that the ASPM [variant] emerged about the same time as the spread of agriculture in the Middle East 10,000 years ago and the emergence of the civilizations of the Middle East some 5,000 years ago, but say that any connection is not yet clear.

Four Types of Genetic Variation

We all have variants of the same 20,000 genes.  A recent article lists four types of genetic variations:

1) Single "letter" variations (called SNPs -- these often get inherited together in blocks called haplotypes), 2) additions or deletions (InDels) of DNA units, 3) repetitions like those that underlie forensic DNA tests, and 4) flipping of large segments of DNA within a chromosome.

Some things to keep in mind, however.  At the level of philosophy, it's more important to express the gene variation in terms of how much information is being stored in the genes, and how many different branching points and scenarios can be represented.  The physical manifestation of variation in the DNA is somewhat irrelevant, as long as the information is there.

For example, we each have a number of repeating units (of 48 or 120 DNA letters, or bases) in our DRD4 gene, which may be responsible for novelty-seeking behavior.  The number of repeats (3, 5, 7... etc) seems to encode the amount of risk-taking you are comfortable with.

Gene Chips

Most people don't know it yet, but the year 2005 has been a turning point in affordability of measuring genetic variation between people.  The new Affymetrix gene chip can take a sample of your blood and discover 100,000 genetic differences between you and your neighbor for under $5,000.  That price keeps coming down every year, and pretty soon we're all going to be able to order a report on our genetic variations for the price of, well, a home computer.

We don't yet know what all the genetic differences mean.  But any day now, the ubiquity of genetic sequencing will change our world dramatically, the same way computers changed our lives when Bill Gates and Steve Jobs came on the scene in the 1970's, and especially, the early 1980's.  Perhaps gene chips will double in power every 24 months, as Gordon Moore predicted about computer chips. 

When that happens, it will be a whole new world.  Festering social debates will be re-opened, like cold cases re-opened by new DNA evidence.  Politicians will be forced to talk about genetic differences when they make policy (and the Democratic Party, which doesn't believe any of this, will probably cease to exist).  Biographers will have to consider alternative (genetic) theories about human behavior when they write their books.  We humans will opt to change ourselves, and adopt strange new genetic forms.  We will live in interesting times.

Everyone has the genes for every human trait, but an "on switch" for very few

We all have the same "genes", which are 99.9% similar to everyone else's.  Shy people and outgoing people have the same basic genes, but their personality traits are different.  How can that be?

It's important to understand that not all of our genes are put to use.  A shy person may have their "outgoing genes" permanently switched off by a few "master genes".  Most of the 0.1% difference among humans can be found in the genes that act as master keys.

This implies that everyone carries all the genes for all human traits (including the capacity to be a psychopath, which is simply a more rare innate trait, but excluding male/female traits, since women don't have a Y chromosome). 

It's easy to see why this would be true.  If shy people had to inherit hundreds of unique (specialized) shyness genes as a package, that trait would quickly deteriorate when the genes were passed down from parent to child.  Having children tends to remix the genes, so keeping genes together (and keeping them separate from the genes for outgoing traits) would be impossible.

Genetic Variation and how we respond to drug treatments

Drugs don't always work for everyone.  Often, having a certain genetic variation means you won't respond to a drug.  For example, a certain breast cancer drug only works for 25% of women.  So first, a woman must take a genetic test to see if she has the specific gene variant that responds to the drug.

The PharmGKB is an integrated resource about how variation in human genes leads to variation in our response to drugs. 

Genographic Project

According to the Genographic Project's website:

We are all related—descended from a common African ancestor who lived only 60,000 years ago.  When DNA is passed from one generation to the next, most of it is recombined by the processes that give each of us our individuality.

But some parts of the DNA chain remain largely intact through the generations, altered only occasionally by mutations which become "genetic markers." These markers allow geneticists like Spencer Wells to trace our common evolutionary timeline back through the ages. 

Different populations carry distinct markers. Following them through the generations reveals a genetic tree on which today's many diverse branches may be followed ever backward to their common African root.

That's why the Genographic Project has established ten research laboratories around the globe. Scientists are visiting Earth's remote regions in a comprehensive effort to complete the planet's genetic atlas.

HapMap - Finding the top 300,000 human genetic differences

In a recent article, Francis Collins, one of the leaders of the Human Genome Project, proclaimed that "the HapMap is generating a gold-standard set of [gene] variants".

So, what is this new HapMap project?  It's an international $100 million project slated for completion in 2005, and funded in the U.S. by the National Institutes of Health.  The goal of HapMap is to find many of the gene variations among humans that make us different from each other.

The HapMap project is a follow-on to the Human Genome Project.  That project, which completed a few years ago, identified the 20,000 gene locations we all share, but not the gene variants at each location.  Essentially, the Human Genome Project identified the genes of only one person (Craig Venter), a healthy, white, male, high-IQ, extroverted caucasian.

The HapMap project acknowledges that we all share 99.9% of the same genetic material, but since we all have 20,000 genes comprising 3 billion "DNA letters", having a 0.1% genetic difference translates to 3 million variations between people.  (Remember that two keys need have only 1 difference in order to open two different locks!)

The HapMap project found that "only" 300,000 or so of these differences comprise the most important set, responsible for differences in disease susceptibility, personality differences, etc.  When those differences are measured, and correlated with the results of questionnaires, we can find out which genetic difference leads to which effect.

Hot Button Issue: For example, if a significant number people who are found to have gene variant XYZ answer "yes" when asked if they have ever committed a crime, that gene variant may be responsible for a lower threshold to anger and aggressive behavior.

There's a gene for that!

Many people say the human body and mind are so complex, there is no way to understand them in terms of simple causes.  But there are two common examples where a single "switch" can control complex behavior or development:

• Broadcast commands using hormones
• Master genes

Broadcast commands using hormones
One way to send a signal throughout the body is to release a hormone into the bloodstream. Throughout the body, "troops" (i.e. hormones receptors) are listening, waiting, and trained to respond to this "command", like soldiers with radio receivers waiting to hear an order. 

Releasing the hormone (often done by the brain) is a singular act.  The complex part (having receptors pre-arranged throughout the body that are specially trained to respond to the hormone) was established well in advance, like soldiers laying in wait across a battlefield.  They listen for commands (with their detectors), and ignore any other commands (i.e. other hormones) for which they were no trained to respond.  A single command (or signal) like "division 1, charge!" sets in motion a complex, coordinated behavior.

Setting up a complex system of receptors (ahead of time) in diverse locations allows a simple signal to trigger a complex response.

Master genes
Some genes are the generals of our development.  The SRY gene, for example, simply issues a single command for the developing body to develop into a male.  The command is broadcast for a few hours only - before birth (as studied in mice) - then switches off forever.

The SRY master switch triggers a cascade of other genetic activity throughout the body, the same way that a general's order may have far-reaching consequences.  In other words, the simplicity of the command is made possible by the prior "training" of the troups.  Even though male development (or commanding an army) is an extremely complex process, it can be conducted using simple commands.

The groundwork was laid in advance, and it's interesting that the enactors must have pre-established, built-in "receptors" to allow them to hear the command.  The strategic distribution of the receptors (soldiers), and their cascade of activity once activated, are the truly complex aspects of this.  But the general (hormone, master gene) is the one who gets the glory of launching the battle.

It's not of the amount of genetic difference that matters

It's true that humans share over 99% of the same DNA with each other. But that statistic is not really very meaningful. Think of two keys to the same brand of automobile. Both keys appear almost identical, except for a slight difference in 1% of their metal. Perhaps one key has a slight ridge where the other doesn't. But this small difference has a dramatic effect, when trying to open the door or start the car. One key works, the other doesn't.

We humans each have 3,000,000,000 letters in our genetic code, and we only differ among each other by 0.1% of those pieces.  That doesn't sound like a lot, but it still means we have 3,000,000 differences among us.  That's enough to determine differences in personality and hair color and all the rest.

We don't have 20,000 genes; We have 20,000 locations that get filled with gene variants

Scientists have discovered (to date) that humans have over 20,000 gene locations (also called loci) into which we receive gene variants (also called "alleles" or "polymorphisms").  Think of it as a set of 20,000 post office boxes in a long row.  Into each location is deposited a gene package from our mother and one from our father.  The gene packages in a particular location (say, mailbox number "GRM3") are fairly similar, but not identical; they are unique gene variants which explain human diversity.

Geneticists identify gene "locations" by a Hugo name, and typically refer to the specific contents of that gene (i.e. the variant) by letter (e.g. variant A, variant B, variant C..) or some other name.

For example, everyone has a variant of the GRM3 gene - but if you receive the 'A' variant you have a greater chance of developing Schizophrenia.

Do gene variants serve a purpose when they are responsible causing diseases?  It's hard to speculate.  I believe there may be something specific that schizophrenics contribute to society (maybe they help rescue society from disaster once every 1,000 years) that encourages the variants to remain in the collective genome of society, even though it's a terrible price to pay for those afflicted.