The looming crisis in human genetics

THE ECONOMIST
Nov 13th 2009
From The World in 2010 print edition
Full article: http://www.economist.com/displaystory.cfm?story_id=14742737

By Geoffrey Miller
University of New Mexico

In a nutshell: the new genetics will reveal much less than hoped about how to cure disease, and much more than feared about human evolution and inequality, including genetic differences between classes, ethnicities and races....

Dozens of papers will report specific genes associated with almost every imaginable trait—intelligence, personality, religiosity, sexuality, longevity, economic risk-taking, consumer preferences, leisure interests and political attitudes. The data are already collected, with DNA samples from large populations already measured for these traits....

When sequencing costs drop within a few years below $1,000 per genome, researchers in Europe, China and India will start huge projects with vast sample sizes, sophisticated bioinformatics, diverse trait measures and detailed family structures. (American bioscience will prove too politically squeamish to fund such studies.) The missing heritability problem will surely be solved sooner or later....

The trouble is, the resequencing data will reveal much more about human evolutionary history and ethnic differences than they will about disease genes. Once enough DNA is analysed around the world, science will have a panoramic view of human genetic variation across races, ethnicities and regions. We will start reconstructing a detailed family tree that links all living humans, discovering many surprises about mis-attributed paternity and covert mating between classes, castes, regions and ethnicities.

We will also identify the many genes that create physical and mental differences across populations, and we will be able to estimate when those genes arose. Some of those differences probably occurred very recently, within recorded history....

If the shift from GWAS to sequencing studies finds evidence of such politically awkward and morally perplexing facts, we can expect the usual range of ideological reactions, including nationalistic retro-racism from conservatives and outraged denial from blank-slate liberals. The few who really understand the genetics will gain a more enlightened, live-and-let-live recognition of the biodiversity within our extraordinary species—including a clearer view of likely comparative advantages between the world’s different economies.

Let’s celebrate human genetic diversity

By Bruce Lahn
Department of Human Genetics, University of Chicago

Lanny Ebenstein
Department of Economics,University of California at Santa Barbara

Nature 461, 726-728 (8 October 2009) | doi:10.1038/461726a; Published online 7 October 2009
http://www.gnxp.com/blog/Lahn.pdf

Science is finding evidence of genetic diversity among groups of people as well as among individuals. This discovery should be embraced, not feared, say Bruce T. Lahn and Lanny Ebenstein.

A growing body of data is revealing the nature of human genetic diversity at increasingly finer resolution. It is now recognized that despite the high degree of genetic similarities that bind humanity together as a species, considerable diversity exists at both individual and group levels (see box, page 728). The biological significance of these variations remains to be explored fully. But enough evidence has come to the fore to warrant the question: what if scientific data ultimately demonstrate that genetically based biological variation exists at non-trivial levels not only among individuals but also among groups? In our view, the scientific community and society at large are ill-prepared for such a possibility. We need a moral response to this question that is robust irrespective of what research uncovers about human diversity. Here, we argue for the moral position that genetic diversity, from within or among groups, should be embraced and celebrated as one of humanity’s chief assets.

The current moral position is a sort of ‘biological egalitarianism’. This dominant position emerged in recent decades largely to correct grave historical injustices, including genocide that were committed with the support of pseudo scientific understandings of group diversity. The racial-hygiene theory promoted by German geneticists Fritz Lenz, Eugene Fischer and others during the Nazi era is one notorious example of such pseudoscience. Biological egalitarianism is the view that no or almost no meaningful genetically based biological differences exist among human groups, with the exception of a few superficial traits such as skin colour. Proponents of this view seem to hope that, by promoting biological sameness, discrimination against groups or individuals will become groundless.

We believe that this position, although well intentioned, is illogical and even dangerous, as it implies that if significant group diversity were established, discrimination might thereby be justified. We reject this position. Equality of opportunity and respect for human dignity should be humankind’s common aspirations, notwithstanding human differences no matter how big or small. We also think that biological egalitarianism may not remain viable in light of the growing body of empirical data.

Many people may acknowledge the possibility of genetic diversity at the group level, but see it as a threat to social cohesion. Some scholars have even called for a halt to research into the topic or sensitive aspects of it, because of potential misuse of the information. Others will ask: if information on group diversity can be misused, why not just focus on individual differences and ignore any group variation? We strongly affirm that society must guard vigilantly against any misuse of genetic information, but we also believe that the best defence is to take a positive attitude towards diversity, including that at the group level. We argue for our position from two perspectives: first, that the understanding of group diversity can benefit research and medicine, and second, that human genetic diversity as a whole, including group diversity, greatly enriches our species.

The Young and the Neuro

By David Brooks
New York Times
October 12, 2009

...In 2001, an Internet search of the phrase “social cognitive neuroscience” yielded 53 hits. Now you get more than a million on Google. Young scholars have been drawn to this field from psychology, economics, political science and beyond in the hopes that by looking into the brain they can help settle some old arguments about how people interact.

These people study the way biology, in the form of genes, influences behavior. But they’re also trying to understand the complementary process of how social behavior changes biology. Matthew Lieberman of U.C.L.A. is doing research into what happens in the brain when people are persuaded by an argument.

Keely Muscatell, one of his doctoral students, and others presented a study in which they showed people from various social strata some images of menacing faces. People whose parents had low social status exhibited more activation in the amygdala (the busy little part of the brain involved in fear and emotion) than people from high-status families.

Mina Cikara of Princeton and others scanned the brains of Yankee and Red Sox fans as they watched baseball highlights. Neither reacted much to an Orioles-Blue Jays game, but when they saw their own team doing well, brain regions called the ventral striatum and nucleus accumbens were activated. This is a look at how tribal dominance struggles get processed inside.....

Jonathan B. Freeman of Tufts and others peered into the reward centers of the brain such as the caudate nucleus. They found that among Americans, that region was likely to be activated by dominant behavior, whereas among Japanese, it was more likely to be activated by subordinate behavior — the same region rewarding different patterns of behavior depending on culture.

All of these studies are baby steps in a long conversation, and young academics are properly circumspect about drawing broad conclusions. But eventually their work could give us a clearer picture of what we mean by fuzzy words like ‘culture.’ It could also fill a hole in our understanding of ourselves. Economists, political scientists and policy makers treat humans as ultrarational creatures because they can’t define and systematize the emotions. This work is getting us closer to that....

Many of the studies presented here concerned the way we divide people by in-group and out-group categories in as little as 170 milliseconds. The anterior cingulate cortices in American and Chinese brains activate when people see members of their own group endure pain, but they do so at much lower levels when they see members of another group enduring it. These effects may form the basis of prejudice.

But a study by Saaid A. Mendoza and David M. Amodio of New York University showed that if you give people a strategy, such as reminding them to be racially fair, it is possible to counteract those perceptions. People feel disgust toward dehumanized groups, but a study by Claire Hoogendoorn, Elizabeth Phelps and others at N.Y.U. suggests it is possible to lower disgust and the accompanying insula activity through cognitive behavioral therapy.

In other words, consciousness is too slow to see what happens inside, but it is possible to change the lenses through which we unconsciously construe the world.

Since I’m not an academic, I’m free to speculate that this work will someday give us new categories, which will replace misleading categories like ‘emotion’ and ‘reason.’ I suspect that the work will take us beyond the obsession with I.Q. and other conscious capacities and give us a firmer understanding of motivation, equilibrium, sensitivity and other unconscious capacities.

The hard sciences are interpenetrating the social sciences. This isn’t dehumanizing. It shines attention on the things poets have traditionally cared about: the power of human attachments. It may even help policy wonks someday see people as they really are.

http://www.nytimes.com/2009/10/13/opinion/13brooks.html_r=1&scp=4&sq=david%20brooks&st=cse

Unlearning Stress

August 18, 2009
BASICS
NEW YORK TIMES
Brain Is a Co-Conspirator in a Vicious Stress Loop
By NATALIE ANGIER

....[N]ow researchers have discovered that the sensation of being highly stressed can rewire the brain in ways that promote its sinister persistence.

...Reporting earlier this summer in the journal Science, Nuno Sousa of the Life and Health Sciences Research Institute at the University of Minho in Portugal and his colleagues described experiments in which chronically stressed rats lost their elastic rat cunning and instead fell back on familiar routines and rote responses, like compulsively pressing a bar for food pellets they had no intention of eating.

...[R]egions of the brain associated with executive decision-making and goal-directed behaviors had shriveled, while, conversely, brain sectors linked to habit formation had bloomed...

“Behaviors become habitual faster in stressed animals than in the controls, and worse, the stressed animals can’t shift back to goal-directed behaviors when that would be the better approach,” Dr. Sousa said. “I call this a vicious circle.”

...Robert Sapolsky, a neurobiologist who studies stress at Stanford University School of Medicine, said, “This is a great model for understanding why we end up in a rut, and then dig ourselves deeper and deeper into that rut.”

The truth is, Dr. Sapolsky said, “we’re lousy at recognizing when our normal coping mechanisms aren’t working. Our response is usually to do it five times more, instead of thinking, maybe it’s time to try something new.”

...Happily, the stress-induced changes in behavior and brain appear to be reversible.

...[W]ith only four weeks’ vacation in a supportive setting free of bullies and Tasers, the formerly stressed rats looked just like the controls, able to innovate, discriminate and lay off the bar. Atrophied synaptic connections in the decisive regions of the prefrontal cortex resprouted, while the overgrown dendritic vines of the habit-prone sensorimotor striatum retreated.

...In humans, though, the brain can think too much, extracting phantom threats from every staff meeting or high school dance, and over time the constant hyperactivation of the stress response can unbalance the entire feedback loop. Reactions that are desirable in limited, targeted quantities become hazardous in promiscuous excess. You need a spike in blood pressure if you’re going to run, to speedily deliver oxygen to your muscles. But chronically elevated blood pressure is a source of multiple medical miseries.

Why should the stressed brain be prone to habit formation? Perhaps to help shunt as many behaviors as possible over to automatic pilot, the better to focus on the crisis at hand. Yet habits can become ruts, and as the novelist Ellen Glasgow observed, “The only difference between a rut and a grave are the dimensions.”

Personality Decided At Birth, Say Scientists

New Zealand Herald

4:00AM Monday Apr 13, 2009
By Steve Connor

Pessimism and shyness is one of four categories scientists investigated.

Personality types are linked with structural differences in the brain - which could explain why one child grows up to be impulsive and outgoing while another becomes diligent and introspective.

Anatomical differences between the brains of 85 people have been measured and linked with the four main categories of personality types as defined by psychiatrists using a clinically recognised system of character evaluation.

The researchers said the brain differences are structural and can be measured as variations in the size of specific regions of the brain that appear to be linked with each of the four personality types.

Brain scans that measure differences in volume down to an accuracy of less than one cubic millimetre found, for instance, that people defined as novelty-seeking personalities had a structurally bigger area of the brain above the eye sockets, known as the inferior part of the frontal lobe.

People with smaller volumes of tissue in this region displayed higher levels of timidity, approval-seeking behaviours and a greater tendency to seek gratification from external sources such as food or drugs, said Professor Annalena Venneri of the University of Hull.

People with "harm-avoidance" personalities had significantly smaller volumes of tissue in brain regions called the orbito-frontal area and the posterior occipital region, compared with other personality types.

"Reward-dependence" personalities stood out for having smaller volumes of tissue in the fronto-striatal and limbic areas of the brain.

If the findings are confirmed by other scientists, they suggest that children are not only born with a given personality type, but they develop anatomically different brains as a result of being that sort of person. It raises the prospect of being able to test a young child's future personality by viewing the anatomy of their brain with a hospital scanner.

"This study shows that personality traits are something you are born with, but their full expression can be modulated during development with the right approach," said Professor Venneri, who carried out the study with colleagues from the University of Parma in Italy and Washington University in St Louis.

The four personality types were classified as "novelty seeking" - characterised by impulsive actions; "harm avoidance" - marked by pessimism and shyness; "reward dependence" - with an addictive personality; and "persistence" - who are people who tend to be industrious, hard-working and perfectionist.

"If you are looking at volume, you are quantifying the tissue that is there. What we found was not just speculative. There is quite a bit of difference between people with different personality traits," said Professor Venneri.

"The fact that traits are reflected in specific anatomical differences is useful to know, for instance when it comes to understanding a child's behaviour and choosing the right approach so that somebody who is, for example, particularly timid might be helped through education and development.

Article continued at:
http://www.nzherald.co.nz/science/news/article.cfm?c_id=82&objectid=10566320

Intelligence is Largely Inherited

Study gives more proof that intelligence is largely inherited
UCLA researchers find that genes determine brain's processing speed
By
Mark Wheeler
3/17/2009

UCLA Newsroom

They say a picture tells a thousand stories, but can it also tell how smart you are? Actually, say UCLA researchers, it can.

In a study published in the Journal of Neuroscience Feb. 18, UCLA neurology professor Paul Thompson and colleagues used a new type of brain-imaging scanner to show that intelligence is strongly influenced by the quality of the brain's axons, or wiring that sends signals throughout the brain. The faster the signaling, the faster the brain processes information. And since the integrity of the brain's wiring is influenced by genes, the genes we inherit play a far greater role in intelligence than was previously thought.

Genes appear to influence intelligence by determining how well nerve axons are encased in myelin — the fatty sheath of "insulation" that coats our axons and allows for fast signaling bursts in our brains. The thicker the myelin, the faster the nerve impulses.

Thompson and his colleagues scanned the brains of 23 sets of identical twins and 23 sets of fraternal twins. Since identical twins share the same genes while fraternal twins share about half their genes, the researchers were able to compare each group to show that myelin integrity was determined genetically in many parts of the brain that are key for intelligence. These include the parietal lobes, which are responsible for spatial reasoning, visual processing and logic, and the corpus callosum, which pulls together information from both sides of the body....

More here: http://newsroom.ucla.edu/portal/ucla/more-proof-that-intelligence-is-85134.aspx

Are You Meant to Be a Bachelor?

Researchers find men with a certain gene are less likely to be married

Men's Health
By: Abby Lerner

If the thought of being in a committed relationship makes you break out into a sweat, there's nothing wrong with you—you may just be programmed to be single.

Swedish researchers looked at variants of a particular gene—the “monogamy gene”—that encodes for a hormone called vasopressin and found that one of these variants (or a lack thereof) is associated with a distinctive kind of pair-bonding behavior in men. The findings suggest an explanation for why some men commit to monogamous relationships while others have a hard time shaking their frat-house habits.

Men who carried only one copy of the “monogamy gene” were more likely to be unmarried or to report some form of marital crisis within the last year, compared to similar men without the gene. Those with two copies of the variant were more than twice as likely to have a dysfunctional marriage, according to the study from the Karolinska Institute in Stockholm.

More than 500 same-sex twin pairs and their spouses or partners of at least 5 years participated in the study and were given tests to determine how bonded they were to each other. Researchers asked questions such as whether the subjects were put off when people came too close, how often the couple did things in common outside the family, and whether either partner had spoken with a close friend about divorce, separation, or marital crisis. Overall, those with the monogamy gene scored lower on the bonding test.

This study adds to previous research done on voles, small rodents often studied for their human-like social qualities, such as picking a mate for life. The researchers cite a vole study which found that the more bonded and social prairie vole has a genetic makeup that differs from their less social and more sexually adventurous cousins, the montane and meadow vole.
So there's scientific data to back it up: Some guys just truly aren't the relationship type....

http://www.menshealth.com/cda/article.do?site=MensHealth&channel=sex.relationships&category=couples&conitem=a23aa41cf6a4c110VgnVCM10000013281eac____

'Warrior gene' predicts aggressive behavior after provocation

January 21st, 2009 in Medicine & Health / Genetics

Individuals with the so-called "warrior gene" display higher levels of aggression in response to provocation, according to new research co-authored by Rose McDermott, professor of political science at Brown University. . . .

Monoamine oxidase A is an enzyme that breaks down important neurotransmitters in the brain, including dopamine, norepinephrine, and serotonin. The enzyme is regulated by monoamine oxidase A gene (MAOA). Humans have various forms of the gene, resulting in different levels of enzymatic activity. People with the low-activity form (MAOA-L) produce less of the enzyme, while the high-activity form (MAOA-H) produces more of the enzyme.

Several studies have found a correlation between the low-activity form of MAOA and aggression in observational and survey-based studies. Only about a third of people in Western populations have the low-activity form of MAOA. By comparison, low-activity MAOA has been reported to be much more frequent (approaching two-thirds of people) in some populations that had a history of warfare. This led to a controversy over MAOA being dubbed the "warrior gene."

Self Control and Belief in God

December 30, 2008
Findings
For Good Self-Control, Try Getting Religious About It
By JOHN TIERNEY

NEW YORK TIMES

...In a new paper [in the upcoming issue of the Psychological Bulletin], Miami psychologists surveyed the literature to test the proposition that religion gives people internal strength.

“We simply asked if there was good evidence that people who are more religious have more self-control,” Dr. McCullough. “For a long time it wasn’t cool for social scientists to study religion, but some researchers were quietly chugging along for decades. When you add it all up, it turns out there are remarkably consistent findings that religiosity correlates with higher self-control.”

As early as the 1920s, researchers found that students who spent more time in Sunday school did better at laboratory tests measuring their self-discipline. Subsequent studies showed that religiously devout children were rated relatively low in impulsiveness by both parents and teachers, and that religiosity repeatedly correlated with higher self-control among adults. Devout people were found to be more likely than others to wear seat belts, go to the dentist and take vitamins.
But which came first, the religious devotion or the self-control? It takes self-discipline to sit through Sunday school or services at a temple or mosque, so people who start out with low self-control are presumably less likely to keep attending. But even after taking that self-selection bias into account, Dr. McCullough said there is still reason to believe that religion has a strong influence.

“Brain-scan studies have shown that when people pray or meditate, there’s a lot of activity in two parts of brain that are important for self-regulation and control of attention and emotion,” he said. “The rituals that religions have been encouraging for thousands of years seem to be a kind of anaerobic workout for self-control.”

In a study published by the University of Maryland in 2003, students who were subliminally exposed to religious words (like God, prayer or bible) were slower to recognize words associated with temptations (like drugs or premarital sex). Conversely, when they were primed with the temptation words, they were quicker to recognize the religious words.

“It looks as if people come to associate religion with tamping down these temptations,” Dr. McCullough said. “When temptations cross their minds in daily life, they quickly use religion to dispel them from their minds.”

In one personality study, strongly religious people were compared with people who subscribed to more general spiritual notions, like the idea that their lives were “directed by a spiritual force greater than any human being” or that they felt “a spiritual connection to other people.” The religious people scored relatively high in conscientiousness and self-control, whereas the spiritual people tended to score relatively low.

“Thinking about the oneness of humanity and the unity of nature doesn’t seem to be related to self-control,” Dr. McCullough said. “The self-control effect seems to come from being engaged in religious institutions and behaviors.”....

Religious people, he said, are self-controlled not simply because they fear God’s wrath, but because they’ve absorbed the ideals of their religion into their own system of values, and have thereby given their personal goals an aura of sacredness. He suggested that nonbelievers try a secular version of that strategy.

“People can have sacred values that aren’t religious values,” he said. “Self-reliance might be a sacred value to you that’s relevant to saving money. Concern for others might be a sacred value that’s relevant to taking time to do volunteer work. You can spend time thinking about what values are sacred to you and making New Year’s resolutions that are consistent with them.”

Of course, it requires some self-control to carry out that exercise — and maybe more effort than it takes to go to church.

“Sacred values come prefabricated for religious believers,” Dr. McCullough said. “The belief that God has preferences for how you behave and the goals you set for yourself has to be the granddaddy of all psychological devices for encouraging people to follow through with their goals.
That may help to explain why belief in God has been so persistent through the ages.”

Why Darwin Would Have Loved Botox

[excerpt]
By Karl Zimmer
Discover Magazine

http://discovermagazine.com/2008/nov/15-why-darwin-would-have-loved-botox/article_view?b_start:int=0&-C=

...When humans mimic others’ faces, in other words, we don’t just go through the motions. We also go through the emotions.

Recently Bernhard Haslinger at the Technical University of Munich realized that he could test the facial feedback theory in a new way. He could temporarily paralyze facial muscles and then scan people’s brains as they tried to make faces. To block facial feedback, Haslinger used Dysport, a Botox-like drug available in Europe.

Botox and Dysport are brand names of a toxin made by the spore-forming bacterium Clostridium botulinum. Botulinum docks on the surface of neurons, blocking the release of a transmitter called acetylcholine. In small amounts botulinum can be fatal. In far, far smaller amounts, it can simply paralyze a small patch of muscles for a few weeks. Haslinger has used Dysport in people with movement disorders like dystonia to help reduce unwanted muscle movement. But Botox and Dysport are best known as treatments to mask aging. Injections into the muscles that make frowns can slow the growth of lines around the eyebrows.

For his brain experiment, Haslinger and his colleagues gave 19 women Dysport injections. Two weeks later the scientists scanned their brains as they showed the women a series of angry or sad faces and asked them either to imitate or just to observe the expressions. Haslinger then ran the same experiment on 19 women without Dysport and compared the two sets of scans.

When the women made sad faces, the same brain regions became active in both those with Dysport and those without. But making angry faces triggered different patterns. In the Dysport-free women, a region known as the amygdala—a key brain region for processing emotions—became active. In the women with Dysport, who could not use their frown muscles, the amygdala was quieter. Haslinger also found another change, in the connections between the amygdala and the brain stem, where signals can trigger many of the feelings that go along with emotions: Dysport made that connection weaker.

Of course neuroscience labs are not the only place where people get shots of Dysport or Botox. According to the American Society of Plastic Surgeons, in the United States doctors administer millions of injections of Botox each year, many of them to people’s faces. Haslinger’s research suggests that this is part of a massive, unplanned experiment.

In June 2008 in the Journal of the American Academy of Dermatology, a team of cosmetic surgeons suggested this experiment is making all of us happier. People with Botox may be less vulnerable to the angry emotions of other people because they themselves can’t make angry or unhappy faces as easily. And because people with Botox can’t spread bad feelings to others via their expressions, people without Botox may be happier too. The surgeons grant that this is just speculation for now. Nevertheless, they declare that “we are left with the tantalizing possibility that cosmetic procedures may have beneficial effects that are more than skin deep.”

Maybe. But for all the Botox youthfulness plastic surgeons may want to think about, neuroscience raises a darker possibility. Making faces helps us understand how other people are feeling. By altering our faces we’re tampering with the ancient lines of communication between face and brain that may change our minds in ways we don’t yet understand.