Every Friday this month we’ll be taking a look at the relationship between the social and the biological—specifically, how and why the former becomes the latter. Check back next week for a new installment.
To understand how the social becomes biological, scientists often turn to those cases where biology breaks down. Neurologists study patients with brain lesions in order to link specific regions of the brain with speech, behavior, and personality. On a finer level, genetic mutations that lead to inherited disorders expose the wires, gears, and bearings of the molecular machinery beneath human social traits.
One of these molecular gears is histidine decarboxylase, an enzyme that has one job: convert the amino acid histidine into the related chemical histamine. It does this by removing a chemical arm called a carboxyl group—two oxygen atoms, a carbon, and a hydrogen. The resulting histamine has a well-known role in allergies (which is why we take antihistamines like Benadryl and Claritin), but it also functions in the brain as a neurotransmitter (which is why some antihistamines make you drowsy).
Will we ever be able to reason from the behavior of proteins and cells to the behavior of human beings?
Important behavioral traits depend on histidine decarboxylase doing its single chemical job. When it fails, one result is Tourette syndrome, which has been called “the self under siege.” People with Tourette syndrome face almost irresistible urges to make socially inappropriate movements or verbal outbursts. In 2010, a team of Yale researchers found that a broken histidine decarboxylase was the cause of Tourette syndrome in one family, affecting the father and all eight children. The symptoms differed among family members, but included eye rolling, snorting, humming, sighing, grimacing, shoulder shrugging, throat clearing, repeating the words of others, and outbursts of obscenities. The mutation, which the children inherited from their father, is a very small misspelling in the histidine decarboxylase gene, producing a truncated enzyme that can’t remove carboxyl groups to make histamine. In other words, it’s a small chemical change that has enormous behavioral effects.
There is a similar story for FoxP2, a member of a large family of proteins called “forkhead transcription factors.” These are proteins that bind DNA and control when and where certain genes are expressed. All mammals have FoxP2, and unlike many forkhead proteins, FoxP2 has hardly changed during mammalian evolutionary history. But the human version of FoxP2 is unique; it has two changes in its amino acid composition that make it different from the version carried by all other mammals, including chimps. These two small changes to this one regulator protein (changes which Neanderthals shared) are thought to have played a big evolutionary role in the development of language.
Two small changes to FoxP2 helped make human language possible; an equally small change undoes the capacity for language. In a 1990 report, scientists at the Hospital for Sick Children in London described three generations of a family with an inherited speech disorder whose affected members had trouble processing grammar and articulating words. One six-year-old girl was “unable to combine more than two or three words meaningfully.” A 15-year-old boy had “difficulty with word order and with finding words.” The researchers reported that the children “took a long time to name pictures of objects with which they were familiar, and tended to use approximate words” like “sky” for “star.” They had difficulty understanding simple phrases like “the knife is longer than the pencil,” and they “could not retain three items in the correct sequence.” Often, their speech was incomprehensible.
A later genetic study of the family showed that the culprit was a mutation in FoxP2. This small mutation caused an amino acid swap, replacing an arginine with a histidine in a part of the protein called helix 3. This swap alters the function of FoxP2, hampering its ability to bind DNA and control a gene that helps form contact points between neurons in the brain. The ability to use and understand language is severely damaged by this single amino acid switch.
The list of small but crucial defects in molecular parts of behavioral traits goes on: Mutations in the gene SHANK3 break a molecular scaffold and lead to autism. A swap of the amino acid methionine for valine in the enzyme catechol-O-methyltransferase leads to severe anorexia. An isoleucine to valine swap in the serotonin transporter SLC6A4 causes obsessive-compulsive disorder. The mutations that lead to hereditary prosopagnosia, an inability to recognize faces, are currently unknown, but the answer will surely be the same—a small change in a molecular part leads to big social consequences.
I’ve discussed the more obvious cases, the pathological ones where a single mutation has a big, inherited effect. This is when the molecular machinery driving social traits lies exposed and accessible to researchers. When it comes to non-pathological behavior, this machinery is hidden but still there. And its function is affected by the ubiquitous genetic alterations that pervade human biology. For anyone who wants to understand how and why the social becomes biological, there is an obvious challenge here: How do these enzymes, transporters, scaffolds, and transcription factors lead to behavior? Will we ever be able to reason from the behavior of proteins and cells to the behavior of human beings? This can be a dangerous question because it is hard to study and easy to speculate. But it’s a crucial one because we won’t fully understand our most human traits—personality, behavior, language—without making sense of the molecules behind them.
