The Berlin magazine Occulto will soon publish my short story “Remote sensing” – about a young man and his grandfather, a dowser. This is the first time they’ve published a short story. To order a copy of this very interesting magazine, visit:
These remarks were short-listed from the Science Cabaret. Quite a while ago I offered them to the Kansas Board of Tourism to use as an endorsement for our state, free of charge. I am still waiting for a response.
Kansas occupies the exact geographical center of the continental United States. And on the maps they show us in grade school, the US is at the center of the world. This is somewhat inconvenient for the Russians, whose country is split in half – sometimes to go just a little distance from east to west, you have to travel all the way across the world in the opposite direction – but hey, we paid for the map. In cosmological terms, astronomers tell us that if you look up at the stars, all the galaxies in the sky are flying away from us at tremendous speeds. Put all this information together and you discover that Kansas lies at the navel of the universe. At least until a tornado comes, carries us away, and dumps us someplace else.
People are proud of this location but you shouldn’t make a big deal out of it. You have to remember we didn’t choose to live there. A long time ago when the government drew Kansas on a map, that’s where they stuck us. We would have preferred to be closer to one ocean or the other, but nobody asked. Somebody has to live at the center of the universe, and it just happens to be us. Anyway, we have lots of other things to be proud of. Right at the moment I can’t think of any, but ask me again in a couple of weeks. I’ll do some research.
This explains a lot about Kansas. For example, why we get lots of aliens. Imagine you’re zooming across the galaxy, at thousands of times the speed of light, experiencing extensions of time and your bladder. At some point you need a rest stop. We’re conveniently located, we have good coffee, and clean restrooms. And excellent steak, the cheapest in the universe. So aliens drop in all the time. About 25 percent of Kansans claim to have been abducted by aliens. They’re not trying to hurt us. It’s a mistake, they think we’re fast food. If nobody’s at home when they come by, they take one of your cows instead.
Some more little-known facts about Kansas: the state flower is the sunflower, the bird the Meadowlark, and our state song is “Home on the Range.” We learn it in the first grade, and it goes like this:
Oh give me a home where the buffalo roam
And the deer and the antelope play…
When they teach us this song you think, is this really about Kansas? Sure, we have a lot of deer; if you live in the outer suburbs they come right into your yard. Your dogs think they’re toys you’ve brought home, just for their enjoyment. In deer season, people shoot them. But you have to be careful. It’s easy to mistake your neighbors’ lawn ornaments for a deer, and people are quite sensitive about having their lawn ornaments shot to pieces. In deer season it is not unusual to see statues of the Virgin Mary, garden gnomes, and bird feeders dressed in fluorescent orange hunting jackets.
One odd thing about the song is that we know that the plural form of deer is deer. Nobody, even in Kansas, puts an –s on deer. But antelopes… We’re not so sure about that one. “Antelopes” sounds fine to me. So in the song, they’re either talking about one specific deer and one specific antelope, or a bunch of deer and that one particular antelope.
Try as I might, I have never seen that animal. And I’ve looked for it, believe me. Every time I drive through my state, I keep a sharp eye out. But I’ve never seen the antelope. And where are the buffalo that are supposedly roaming around all over the place? Your teacher says, “We killed them all.” Doesn’t seem like nice behavior towards an animal featured prominently in your state song, right there in the first line, but there you have it.
And the song neglects some of the other prominent species in our state. Right now, for example, Kansas is up to its neck in llamas. Everywhere you go these days, somebody’s started a llama farm. I don’t think you can milk one, and their eggs are inedible, but a llama must be good for something. Whatever it is, we should consider changing the state song. For example,
Oh give me a home where the buffalo (used to) roam
And the deer and the camelids play…
The song goes on to say,
…Where seldom is heard
a discouraging word
and the skies are not cloudy all day.
Here, we’re talking outright lies. I’ve heard a lot of discouraging words in my time – most, it is true, from foreigners from places like Paris and New York, but every once in a while a native will rip you with a criticism. And we do have clouds. There is the tall and majestic variety, which look like clipper ships, or six-packs of beer, or Snoopy on his Sopwith Camel, and other times they’re low and grey, hiding tornadoes and hail and all sorts of other unpleasant things.
Or perhaps I’ve misinterpreted this line. Maybe the intent is, “all day long.” To be even clearer, the phrase might mean something like: “All right, we have clouds, but they never stay in the sky all day long, because eventually the wind pushes them into Missouri.” In any case, you have to admit, the original is either a lie or is highly ambiguous.
The state motto is Ad astra per aspera, which is interesting because the number of Latin speakers in Kansas is approximately the same as the number of ancient Romans. If you say it really fast, with a Kansas twang, it sounds like “a disaster for aspirin,” but now we have Google Translate and it’s easily cleared up. Run the motto through the website and you discover it means, “To the stars with difficulty.”
They got that right. It’s difficult for anybody to get to the stars, but it’s a special challenge in Kansas. We don’t have any mountains. If you climb a mountain the stars are still far away, but they’re just a little bit closer. States with mountains have an unfair advantage when it comes to going to the stars.
I have started a new category of post called “Fake papers” which we may use in upcoming scientific writing courses. Students who will be attending a course should check all the articles in this category.
I am writing with regard to the recent publication in your journal concerning the acquisition, maintenance, and loss of a type of speech called a twang. Terris et al. make only cursory mention of – and thus fail to do justice to – a hypothesis that speaking with a twang might be associated with a retrovirus or another pathogen. Our lab has been pursuing this question for over 20 years and I would like to clarify the current status of the debate.
Our search for a pathogen involved in language perception and speech began with a series of observations on the phenotype: in many ways, the spread of the phenotype resembles an epidemic that is tied to particular regions. For example, Valley Fever, or coccidiodomycosis, is caused by a fungus found in dry areas of the Southwestern United States. The fungus forms spores that are spread by winds, particularly when the soil has been disturbed by storms, construction, agriculture, four-wheel drive offroading, motorbiking, or other sports activities. Inhaling the spores leads to an infection in some people.
It is estimated that about a two-thirds of the population of some regions of the Southwest will test positive for the fungus Coccidioides spp. at some point in their lives. Only a fraction develop flu-like symptoms. In severe cases, nodules form on the lungs. Their onset and their severity vary from person to person, likely for genetic reasons, which also play a role in whether the pathogen affects organs beyond the lungs. A weakened immune system greatly increases susceptibility. Symptoms may disappear and reappear over the course of a lifetime.
In many ways the spread of the twang resembles such diseases, which are caused by a pathogen restricted to a particular geophysical niche. There are “hotspots”, particularly in the Midwest, where penetrance reaches nearly 100 percent, surrounded by zones of variable penetrance. Geographical barriers may play a role in limiting its spread. The Rocky Mountains, for example, divide an eastern region of pronounced twang from western areas where it is hardly found at all. There is some evidence that following the Dust Bowl, which saw massive migrations from Oklahoma to California, the pathogen was transported to the western coast, where it was responsible for the rise of “Valley Girl” speech. It has been estimated that in their clothing and shoes, immigrants brought approximately two tons of Oklahoma dust to California. The pathogen may have come along for the ride.
Infants seem particularly susceptible; virtually every child born in a hotspot will acquire the twang, independent of his or her genetic background. Some studies indicate that the degree of penetrance is associated with socioeconomic factors. This, too, is common for pathogens associated with dirt or a lack of sanitary infrastructure. An intriguing observation comes from recent epidemiological work that links the severity of a family’s twang to the number of open beer bottles and pizza boxes lying around the house. Another correlation is the number of rusty cars parked behind the house. In each case, the higher the number, the more severe the twang.
Those exposed during early childhood typically suffer from the twang to some degree their entire lives. Interestingly, those who leave a hotspot for many years – usually decades – may lose many of its features. However, if a person returns home, for example during Thanksgiving, he or she experiences a dramatic but temporary increase in twang speech patterns. This likewise reflects the behavior of some pathogens: removed from their ideal environment, they reproduce only slowly or enter a phase of latency. Contrarily, someone who moves to a hotspot later in life may at some point begin to show symptoms, but only after prolonged exposure.
The hypothetical pathogen does not seem to be transmitted from person to person. Children raised by twang-positive parents in a twang-negative environment do not typically show symptoms. Weaker phenotypes that are occasionally observed might be explained by transmission through contact with fomites such as dust-ridden clothing, furniture, or beer bottles that have accompanied the family without being properly cleaned before a move.
The findings of Terris et al. are intriguing but do not in any way contradict the pathogen hypothesis. A range of infectious agents are known to affect CpG methylation patterns and the expression of genes. Tumors in particular regions of the brain that affect speech patterns may cause symptoms by disturbing neural networks, but they may also be accompanied by changes in the epigenetic regulation of genes.
Validating the twang-pathogen hypothesis will require studies of the metabiome of those affected compared to controls. We have recently carried out such studies using a cohort similar to the patients and controls described in the paper by Terris et al. Our preliminary work, which is currently being revised for publication, has identified three potential candidates: the strongest correlation involves a retrovirus which bears some similarity to the feline leukemia virus, and there is a somewhat weaker association to two species of fungi whose spatial distribution closely matches that of the twang. At the moment we cannot rule out combinatorial effects caused by multiple pathogens, whose lifecycles depend on a delicate balance between body homeostasis and external factors in the environment.
The historical origin of the word “twang” is thought to be an example of onomatopoeia: a word that sounds like what it represents. A twang is the kind of tinny, nasal sound produced by an instrument such as a banjo. It also refers to a type of speech usually associated with the English-speaking population of regions of the Midwestern and Southern United States, as well as several country music singers. The behavior required to produce a twang is complex: speakers apply a nasal quality and usually a rise in pitch to several vowels. Acquiring a twang requires physiological mechanisms ranging from perception (infants hear the speech of those in their environment) to a feedback mechanism (imitation and self-correction) and all the body parts used to produce vowel sounds: the tongue, nasal cavity, mouth, and more extensive pharyngeal structures.
Complex speech phenotypes may have a molecular basis within cells and tissues. Speaking with a twang likely involves several regions of the brain associated with speech and learning as well as those responsible for the coordinated muscular activity of the tongue and soft palette and other parts of the mouth and nasal cavities. Researchers have proposed various mechanisms to account for twang acquisition and performance among speakers. Since the behavior is acquired and can be lost again through training or relocation to an environment where speakers have a different “accent”, it is feasible that epigenetic alterations of genes must be involved. (An early study proposing a retrovirus has been discounted.) There is also some evidence that lesions can be associated with the gain of a temporary or long-term twang, or to the loss of a preexisting twang, which may help in identifying regions of the brain that are involved in its performance.
In a study in the latest issue of Nature Genetics, Terris et al. have studied epigenetic markers around genes that have been implicated in language perception and production in previous studies. They compare the status of these genes in regions of the brain thought to play a part in speech and pronunciation to regions less likely to be involved in these behaviors.
The list of candidate genes was obtained from a database hosted at the Quantitative Neuroscience Lab of Boston University (http://neurospeech.org/–sldb). Additional candidates were obtained through a computational analysis of the PubMed literature, harvesting articles meta-labeled with tags such as the following: twang, speech, language, pronunciation, and nasality.
Tissue samples were obtained from speakers who had undergone brain surgery and were judged to have a pronounced twang (or not) by a mixed audience of native (US-born) linguists. Results were compared between this group and five sets of controls: speakers who had never had a twang, those who had had a twang earlier in life but had lost it, native speakers of French (whose speech is not estimated to have a “twang” but is highly nasal), and a few individuals who had lost or acquired a twang through a stroke or other type of cerebral damage. Evaluations were performed using a standardized “Twang scale” developed at a school of performing arts in Los Angeles. (This program was developed to remove the twang of young actors.) Speakers were graded on a scale of 0 to 10 (0 = British accent; 10 = Bob Dylan).
The lab carried out a comprehensive analysis of methylation patterns across the genome from brain tissue samples from target and control regions for all five groups. The primary method used was bisulfite sequencing, which is based on the treatment of DNA with bisulfite. This causes a chemical conversion of cytosine residues to uracil, but only if the cytosines are non-methylated. Methylated cytosines are protected from the change. Comparing the sequences of treated vs. non-treated DNA permits a base-by-base readout of loci where Cs have been transformed to Us, and those which have not. The results from each group were combined and averaged and filtered for significance. They were compared to each other and to a mixed population of all groups.
The resulting patterns were compared on a chart, which revealed spikes (upward = higher methylation, downward = lower) at specific genomic locations. Both extremes are interesting because the twang phenotype might be due to either higher levels of methylation at particular loci, lower levels, or some combination.
Interestingly, the study revealed a number of significant differences between these patterns in “plus-twang” and “minus-twang” groups. The most extreme variation was found in cells of the superior temporal gyrus and primary auditory cortex, with somewhat smaller (although still significant) peaks in adjacent tissue of the brain region known as Wernicke’s area. The highest difference was found in a region ca. 1 Mb from the FOXP2 gene on chromosome 7, a gene which is highly implicated in many aspects of language acquisition and performance. A bioinformatics analysis of this region revealed a high statistical likelihood that it plays a regulatory role in FOXP2 activation, and contains putative FOX transcription factor binding sites. Both this region and the FOXP2 gene have closely related orthologs whose sequences and relative positions are well conserved between mice and humans. Follow-up studies in mice revealed that deleting the putative regulatory region inhibited expression of the orthologous gene in several areas of the brain, and resulted in a shift in squeaking pitch.
The authors remain cautious about their findings. In the paper’s discussion they report: “The exact molecular mechanisms underlying differential methylation remain to be understood, as does the quantitative significance of the identified loci in twang acquisition (or loss).” To address the mechanistic interplay between methylated regions, their regulators, and the twang-phenotype, the group has developed transgenic Cre mice in which particular methylated regions, methyltransferases, and methyl binding proteins can be deleted in a neuron-specific manner. Additionally, libraries of small molecules are being screened for specific effects on squeaking pitch as a phenotypic marker for twang in the mouse model.
Ideally, a potential twang modulator might be found among approved drugs or natural substances, which can be used to study the methylation status of the FOXP2-associated region. The next step would be to assemble a cohort of patients (twang-plus and twang-minus) who have already tried the drug or substance, checking to see whether this exposure has altered their speech patterns.
The author would like to thank Robert Zinzen for critical review of this article.