Flipping the Baby Switch

img_2348-1Rewind to last night. It was bedtime. My infant daughter was screaming and struggling in my lap while I tried to rock her to sleep. She pulled and twisted the skin on my face. She sunk her tiny teeth into my shoulder and chest. Exasperated, I rose from the rocker and started pacing around the nursery. Her tense little body instantly relaxed. Within ten seconds she was quiet and still. Within two minutes she was asleep.

The scene was not unusual for our household. Even as a newborn, my daughter was easy to upset and hard to soothe. When nothing else worked and I was about to lose my mind I’d get up and walk with her. Often the results were nothing short of miraculous. Imagine going from 100 miles per hour to zero in a snap. For those who recall the child android Vicki on the ‘80s TV show Small Wonder, think of the times someone flipped the off-switch on her back. That’s what it’s like when I walk with my daughter. Our aimless walking flips a switch somewhere inside of her. But how does the switch work? And why does she have one in the first place? A study published in Current Biology last month helps to explain this curious facet of infant behavior.

The head scientist behind the study was Dr. Kumi Kuroda at the RIKEN Brain Science Institute in Japan. As she described in an interview with ScienceNOW, she became interested in the topic when she noticed that she could calm her own newborn son by carrying him. She later tested 12 other newborns with their mothers and found that they behaved like her son. Overall, the effect was rapid and dramatic. Some babies stopped crying as soon as their mothers began to walk with them. The rest cried less and were less shrill when they did cry. The babies also moved less and had lower heart rates while they were being carried.

To study the biological mechanisms behind this remarkable calming response, Dr. Kuroda and her colleagues turned to mice. They showed that mouse pups have a similar response when carried by their mothers. Mouse moms carry their pups by the scruff of their necks. When carried, mouse pups less than 20 days old stop wriggling. Their heart rate slows and they stop crying out. (Like most mouse vocalizations, baby mouse cries are ultrasonic). They also draw their legs in when carried, making their bodies more compact for toting around.

Kuroda and colleagues investigated several physiological aspects of the calming response in mice. Only a few of these experiments are probably relevant for infants, since human babies don’t assume a compact position like carried mouse pups do. One looked for the triggers that make carried pups stop squirming. The scientists anesthetized the neck skin of baby mice and found that these animals wriggled more than untreated mouse pups when carried. They got the same result when they overdosed pups with vitamin B6 before testing. (Vitamin B6 overdose causes animals and humans to lose the sense of their body position and movement.) The upshot? For a mouse pup to stop wriggling when carried it must 1) sense that it’s being lifted and 2) sense that something is pulling on its neck skin. Take either sense away and the calming response disappears. My daughter may draw on similar senses to trigger her miraculous stillness while carried. (Only if you replace neck pulling with the pressure of my arms around her, of course. I don’t carry her by her neck skin, I swear.)

The scientists also wondered why a baby’s heart rate drops when it’s picked up and carried. To test this in mice, they gave pups a drug that turns down the parasympathetic nervous system (the set of nerves that return the body to a calm state after arousal). Pups treated with the drug still stopped wriggling when lifted, but their heart rates didn’t drop as they do in untreated pups. So while the parasympathetic nervous system slows down the carried pup’s (and possibly infant’s) heartbeat, it can’t take credit for other features of the calming response.

Clearly this calming response is more complicated than it seems. Many of my daughter’s brain areas, neural pathways, and sensory mechanisms were working in concert to soothe her last night as I walked her in circles. But why does she have this complex reaction to carrying in the first place? Grateful parents might imagine that the calming response evolved to keep us from going crazy, but unless going crazy involves committing infanticide, this explanation doesn’t hold water. Evolution doesn’t care whether parents are happy or well rested or have time to watch Game of Thrones. It only cares whether our offspring survive.

Dr. Kuroda and her colleagues propose that the calming response helped parents escape dangerous situations while protecting their young. According to this logic, calmer carried babies meant faster escapes and higher rates of survival. Certainly if you were running from a wild beast or a member of a rival village, holding a struggling infant might slow you down. Of course holding any infant would slow you down and it’s not clear that sprinting with a struggling newborn is much harder than lugging one that’s asleep.  The paper’s authors present little evidence to support their proposal, particularly in the context of human evolution. They point to a minor result with their mice that doesn’t easily translate to human behavior. In effect, the jury’s still out.

There are other possible explanations for the calming response, ones that don’t involve predators outrunning parents. Shushing can calm crying babies too, probably because it simulates an aspect of their environment in the womb (in this case,  physiological noise). The same could be true of walking with infants. The mothers in the Kuroda study held their babies against their chest and abdomen, which is also how I hold my daughter when I walk to soothe her. The type of movement she feels in that position is probably similar to the rocking and jostling she felt as a fetus in utero whenever I walked. If so, the calming response might be a result of early learning and comfort by association – a nice thought when you consider the gory alternative.

Each year at the end of May we find ourselves as far as possible from Thanksgiving Day. It can be something of a thankfulness drought. This May I am thankful for women in science and maternity leaves, computer-generated dragons and ’80s sitcom androids. And like Vicki’s parents, I am profoundly thankful that my daughter came furnished with an off-switch. Whatever the reason why.

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Photo credit: Sabin Dang

Esposito G, Yoshida S, Ohnishi R, Tsuneoka Y, Rostagno Mdel C, Yokota S, Okabe S, Kamiya K, Hoshino M, Shimizu M, Venuti P, Kikusui T, Kato T, & Kuroda KO (2013). Infant Calming Responses during Maternal Carrying in Humans and Mice. Current biology : CB, 23 (9), 739-45 PMID: 23602481

Remains of the Plague

The history of science is littered with bones. Since antiquity, humans have studied the remains of the dead to understand the living. The practice is as common now as ever; only the methods have changed. In recent years, high-tech analyses of human remains have solved mysteries ranging from our ancestors’ prehistoric mating patterns to the cause of Beethoven’s death. The latest example of this morbid scientific tradition can be found in the e-pages of this month’s PLOS Pathogens. The colorful cast of characters includes European geneticists, a handful of teeth, a 6th century plague, and the US Department of Homeland Security.

Although the word plague is often used as a synonym for disease, plague actually refers to a particular type of illness caused by the bacterium Yersinia pestis. Rampant infection by Y. pestis was responsible for a recent pandemic in the 19th to 20th centuries. Before that it caused the 14th to 17th century pandemic that included the epidemic known as the Black Death.

Yet the pestilence of pestis may have swept across human populations long before the Black Death. According to historical records, a terrible pandemic killed people from Asia to Africa to Europe between the 6th and 8th centuries. It struck the Roman Empire under the watch of Emperor Justinian I, who contracted the disease himself but survived. The pandemic now bears his name: the Justinianic Plague. But was Justinian’s malady really a plague or has history pinned the blame on the wrong bacterium? A group of researchers in Munich decided to find out.

How?

By digging up ancient graves, of course. And helping themselves to some teeth.

The ancient graves were in an Early Medieval cemetery called Aschheim in the German state of Bavaria. The site was a strange choice; the authors reveal in their paper that the historical record shows no evidence that the Justinianic Plague reached Bavaria. However, the site was conveniently located within driving distance of most of the study’s authors. (It’s always easiest to do your gravedigging closer to home.) The authors did have solid evidence that the graves were from the 6th century and that each grave contained two or more bodies (a common burial practice during deadly epidemics). In total, the group dug up 12 graves and collected teeth from 19 bodies.

The scientists took the teeth back to their labs and tested them for a stretch of DNA unique to Y. pestis. Their logic: if the individuals died from infection by Y. pestis, their remains should contain ample DNA from the bacteria. Of course, some of this DNA would have deteriorated over the course of 1.5 millennia. The scientists would have to make do with what they found. They used three different methods to amplify and detect the bacterial DNA, however they only found a reliably large amount of it in the teeth of one individual, a body they affectionately nicknamed A120. They genotyped the Y. pestis DNA found in A120 to see how the bacterial strain compared with other versions of the bacterium (including those that caused the Black Death and the 19th-20th century plague pandemic.) The analysis showed that the Justinianic strain was an evolutionary precursor to the strain that caused the Black Death. Like the strains that sparked the second and third pandemics, this strain bore the genetic hallmarks of Y. pestis from Asia, suggesting that all three plague pandemics spread from the East.

The authors write that they have solved their historical mystery.

“These findings confirm that Y. pestis was the causative agent of the Justinianic Plague and should end the controversy over the etiological agent of the first plague pandemic.”

Ordinarily, the discussion sections of scientific papers are littered with qualifiers and terms like might be and suggestive. Not so here, even though the authors’ conclusion explains a phenomenon that killed many millions of people worldwide based on data from the decomposing remains of a single person who lived in a region that historians haven’t connected with the pandemic. In most branches of science, sweeping conclusions can only be made based on large and meticulously selected samples. In genetics, such rules can be swept aside. It is its own kind of magic. If you know how to read the code of life, you can peer into the distant past and divine real answers based on a handful of ancient teeth.

As it turns out, the study’s result is more than a cool addition to our knowledge of the Early Middle Ages. Plague would make a terrible weapon in the hands of a modern bioterrorist. That’s why the US Department of Homeland Security is listed as one of the funding sources for this study. So the next time you hear about your tax dollars hard at work, think of Bavarian graves, ancient teeth, and poor old A120.

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Photo credit: Dallas Krentzel

ResearchBlogging.org

Harbeck M, Seifert L, Hansch S, Wagner DM, Birdsell D, Parise KL, Wiechmann I, Grupe G, Thomas A, Keim P, Zoller L, Bramanti B, Riehm JM, Scholz HC (2013). Yersinia Pestis DNA from Skeletal Remains from the 6th Century Reveals Insights Into Justiniac Plague PLOS Pathogens DOI: 10.1371/journal.ppat.1003349