Field of Science


Marsupials Make the Best Medicine

We're waging an increasingly desperate war on drug-resistant bacteria. Thanks to their adaptability--and our own fondness for strewing antibiotics everywhere, like inept military commanders who let the enemy borrow and examine our only weapons before we attack--the bugs are gaining ground. Previously life-saving drugs are now useless, and previously beatable infections now have strains that seem immortal.

To find new antibiotics that can help us, why not turn to animals that are still doing a good job keeping harmful bacteria at bay? In a recent study published in PLoS ONE, Australian researchers turned to two such animals. The first was the tammar wallaby.

A kangaroo relative, the wallaby gives birth to bean-sized young that live in a pouch until able to survive on their own. (You can see a joey's face sticking out in the picture above.) The other animal chosen for study was the platypus, a mammal that's famous for laying eggs and looking like someone's idea of a joke.

The researchers picked these animals for a few reasons. Most practically, their genomes had recently been sequenced. They're biologically interesting because they represent our most distant mammal relatives: Their two lineages, the marsupials and the monotremes, diverged before the rest of us mammals had settled on placentas and live birth as the best way to make babies. The wallaby delivers its young after just 26 days in the womb, after which the baby stays in the pouch for 9 or 10 months, drinking milk from its mother's teat. Young platypuses hatch from their eggs in a similarly underdeveloped state, then stay in a burrow for a few months while they drink milk that leaks straight out of their mothers' skin.

What's most relevant about the platypus and wallaby is that their young, coming into the world at such a vulnerable stage, must be extremely well protected from infection--whether that protection comes from agents in their own bodies, their pouches, or their mothers' milk. The researchers combed through the two animals' genomes to look for antimicrobial proteins called cathelicidins. Humans make just one kind of cathelicidin, but these proteins have been found in a wide range of animals and can destroy bacteria, fungi and protozoa.

In keeping with the hypothesis that marsupials and monotremes need to have a lot of protections in place for developing young, the researchers found eight cathelicidin genes in the platypus and 14 in the tammar wallaby. In the tammar, these genes were active in the mammary glands during lactation, and in the skin of young living in the pouch.

But why sit around and speculate about how effective these antimicrobial proteins are? The researchers picked two cathelicidin genes from the wallaby and two from the platypus, then manufactured some of the actual proteins they coded for. Then they tested these proteins against a host of bacteria.

If bacteria had blood, it would have been a bloodbath. The wallaby and platypus proteins killed B. subtilus, staph (S. aureus), two kinds of strep (S. uberis and S. pyogenes), E. coli, Salmonella choleraesuisPseudomonas aeruginosa, and the fungus C. albicans, which causes yeast infections. The four proteins were all more powerful than the human cathelicidin.

One wallaby protein, in particular, was up to 80 times more effective than its human version against the various microbes. Against E. coli and B. subtilis, it was 10 times more effective than commercial antibiotics such as ampicillin or tetracycline. When the researchers put this wallaby protein back in the ring with multidrug-resistant bacteria, it killed A. baumanniiK. pneumoniae, and a bacterium called P. aeruginosa that can resist even last-ditch antibiotics.

Our ancient mammal ancestors may have naturally produced a greater number of antibiotics, like the tammar wallaby and platypus do, to protect themselves and their vulnerable young from infections. Over time, the placental mammals seem to have lost those genes, giving up antimicrobial abilities while keeping our young protected in our bodies for longer. But with the threat of drug-resistant bacteria, we've become vulnerable again. To develop new lifesaving drugs, we may have to enlist the help of distant relatives that followed a different evolutionary path.

Photos: tammar wallaby and joey Wikimedia/Mathae; platypus

Wang, J., Wong, E., Whitley, J., Li, J., Stringer, J., Short, K., Renfree, M., Belov, K., & Cocks, B. (2011). Ancient Antimicrobial Peptides Kill Antibiotic-Resistant Pathogens: Australian Mammals Provide New Options PLoS ONE, 6 (8) DOI: 10.1371/journal.pone.0024030

Can the Flu Make You Narcoleptic?

Narcolepsy doesn't strike at random. After studying the medical records of a large group of Chinese narcoleptics, researchers concluded that their symptoms--sudden naps, constant sleepiness, hallucinations--were most likely to have started in the month of April. In fact, each year's new cases of narcolepsy appeared in a cyclical pattern, following the seasons. Could narcolepsy be a delayed reaction to the flu?

The brains of narcoleptics fail to produce enough hypocretin (also called orexin), a hormone that regulates wakefulness. It's a disorder that most often begins in childhood, and sometimes runs in families. In popular culture, narcolepsy sufferers have a tendency to fall asleep at comically inconvenient moments. But this view ignores narcolepsy's most ridiculous symptom, called cataplexy. Not all narcoleptics experience cataplexy, but those who do may lose all strength in their muscles during moments of strong emotion. A fit of anger or laughter can leave a person paralyzed on the floor for several minutes.

Though it's not known what causes the onset of narcolepsy, one theory is that it's an autoimmune disorder: The immune system, overreacting to some trigger, attacks hypocretin-producing neurons in the brain. (Similarly, multiple sclerosis is an autoimmune disease that damages neurons throughout the body.) In the event of an immune system uprising, certain people's genetics might guide the attack to the brain's hypocretin neurons. Eventually, enough neurons are damaged or lost that narcoleptic symptoms set in.

After the H1N1 pandemic, there were suggestions that flu vaccinations might have triggered new cases of narcolepsy. To examine this claim, researchers from Beijing University People's Hospital and Stanford University examined the medical records of 906 narcoleptic patients who had been diagnosed in Beijing between 1998 and 2010. For 629 of the patients, researchers knew the month and year in which symptoms began. (These dates were reported after the fact, which could introduce error. But since most of the patients were young children when their symptoms began, the months and years in their records would have come from their parents, whom you'd expect to have a pretty accurate idea of when their child began falling asleep spontaneously in the middle of the day.)

The researchers found that new narcolepsy cases followed a yearly cycle that peaked in April. The fewest new cases occurred in November. And it wasn't a small difference between the top and bottom of the cycle--nearly seven times as many new cases occurred in April as in November. They also saw a huge leap in narcolepsy cases in 2010, with three to four times as many new patients as normal.

Comparing these trends to government data, the authors found that the narcolepsy cycle lagged about six months behind the seasonal cycle of influenza and colds. The spike in 2010 had come six months after the height of the H1N1 pandemic in China.

There was no connection between new narcolepsy cases and flu vaccines, though. Researchers surveyed patients who had developed narcolepsy after the H1N1 pandemic, and found that only 5% had received a vaccine.

Although the researchers couldn't test it directly, the results fit with the theory that infection by influenza can trigger narcolepsy in vulnerable individuals. The infection may set off an autoimmune reaction that, around six months later, has destroyed enough hypocretin neurons to bring on serious symptoms. Though the correlation between the flu cycle and narcolepsy cases could be circumstantial, the spike after the H1N1 pandemic adds some weight to the idea. Previous studies found a possible connection between narcolepsy and strep throat infections. The authors mention, too, that after the 1918 flu pandemic, there was an increase in cases of a brain-lesion disorder.

Even if the infection theory is true, some questions remain. Is narcolepsy inevitable in individuals who develop it? When the disorder sets in during childhood, does it mean the brain was doomed from the start, and the child was one serious infection (or other trigger) away from becoming sick? Or can some narcolepsy cases be avoided? The Chinese data appear to show a slow but steady rise in new cases between 1998 and 2010, which might suggest that environmental factors are outweighing genetic ones. If the disorder is avoidable, further research may show us how to prevent narcolepsy, so that during the flu epidemics of the future we can protect our brains as well as our bodies.

Han, F., Lin, L., Warby, S., Faraco, J., Li, J., Dong, S., An, P., Zhao, L., Wang, L., Li, Q., Yan, H., Gao, Z., Yuan, Y., Strohl, K., & Mignot, E. (2011). Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in china Annals of Neurology DOI: 10.1002/ana.22587 This post was chosen as an Editor's Selection for

Science's Biggest Cancer Questions

The National Cancer Institute wants to give out $17.5 million to scientists studying the biggest unanswered questions about cancer. To figure out what those unsolved mysteries are, NCI director Harold Varmus pooled ideas from researchers, eventually developing a master list of 24 "provocative questions." The NCI is now inviting researchers to apply for some of that grant money--but scientists are only eligible for part of the pot if they promise to specifically address one of the 24 questions.

Some of these unanswered questions (or PQs, as the Cancer Institute has catchily dubbed them) are old, neglected mysteries. Others are based on newer observations. And some are questions that we haven't had the technology to address in the past, but that seem more attainable today.

Eight of the most provocative questions are below, rephrased by me but numbered so you can find their original language if you'd like. All 24 original questions are here. (The NCI wants to be clear that their numbering system is strictly random, presumably so they don't receive eight thousand grant proposals for PQ 1.)

Why are patients with diseases such as Alzheimer's, Parkinson's or Huntington's significantly less likely to get cancer? (PQ 6)
The reverse is also true: People who have survived cancer have a lower risk of developing these neurological disorders. It's unusual to study anti-correlations rather than correlations--usually we want to know what makes us more likely to be sick. But teasing out the molecular and cellular mechanisms that prevent cancer patients from developing Alzheimer's, and vice versa, would teach us a lot about cancer--and about these other illnesses.

How are obesity and cancer connected? (PQ 1)
Obese individuals have a greater risk of many types of cancer. But scientists don't know what, specifically, connects cancer and obesity. It's also unclear whether losing weight lowers a person's risk of cancer. Once someone becomes obese, has the carcinogenic switch already been flipped? Are some risks reversible?

What does an animal's lifespan have to do with cancer? (PQ 7)
In humans, most cancers are diseases of aging. Young people with cancer are a relative rarity; as we use up more of our 80 or so years, our cancer risk rises. In animals that are susceptible to cancer, their disease looks similar to ours. But their lifespans can be radically different. Mice only live about 2 years, yet we can easily model cancers in them. Dogs can develop cancer within their 15 or 20 years of life.

Not all animals have a cancer problem, though. Sea turtles can live for at least as long as humans, if not decades longer, and seem to almost never get cancer. We clearly have a lot to learn about how animals, including humans, age. We also have yet to elucidate the ways in which cancer is, and is not, a disease of aging.

How many cancers are caused by viruses? (PQ 12)
The discovery that viruses caused most cervical cancers led to the development of an HPV vaccine. Some other cancers are known to be linked to viral or bacterial infections. By finding out which types of cancers come from catchable agents, we can learn more about how tumors form and might even be able to create new cancer vaccines.

Why do some types of cancer cluster in geographic regions? (PQ 2)
Your risk for some cancers varies depending on where you live--and if you move, your risk will change. Which of these cancers are being caused by a toxin or other environmental factor? Which are caused by cultural factors such as diet?

Can we find extra-tiny tumors? (PQ 13)
Current imaging technology already has a pretty impressive resolution; doctors can spot tumors that are just one cubic millimeter in size. But could improved technologies reveal tumors that were orders of magnitude smaller? What about a single tumorous cell?

Why do cancer survivors have a higher risk of developing a second cancer? (PQ 15)
Some of a former cancer patient's risk might have to do with the chemotherapy and radiation she or he has already undergone. But if there's more to the story, it might reveal underlying factors that put a person at risk for all cancers--not just cancer of the stomach or skin or prostate.

Could we quantify a person's cancer risk? (PQ 3)
Perhaps in the future, a tool or test in the doctor's office could analyze a blood sample and report back on your current risk of developing cancer, based on carcinogens or metabolic products in your body. Or we could keep sensors in our homes--or wear them on our bodies--that measure our cumulative exposure to carcinogens. What if everyone wore a cancer watch that counted down their healthy days? (You're free to use that idea for a dystopian science-fiction novel. But please send me a copy.)

Climate Change Creates Ambidextrous Animals

Even animals without hands can display handedness--or, at least, a preference to do things with one side of the body rather than the other. Animals ranging from primates to birds to invertebrates have been shown to favor their left or right side. Fish might reveal that preference by choosing to swim right, for example, when avoiding a predator. Don't get too charmed by the idea of left-handed and right-handed fish, though: In a warming world, they may disappear.

A new study by researchers in Italy and Australia looked at young coral reef fish, Neopomacentrus azysron, which often display a preference for the right or left side. (Humans are unusual in that almost all of us prefer the right side. In other animals, individuals might be biased toward one side or the other, but the population as a whole tends to be evenly distributed.) To measure the reef fishes' preference, the researchers put them in a very elementary maze: It was shaped like a T, and fish had to swim either right or left at the end.

As some hard-working fish wranglers put 70 baby reef fish through the maze 10 times each, the researchers recorded the preference of each individual fish to turn right or left. They also performed a random simulation of fish going through the maze, to see what the results would have been like if fish were choosing their direction arbitrarily. There was a significant difference between real fish and simulated fish: This meant the baby reef fish were displaying a true preference for the right or left side, or "lateralization."

Another group of baby reef fish were kept for four days in water with an elevated level of carbon dioxide. As CO2 in the atmosphere increases, causing global warming, more of it is also absorbed by the oceans. The carbon dioxide level in the water that housed these baby fish, the authors say, is a level our oceans are predicted to reach between the years 2050 and 2100.

After being kept in the high-CO2 water, these reef fish also took their turn in the T-shaped maze. Unlike the fish raised in normal water, though, high-CO2 fish showed no preference for turning right or left. Their results were indistinguishable from the random simulation.

The increased CO2 seems to have affected the neural development of these animals. But what does it matter if climate change wipes out right- or left-handed fish? Preferring one side over the other, in fish or in humans, isn't just a biological fluke. The authors say reef fish may choose the right or left side because one of their eyes is stronger than the other. Having a bias toward one side allows fish to make a quick decision when avoiding a predator: In a previous study, fish from areas with high predation were found to have stronger lateralization, suggesting that preferring one side or the other is an evolutionary advantage.

It's not just about turning left or right. Lateralization in animals' behaviors reflects the underlying asymmetry in our brains. It's thought that dividing tasks between the two sides of the brain makes us more efficient, like a computer using parallel processing. Fish with a right or left preference have been found to perform better in various cognitive and physical challenges.

In a warming world--and an acidifying ocean--will ecosystems fall apart as fish and other animals lose the skills evolution has selected? A study published last year found that clownfish raised in elevated CO2 levels chose to swim toward the smell of a predator, rather than away. Their sense of smell seems to have been damaged by living in acidified water. Or maybe they were suicidal because they couldn't decide which fin they preferred to write with. Either way, the future is looking stormy for ocean ecosystems.

Domenici, P., Allan, B., McCormick, M., & Munday, P. (2011). Elevated carbon dioxide affects behavioural lateralization in a coral reef fish Biology Letters DOI: 10.1098/rsbl.2011.0591

Boyz Turning 2 Men Sooner than Ever

Despite how it may have seemed when you came back from summer vacation to start eighth grade and every boy's voice had changed at once, the age of human adolescence isn't set in stone. A German demographic researcher says that the age of sexual maturity in males has been steadily decreasing since the mid-eighteenth century. And he reached this conclusion based on the rate at which young men get themselves killed.

Human males have an unfortunate tendency to die in early adulthood. Recklessness and violence aren't just traits of young males in the modern era. Even in earlier centuries, when young men had to satisfy their adrenaline cravings with buggy racing, dueling, or hanging around smallpox patients, they were more likely to die than women of the same age.

This leads to a phenomenon called the "accident hump." Both sexes have a relatively high risk of dying as an infant, but that risk plummets throughout childhood. Mortality bottoms out in older kids, when the threat of childhood disease recedes and adult ailments are still far in the future. As adolescent girls move into adulthood, their risk of death slowly and steadily climbs. Each adult year that you're alive has a greater chance of being your last. But for males, the mortality rate takes a sudden leap above females in early adulthood. This is the accident hump. As men get a little older and leave behind their risky or violent behaviors, their risk of death smooths out again to match the steady climb of female mortality.

Joshua Goldstein, at the Max Planck Institute for Demographic Research, says that the accident hump has been shown to coincide with sexual maturity, the time when male bodies are cranking out their highest levels of testosterone. Other studies have shown that female sexual maturity, measured by the age when menstruation starts, has come earlier and earlier over the past few centuries. As humans have developed better medicine and nutrition, our bodies have been able to grow bigger and mature sooner. Has sexual maturity also been arriving earlier for males?

To find out, Goldstein looked at death data from several European countries with thorough records. The dataset began in the mid-1700s. In each decade, he determined the age at which the accident hump peaked; this would roughly represent the average age of male sexual maturity.

He found that throughout the nineteenth and twentieth centuries, the accident hump came about 0.2 years earlier in each decade. In the late 1800s, young European men were dying most often around age 21. In 2000, that age was closer to 18.

So at the same time that humans were getting bigger and healthier, the peak of males' dangerous behavior was getting earlier. Has the onset of male adolescence also grown earlier? Goldstein says there's other evidence beside mortality rates. A study of boys' choirs found that in a choir lead by J. S. Bach in mid-eighteenth-century Germany, boys' voices didn't change until they were 18 years old, on average. But in twentieth-century London choirs, boys' voices changed much earlier, around age 13.

Earlier sexual maturity might mean teenagers are driven to try risky behaviors (and girls are able to get pregnant) at increasingly younger ages. Goldstein wonders how brain development, which continues into early adulthood, compares to sexual development. If the timing of brain maturation has stayed the same while physical maturation has grown earlier, does this make for an increasing gap between physical and mental adulthood? Goldstein also points out that in the past half-century or so, cultures around the world have seen the milestones of adulthood--marriage, financial independence, parenthood--pushed to later in life. Essentially, though most of us would have cringed to hear it in seventh grade, we may all be living out a longer adolescence.

Goldstein, J. (2011). A Secular Trend toward Earlier Male Sexual Maturity: Evidence from Shifting Ages of Male Young Adult Mortality PLoS ONE, 6 (8) DOI: 10.1371/journal.pone.0014826

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Nesting-Doll Bugs Make a Complete Set

Describing what might make the worst gift ever, researchers John McCutcheon and Carol von Dohlen report that they've found a system of symbionts resembling Russian nesting dolls. A tiny bacterium lives inside a slightly less tiny bacterium, which lives inside a mealybug. Unlike a nicely painted set of wooden dolls, though, each complete on its own, the matryoshka mealybug and its many inhabitants can't live without each other.

The citrus mealybug, Planococcus citri, is a a sap-sucking plant pest barely an eighth of an inch long. It's notable for destroying fruit crops and for being herded by ants, which fend off the mealybug's predators in exchange for eating its secretions.

As if being farmed by ants weren't insult enough, P. citri needs bacteria to live inside it and provide it with essential nutrients. Other symbiotic relationships have been observed between insects and bacteria, with insects sometimes harboring multiple bacterial species that help them maintain a balanced diet. But the citrus bug has a never-before-seen system: Inside its symbiont called Tremblaya lives an even smaller bacterium the authors call Moranella.

The medium-sized bacteria are, like the mealybug, a little pathetic. The authors call Tremblaya's genome "extremely small and degenerate." In fact, it's the smallest genome ever reported, with a meager 139,000 base pairs. (For reference, the human genome has 3 billion base pairs, which is medium-large among living things.)

Because Tremblaya has such a reduced genome, it's missing the equipment to make many nutrients for itself. So it, in turn, relies on the tiny Moranella bacteria that live inside it. But even Moranella is lacking some genetic tools. All three organisms, it seems, must rely on each other to help manufacture their essential amino acids.

It's still mysterious just how the three organisms complete the complex molecular pathways required to make these nutrients. At various steps in these pathways, the symbionts would have to pass molecules between each other; the authors say it's "unclear" how this works. They speculate, though, that the Tremblaya bacteria may simply crack open the Moranella bacteria living inside them to get the molecules they need.

Tremblaya bacteria may be rude hosts, but the mealybugs seem to be more delicate, somehow regulating the numbers of both bacteria inside them. Like the mind-controlling fungi that prey on insects, or the whole ecosystems of bacteria and viruses that live inside humans, mealybugs prove that even the most unimpressive organism can show us something new.

Photo: Planococcus citri, by J. Davidson/USDA

McCutcheon, J., & von Dohlen, C. (2011). An Interdependent Metabolic Patchwork in the Nested Symbiosis of Mealybugs Current Biology DOI: 10.1016/j.cub.2011.06.051

The Sniff Test for Mental Illness

Imagine a patient goes to see his general practitioner, complaining of exhaustion. He can't sleep, and he'd like a referral to a sleep clinic so he can get some answers. First, his doctor wants to administer a quick test. She holds a device like a felt-tipped pen just under her patient's nose and has him sniff. "Sure, I can smell that," he says. She gives him three pens and asks which one smells different from the other two. "They all smell like peppermint to me," the patient says. "Okay," the doctor says, "I'm referring you to a psychiatrist."

This type of test, if it exists someday, would take advantage of the fact that your brain's components aren't just responsible for one job apiece. For example, an area right above your eyeballs called the orbitofrontal cortex is involved in decision making and emotions--and your sense of smell. According to researchers in Belgium, a test of olfactory abilities might be able to alert doctors to an underlying condition such as depression, dementia, or schizophrenia.

Pierre Maurage and his colleagues studied a group of 20 alcoholics who were receiving treatment and hadn't drunk for at least two weeks. Each alcoholic was matched with a control: a person of the same age, sex, and education level who had no history of psychiatric problems or substance abuse.

Subjects took three kinds of tests. The first set of tests measured their olfactory abilities. Subjects were given pens to sniff; researchers assessed their sensitivity to different concentrations of odors, their ability to tell different odors apart, and whether they could correctly identify what they smelled.

Next, subjects took two cognitive tests. In one test, they looked at words on a screen and had to press a button to indicate whether each word was an animal or an object--but if they heard a beep, they had to stop themselves from answering the question. This is a test of general cognitive functioning that doesn't specifically involve the orbitofrontal cortex.

The third test was one that is known to activate the orbitofrontal cortex. Subjects had to view a series of pictures and say whether they'd seen them already or not. Later in the day, they repeated the test, and were asked to forget what they'd seen in the first test. If subjects had trouble remembering whether a picture was familiar because they'd seen it a few moments ago or earlier in the day, they were given a high "confabulation" score. Confabulation is the tendency to fill gaps in your memory with false events; it's a problem some alcoholics have.

Both groups of subjects, the alcoholics and the controls, scored the same in the general cognitive test. But in the confabulation test, alcoholics performed worse. They also did worse in the sniffing tests. Alcoholics didn't have an impaired sense of smell overall; they could detect scents at the same threshold as non-alcoholics. But they had a harder time identifying odors and telling two odors apart. This indicates that the problem isn't in the actual smelling, but in the brain's processing of smells.

So although the researchers weren't able to confirm their observations with brain scans, it seems that alcoholics had impaired brain functioning specifically in the orbitofrontal cortex. In addition to causing confabulation, this affected their performance on a smell test.

If this relationship proves to be reliable, it could give doctors a shortcut to test their patients' mental functioning. A sniff test given to alcoholics could reveal how likely they are to be experiencing memory gaps. Smell tests given to patients with other psychiatric disorders that affect olfaction (such as depression, dementia, anorexia, or schizophrenia) could provide clues as to what cognitive problems they're having--or whether certain brain areas are working just fine. And in other patients, a poor smelling score could suggest an undiagnosed mental illness. Since this study found a result in odor processing in the brain, though, and not subjects' ability to detect odors generally, you don't have to worry that a head cold will get you sent to therapy.

For now, doctors will have to rely on probing questions and physical exams rather than scented pens. And no one knows what was going on with that kid in your kindergarten class who couldn't stop sniffing the grape Mr. Sketch marker--though if smell tests are introduced in doctor's offices, one assumes he'll be thrilled.

Maurage, P., Callot, C., Chang, B., Philippot, P., Rombaux, P., & de Timary, P. (2011). Olfactory Impairment Is Correlated with Confabulation in Alcoholism: Towards a Multimodal Testing of Orbitofrontal Cortex PLoS ONE, 6 (8) DOI: 10.1371/journal.pone.0023190

The Hidden Advantage of Twins

For humans and other animals that traditionally have just one baby at a time, twins are a gamble. Pregnancy is riskier for the mother and the fetuses. If the twins make it to birth, they're likely to be undersized. And even if she has two healthy babies, a mother must find twice as much food as usual to keep them that way--and must keep twice as many helpless, chubby morsels away from the lions. But if both kids survive to adulthood, the parents will have doubled their genetic contribution to the next generation.

Presumably because it's an evolutionary trade-off with so many variables, the rate of twinning has evolved differently across human populations. This variation applies only to "dizygotic," or fraternal, twins. Identical (or "monozygotic") twins are more rare, and their frequency of about 0.4% stays fairly constant across populations. One embryo splitting into two seems to be a random accident. Dizygotic twinning, though, seem to result from genetic tendencies; some mothers are more likely to release two eggs simultaneously.

One potential explanation involves hormones called insulin-like growth factors (IGFs). The IGF system may affect a mother's chances of releasing multiple eggs. It's been linked to twinning in a study of cattle (another mammal that usually sticks to one calf at a time). IGF hormones have also been linked to the growth of a fetus. This led a group of researchers in the UK to ask whether mothers who give birth to twins, thanks to the effect of IGF hormones, also give birth to larger non-twin babies.

The researchers, led by Ian Rickard, used data collected from Gambian women between 1978 and 2009. These women had an average of about 7 children each. Researchers divided the women into those who gave birth to twins at some point, and those who never had twins. They found that "singleton" (non-twin) babies born to twinning mothers were significantly larger, on average, than babies born to non-twinning mothers. In other words, twinning mothers--when they're not having twins, which are usually small--give birth to heavier babies. This effect was independent of the mothers' BMI or height. It even held true for singleton babies that were born before their twin siblings: these babies were heavier at birth than singleton babies born to mothers who never had twins.

The only time the effect didn't appear was when mothers were exposed to the "hungry season," the furthest time from the harvest, during their third trimester. With more limited resources during their pregnancies, twinning mothers gave birth to babies that were roughly as small as non-twinning mothers' babies.

Though the dataset doesn't include information on IGFs or other hormones, it seems that some underlying factor causes mothers both to have twins (because they release two eggs at once) and to have large singleton babies. The researchers also don't know how many of these sets of twins were actually identical, or monozygotic (the less-common variety). But since monozygotic twinning seems to happen randomly, mothers of identical twins would presumably dilute the effect seen here. So if anything, the birthweight advantage in twinning mothers might be even greater than it seems.

Whatever is underlying it, the study shows that there's an advantage to twinning--or, at least, that twinning is a side effect of an advantageous trait that makes for sturdier singleton babies. This might help to explain why twinning has evolved to be more common in some human populations than in others. Each population has its own pressures, and must strike its own balance between factors such as birthweight and survivorship. Thanks to the intricate mathematics of natural selection, twins are never just a twofer.

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Rickard, I., Prentice, A., Fulford, A., & Lummaa, V. (2011). Twinning propensity and offspring in utero growth covary in rural African women Biology Letters DOI: 10.1098/rsbl.2011.0598

Sneaky Squid Use Custom-Sized Sperm

How big should your sperm be? If you're a squid, it depends where you're putting them.

Males of the species Loligo bleekeri follow one of two mating strategies. Larger males mate with a female in the traditional way (for a squid), depositing packets of their sperm inside her oviduct. They then guard the female to make sure no other males mate with her. Small males, on the other hand, don't bother with the colorful displays that are required to woo and mate with a female. Instead, they dart up to an established squid couple and stick some sperm packets on the female's head.

This may seem futile, but the females of L. bleekeri happen to have a secondary sperm-storage organ near the mouth. The so-called "sneaker" males aim for this receptacle when adding their contribution to the mix. When a female eventually extrudes a string of eggs, it passes by both the internal and external sperm stores before landing on the sea bed. This gives all males involved a chance to father some bouncing baby squid.

A group of researchers in Japan and the United Kingdom, led by Yoko Iwata, collected female and male L. bleekeri squid, including both large and small males. They relieved the males of their sperm packets, called spermatophores, and studied their contents. What they saw was that squid sperm come in two distinct sizes. Large squid have smaller sperm, and small squid have larger sperm. (Before you ask, both varieties are larger than human sperm.) And the two sperm sizes are completely segregated between the two receptacles in a female.

It's the first time a single species has ever been discovered to have two separate sperm types. The squid themselves come in two distinct sizes, too; they seem to be built specifically for one mating strategy or the other. How they develop this way is unknown.

The different sizes of sperm don't seem calibrated for competition with each other, though. In swimming tests, large and small sperm were equally fast. They also were both able to fertilize eggs. The researchers speculate that the different sperm sizes have evolved due to the environments they're left in. Small squid leave their sperm out in the open, where they're more susceptible to being washed away by water. Other factors that differ between the two fertilization environments, "such as salinity, viscosity, pH and concentrations of gases and nutrients," may have influenced the evolution of large and small sperm. Each size of sperm seems to be optimized for the mating strategy it's used in, giving both sizes of squid a fighting chance at fertilization.

Squid are far from the only animals to employ spermatic gamesmanship. Unromantic males of various other species use a "sneaker" strategy. For example, in the European common frog Rana temporaria, a  "pirate" male searches for freshly laid piles of eggs, then deposits his sperm directly onto them. The eggs have already been fertilized once before, as the female released them, by the male who was actually mating with her. But the pirate has a chance to fertilize any eggs in the batch that got missed the first time. To increase his odds, he sometimes crawls bodily into the egg mass before doing the deed.

Other species use a "copulatory plug," a sticky mass left in the female after mating to prevent other males' sperm from getting in. This is a popular strategy that shows up in species ranging from bumblebees to snakes to squirrels to monkeys. Males of the orb-weaver spider Nephila komaci, not messing around, break off their genitalia in the female to serve as a plug. The male black-winged damselfly has a penis shaped like a scrub brush, which he uses to scrub away his rivals' sperm. In an especially creative adaptation, some rodents produce hooked sperm that join together in transit to form (this is an actual scientific term) sperm trains.

Sperm competition is a high-stakes game; it's the difference between passing on your genes and not. Females, whose only directive is to find the fittest male to fertilize her eggs (if she gets any choice in the matter), don't face nearly the same evolutionary arms race. I'm sure that's some consolation to the female L. bleekeri, drifting through the ocean with sperm packets glued all over her head.

Iwata, Y., Shaw, P., Fujiwara, E., Shiba, K., Kakiuchi, Y., & Hirohashi, N. (2011). Why small males have big sperm: dimorphic squid sperm linked to alternative mating behaviours BMC Evolutionary Biology, 11 (1) DOI: 10.1186/1471-2148-11-236

Yeast Show Humans Why It's Better to Be a Clump

When the first single-celled organisms left behind their loner ways and began existing as blobs of cells, it was a big step for life on this planet. Organisms could now grow orders of magnitude larger than each other. They could organize their cells into different types that performed different functions. Instead of drifting around with the other specks, multicellular organisms could grow, swim, crawl, fly, and evolve into everything else on Earth today.

It's nearly impossible to know how organisms first made the leap into multicellularity. But in an effort to look back in time, researchers in Japan bred collections of yeast cells that competed with each other for food. They found that the innovation of living as a group of cells would have given the first many-celled organisms a clear advantage--and that it may have been spurred by nothing more than sloppy wall building.

Yeast is a single-celled fungus, but in the wild it sometimes grows in clumps. This happens when a yeast cell clones itself, budding an identical "daughter cell," but fails to pinch the clone entirely free. These cells continue to reproduce, forming clumps. The researchers wondered if this incomplete separation of single-celled clones could have fostered the rise of multicellularity.

To find out, they first looked at individual yeast cells growing in an environment where their only food was sucrose, a sugar they have to break down before ingesting. To do this, the yeast secrete an enzyme called invertase that splits sucrose into its components, fructose and glucose, which the cell can then absorb. (One advantage of being a complex, multicellular animal is that we don't have to digest our food outside our bodies.) When the yeast cells were all alone, they struggled to survive in the all-sucrose environment. But when other yeast cells were nearby, they all benefited by absorbing the leftover sugars that escaped their neighbors.

Knowing that external digestion works better with friends around, the researchers hypothesized that clumps of yeast should be able to thrive where individual yeast cells can't. They genetically engineered yeast with a gene that encouraged clumping, rather than separation. As predicted, these clumpy yeast were able to grow in environments with a low concentration of food, where single yeast cells couldn't survive.

It takes work for yeast cells to make and secrete invertase, though. Cells that are unable to make invertase are called "cheaters" because they can sit back and enjoy (or absorb, at least) the fruits of their neighbors' external digestion. If they're all alone, these cheaters won't find enough food. But when they're around enough other single cells, the cheaters will outcompete the hard-working invertase producers.

To find out whether multicellularity would help yeast defend themselves against cheaters, the researchers arranged competitions between cheater yeast cells and non-cheaters, either alone or in clumps. At low food concentrations, the clumpy cells easily outcompeted the individual cells, ending up with higher numbers in their population. When cheaters were thrown into the mix, clumpy cells retained their advantage. All around, clumping was a better strategy.

The authors may have modeled the beginning of multicellularity--or one beginning, since the trait evolved multiple times. They showed that the need to digest your food externally is enough to give groups of cells an edge over single cells, and that the strategy of keeping your clones all in one place is enough to seize that advantage. When the first mutant cells failed to fully separate from each other, and found that their little family was now growing faster than the individual cells around them, it could have been the start of something big. (That is, visible without a microscope.)

They may be mere microscopic fungi, but a community of yeast cells has similarities to a community of animals, or even a city. Organisms live in groups when doing so helps them to get food, fend off predators, and pass on their genes. Even when our communities resemble disorganized, unsightly blobs, they're what keep our species alive.

H. Koschwanez, J., R. Foster, K., & W. Murray, A. (2011). Sucrose Utilization in Budding Yeast as a Model for the Origin of Undifferentiated Multicellularity PLoS Biology, 9 (8) DOI: 10.1371/journal.pbio.1001122

To Dyslexics, English Sounds like a Foreign Language

How well can you identify other people's voices? Most of us are good at recognizing a familiar speaker we can't see. This skill works best, though, in our native tongue. And to the ears of a dyslexic person, everyone else may as well be speaking Chinese.

Dyslexia is usually described as a reading disorder. In school, a dyslexic kid will struggle to recognize words and parse sentences. She (or more often, according to some studies, he) might have assignments read aloud or receive prewritten class notes.

Underneath this difficulty with reading, though, may lie a failure to correctly process the sounds that make up words. To explore this theory, researchers at MIT had 16 dyslexic adults and older teens, as well as 16 non-dyslexics, listen to a series of recorded sentences. The voices they heard belonged to ten males, five speaking English and five speaking Mandarin Chinese (a language none of the subjects was familiar with). Subjects were trained on a computer to associate each of the 10 voices with a cartoon avatar. Then the test began: subjects listened to a series of 50 sentences and had to pick the speaker for each one.

Non-dyslexic subjects were much better at identifying the speaker when the sentences were in English. They picked the right avatar (out of the five possible ones) about 70% of the time in English, and only about half the time in Mandarin. Dyslexics, though, experienced no advantage with an English-speaking voice. They identified English speakers and Mandarin speakers equally, at about 50%, precisely as if English weren't their native language. Furthermore, the subjects with the most severe dyslexia fared the worst at identifying English speakers.

Voice recognition, the authors say, depends on our ability to analyze the phonetic pieces within each word and compare them to what we expect to hear. Different people's pronunciations will deviate from our expectations in different ways. When we don't have any expectations about those sounds, though--say, if we're hearing an utterly unfamiliar language--we have a harder time comparing the voices of different speakers. A dyslexic person may be lacking that internal dictionary of sound blocks for his or her native language. Instead of being processed invisibly in the brain, words must be scrutinized and decoded. School begins to resemble a foreign-language immersion class.

Dyslexia can encompass a range of symptoms. A related diagnosis, and one that sometimes goes along with dyslexia, is dysgraphia: an impairment in writing, rather than reading. Here, it's described by a 12-year-old reader of the magazine I edit; she left this comment on a discussion thread about what it means to be normal.
hi i am desgrafic, no its not contages and it is most sertenitly not my name. is a lerning disability, not two sereus thogh. it makes it hard to picture things in the mind, spell, follow derections, read, and a few other things like i hand cordination. its twin is dislecseo, its basickly the same. this isn't a desese and it's farly comin, and the best thing is you can get over it. it just makes it so you have to wurk a lot harder. and oh, did i mention hand righting, near imposiblely illegable. i used to spell cow C-A-W becase thats how i fenedickly chuncked it. there are some spetule scools set up (mostly privit) which foces on these disibityis. unforchinitly there is no cure exept a magick pill we call persestence, tack twise dally.
This girl single-handedly cured me of my habit of fixing all our commenters' spelling errors. I did it to keep kids from picking on each other's mistakes. But as soon as she started commenting, I threw in the towel.

Aside from being daunted by the task of interpreting and correcting all her words, I liked her comments the way they were. She was able to compose mature, interesting sentences--so much for a "writing disorder"--but approached English with an almost poetic naiveté (i hand coordination!). What's charming to me, though, illustrates the cognitive reality for kids with these disorders: At a certain level, they have no native language.

Perrachione, T., Del Tufo, S., & Gabrieli, J. (2011). Human Voice Recognition Depends on Language Ability Science, 333 (6042), 595-595 DOI: 10.1126/science.1207327

Depression: A Case of the Non-Growing Neurons?

A mouse that's uninterested in new foods and tasty drinks and easily despairs in a challenging situation has more than a case of the blues. This is a strain of mouse created by Jason Snyder and his colleagues at the National Institute of Mental Health to model human depression. To bring on the mouse's symptoms, all that was necessary was to stop one part of its brain from creating new cells.

The researchers wanted to investigate the link between depression and the brain's ability to grow new neurons, called neurogenesis. Most of your brain cells are born before you are, but new neurons also appear throughout adulthood. One of the main sites of their creation is in the hippocampus, an area of the brain associated with memory and navigation. The hippocampus is one of the first regions ravaged by Alzheimer's disease. It's also home to a high concentration of stress hormone receptors, making it especially sensitive to their effects.

Stress and stress hormones (glucocorticoids) are known to slow down the growth of new brain cells in the hippocampus. But the hippocampus is also involved in dialing down the body's stress response. Would an adult brain that can't grow new neurons--an impairment that would especially affect the hippocampus--have an out-of-whack stress reaction to stress? And would it become depressive?

To find out, Snyder and his colleagues manipulated mouse genes to create the strain that couldn't grow new neurons in adulthood. In their day-to-day life, the transgenic mice (and their stress hormones) behaved normally. But when the researchers stressed the mice out by keeping them restrained for 30 minutes, their stress hormones stayed elevated for much longer than in normal mice. It seemed that a nongrowing hippocampus was specifically impairing how the mice reacted to stress.

The researchers found the same result when they used radiation to target neurogenesis in the precise brain region they suspected to be at work, an area inside the hippocampus called the dentate gyrus. This suggested that the symptoms in their mice came from a lack of neurogenesis in this small region specifically.

Next, the neurogenesis-deficient mice underwent several tests for depressive-like behavior. In one test, the mice were placed in an open space with food at its center. The transgenic mice went to investigate the food just as quickly as ordinary mice did. But when researchers stressed the mice out immediately beforehand (by restraining them, again), the transgenic mice were much slower to go to the food, or didn't investigate it at all. The ordinary mice, though, weren't bothered.

Another test involved sugar water, which mice, like soda-susceptible humans, usually prefer to plain water. The neurogenesis-deficient mice didn't care much about sugar water, a symptom the researchers say is comparable to anhedonia, the depressed person's inability to take pleasure from usually enjoyable activities.

Finally, the mice were tested for "behavioral despair," rather upsettingly described here:
We next tested depressive-like behavior, using the forced swim test, in which rodents are placed in an inescapable cylinder of water and immobility is used as a measure of behavioral despair.*
In their inescapable water tank, the transgenic mice gave up and stopped swimming sooner than normal mice. They also stayed immobile for longer periods. (After the test, mice were dried off and placed in a heated cage to recover.)

It seems, then, that not being able to create new cells in the hippocampus exaggerates the stress response (as in the forced swim test, and the tests done after restraining the mice) and makes mice lose interest in pleasurable activities.

Neurogenesis is needed to buffer the stress response--but neurogenesis itself is impaired by stress. If their mouse model is a fair approximation of depression, the researchers speculate, maybe depressive symptoms are the result of a bad feedback loop: stress impairs neurogenesis, which in turn makes a person more reactive to stress. Future research may show that the ability to grow new brain cells is an important factor in human depression. A predisposition to overreact to stress hormones, or a sluggishness in generating new neurons, might be what leads a human adult to the feeling that they'll never swim out of the tank.

Snyder, J., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. (2011). Adult hippocampal neurogenesis buffers stress responses and depressive behaviour Nature DOI: 10.1038/nature10287

*This sort of treatment is what might encourage a group of NIMH rodents to run away and create their own organized society under a rosebush somewhere.

Superheroes Who Share a Power with Dolphins

If only for reasons of terrestrial mobility, you probably shouldn't populate your whole superhero squad with cetaceans. Evil lairs on land would be difficult for you to infiltrate, to say the least. But you'd do well to consider including a dolphin or two in your next hero league. Dolphins were all over science journals last week, displaying powers that could put certain superheroes out of business.

A letter published in Nature's Journal of Investigative Dermatology pointed out that bottle-nosed dolphins have remarkable healing abilities. They have plenty of run-ins with sharks: one survey found that 40% of dolphins had visible shark-bite scars. But all of these wounds had healed without killing the dolphins from blood loss or infection.

The author, Michael Zasloff, also cites observations of dolphins healing in captivity. Despite having wounds a foot long and more than an inch deep--reaching all the way through their skin and blubber--these dolphins were as good as new just four weeks later. What's more, they showed no signs of pain while they went about their business.

Setting aside the mystery of their apparent lack of discomfort, how do dolphins prevent massive blood loss after having a foot-wide bite taken out of them? It's not clear, especially since their blood actually clots less readily than ours. A further mystery is how they avoid infection. Swimming around in seawater is pretty much the opposite of the advice humans get from their doctors to keep a wound clean and dry.

Zasloff speculates that some component of dolphin blubber acts to prevent infection. He suggests a certain molecule called isovaleric acid, which dolphins create within their blubber. It's known that this fatty acid accumulates in the blubber and doesn't get burned up for fuel during times of starvation. The molecule is also known to have antimicrobial powers. Perhaps, Zasloff says, isovaleric acid is released from the blubber after a serious injury and protects the surrounding tissue from infection.

Whatever factors give dolphins their healing superpowers, humans would love to go Rogue and borrow a little for ourselves.

Iron Man
Who needs special healing abilities when you have the brains and resources to build yourself a protective suit? Bottlenose dolphins living in Shark Bay, Western Australia, have come up with a clever way to forage for food. They tear up basket sponges that are unfortunate enough to be living near them, like this one:

Then they convert those hapless sponges into protective face-masks:

The "spongers" swim along the seafloor and poke around with their sponges until they disturb a fish hiding under the rocks there. Then they ditch the sponge and snag their prey.

The seafloor in Shark Bay is littered with shards of shell, rock and coral that could scratch dolphins' skin. So the sponges seem meant to protect dolphins' beaks while they ferret out food. But researchers from Georgetown University wondered why dolphins would bother to go digging for food with their faces when they already possess the power (shared by Daredevil) of echolocation. Since they can hunt effectively with sound, why do these dolphins hunt with sponges?

To find out, the researchers gamely attached a sea sponge to a pole and began poking around the seafloor with it, emulating a sponge-hunting dolphin. Whenever a fish popped out of the rubble, they caught it and identified its species. They discovered that the fish species hiding under the rocks were less likely to have the balloon-like organ called a swim bladder. This lack of an airy center, along with their rubbly hideout, makes the fish harder to detect by echolocation.

The "sponging" behavior is mostly seen in female dolphins, who teach it to their daughters. Obvious Eline Benes jokes aside, it's a clever solution for reaching a food source the dolphins couldn't otherwise get to. 

Another way to find food that's well hidden--if your food is a living animal, anyway--is to sense the electrical field around its body. All animals generate faint electrical fields, thanks to the currents running through our nerves and muscles. A group of German researchers has discovered that the Guiana dolphin, a species living off the north and east coasts of South America, is able to perceive these electrical fields.

The researchers examined dark pits on the dolphins' snouts that were thought to have no function--they're remnants of the holes whiskers grow out of in some other mammals. Rather than being useless, the researchers found, these pores have evolved into active sensors for electric fields. To test how sensitive the dolphins were to the kinds of electric fields their prey might give off, researchers taught a captive dolphin to hold its beak inside a hoop. When it felt an electric current near its beak, the dolphin was trained to signal the researchers by swimming away from the hoop. (This sounds like a more-fun version of the hearing tests given to kids: If you hear a beep, run!)

The dolphin could reliably sense electrical signals like those given off by its prey fish. The researchers think this ability might help supplement the Guiana dolphins' echolocation abilities, since they tend to live in murky waters and hunt for fish that live in mud.

Dolphins aren't the only animal with an electric sense. Many fish and some amphibians have also evolved the ability to perceive electrical fields in water. Among mammals, the power had only previously been observed in the echidna and platypus--weird egg-laying mammals that, superhero or not, would have a home on any team of mutants.

Zasloff, M. (2011). Observations on the Remarkable (and Mysterious) Wound-Healing Process of the Bottlenose Dolphin Journal of Investigative Dermatology DOI: 10.1038/jid.2011.220

Patterson, E., & Mann, J. (2011). The Ecological Conditions That Favor Tool Use and Innovation in Wild Bottlenose Dolphins (Tursiops sp.) PLoS ONE, 6 (7) DOI: 10.1371/journal.pone.0022243

Czech-Damal, N., Liebschner, A., Miersch, L., Klauer, G., Hanke, F., Marshall, C., Dehnhardt, G., & Hanke, W. (2011). Electroreception in the Guiana dolphin (Sotalia guianensis) Proceedings of the Royal Society B: Biological Sciences DOI: 10.1098/rspb.2011.1127