Saint Bartholomew Exorcising, circa 1440-1470 (Google Art Project, via Wikimedia Commons)

“Historically, many cases of demonic possession have masked major psychiatric disorder[s].”-Kazuhiro Tajima-Pozo et. al. BMJ Case Reports 2009

Portrait of Joan the Mad by Juan de Flandes, circa 1496 - 1500 (Gallery of Web Art, via Wikimedia Commons)

“Juana (also known as Joanna and Joan) of Castile was born in Toledo, Spain on 6 November 1479, the third child of Queen Isabella of Castile and King Ferdinand II of Aragon. Not long after her marriage to Philippe “The Handsome,” Duke of Burgundy, people of the court began referring to her as Juana “The Mad” (la loca)…

Juana’s life became far more complex than her parents or her contemporaries could have anticipated. As a young woman she was described by ambassadors to the Spanish court as beautiful and highly educated. She spoke six languages, was accomplished in religious studies, court etiquette, dance, and music. She was a capable equestrian. Then, in a twist of fate, through her inheritance and marriage she became the foundation of what was to be the most powerful kingdom in the world of the sixteenth century, and the most extensive the world has known…

Juana’s story is tragic. There was so much to be gained by others and so much to be lost by her. Her marriage, her inheritance, her children all became personal tragedies…popular culture has depicted Juana as a schizophrenic who had an obsessive attachment to her deceased husband and a victim of those in power around her. Juana was the rightful heir to her mother’s kingdom of Castile-Leon and all its possessions. Rather than a place on her rightful throne, she ended up confined to a room in a remote castle with only her youngest child to keep her company.”

–Juana “The Mad” Queen of a World Empire By Linda Andrean, Center for Austrian Studies. October 2012

Extraction of the Stone of Folly by Hieronymus Bosch circa 1488 - 1516 (www.rijksmuseum.nl, via Wikimedia Commons)

“Bosch’s fool is appealing to a surgeon to extract a stone from his head. The stone in question is the “stone of folly” or “stone of madness” which, according to popular superstition, was a cause of mental illness, depression, or stupidity. Such stones could be located anywhere in the body, such as the bowels or back, but were most commonly assigned to the head, where a surgeon would have to cut into the skull to remove them.” –“The Stone of Madness.” Jessica Palmer in Bioephemera, August 2008

The Madhouse by William Hogarth, 1773 (The Yorck Project, via WikiPaintings)

“The eight paintings in William Hogarth’s A Rake’s Progress (1733) tell the story of Tom Rakewell, a young man who follows a path of vice and self-destruction after inheriting a fortune from his miserly father. It was Hogarth’s second ‘modern moral subject’, and followed the hugely successful A Harlot’s Progress (1730)…

In the concluding scene Tom has descended into madness and is now in Bethlem Hospital or Bedlam as it was known. He is surrounded by other inmates who are suffering various delusions. These include a tailor, a musician, an astronomer and an archbishop. In the door to one of the cells is a man who thinks he is a king – he is naked and carries a straw crown and sceptre. Like the real Bedlam, Hogarth’s Madhouse is open to the public. Two fashionable ladies have come to observe the poor suffering lunatics as one of the sights of the town. The ever-faithful Sarah Young sits, weeping, by Tom’s side.” - “A Rake’s Progress” Sir John Soane’s Museum

The Madhouse by Francisco de Goya, circa 1812 - 1819 (Web Gallery of Art, via wikimedia Commons)

“The problems of the mentally ill have challenged both society and physicians for centuries. In times past their odd behaviour often associated with insanity was interpreted as the result of demonic possession. It could also, sometimes, be a source of public amusement. To control their behaviour the insane were often manacled. This appalling state of affairs is well illustrated in this work by Goya (1746–1828). He was not the first or last to depict the institutionalized insane (for example, Hogarth’s Bethlem Hospital in 1735 and Chepik’s The Madhouse in 1987), but Goya’s work certainty evoked the suffering and torment of these individuals. Interestingly, Goya had been taken seriously ill in 1792 at the age of 47 with loss of balance, difficulty in walking, partial blindness and deafness. It has been suggested that this could have been a viral-induced Vogt–Koyanagi–Harada syndrome. Over the following months he gradually recovered but remained permanently deaf. This harrowing illness may well have had an influence on his later work. It is also quite possible he had a fear of insanity himself because two of his relatives (an aunt and uncle) were affected in this way.” -Alan E. H. Emery, Practical Neurology. June 2008

Salpêtrière by Armand Gautier, circa 1857 (Wikimedia Commons)

“1857 lithograph by Armand Gautier, showing personifications of dementia, megalomania, acute mania, melancholia, idiocy, hallucination, erotomania and paralysis in the gardens of the Hospice de la Salpêtrière. Reprinted in Madness: A Brief History (ISBN 978-0192802668), from which this version is taken.”

Portrait of a Woman Suffering from Obsessive Envy by Théodore Géricault circa 1881 (Wikimedia Commons)

“Gericault’s Monomaniac series once consisted of ten portraits of the mentally ill, however, only five have survived into the present day. The surviving paintings include the Monomanie du commandment militaire (Napoleonic veteran suffering from the delusion of military authority), Monomanie du vol des enfants (A compulsive kidnapper), Monomanie du vol (A kleptomaniac), Monomanie du jeu (A compulsive gambler) and Monomanie de l’envie (A woman suffering fits of neurotic jealousy).

The term ‘monomania’ was first coined by French psychiatrist Jean-Etienne Esquirol, and it was an exclusively nineteenth century term referring to a person who was outwardly well, but harboured one obsessive fixation. The portraits themselves and the context within which they were painted raise many questions regarding the state of psychiatry and the treatment of the mentally ill at the time, the public’s view of the mentally ill, the progression of science and the morbidity and tragedy that art encompassed during this period. The reason for the portrait’s creation can be interpreted in a number of ways, ranging from the rarer thought that it was encouraged as a therapeutic exercise for Gericault by his psychiatrist, to the more widely received idea that the paintings were produced as part of a commission from psychiatrist Dr Etienne-Jean Georget.” -Kate Davey, Outsider Art. January 2012; see also “Géricault’s Portraits of the Insane” by Ben Pollitt, Smarthistory

Philippe Pinel à la Salpêtrière by Tony Robert-Fleury, circa 1876 (medarus.org, via Wikimedia.commons)

“Completed more than three quarters of a century after the event, it portrays several stock figures in the tradition of asylum art: a woman (on the ground) tearing at her clothing, 2 huddled melancholics, a tense maniac, and a woman (at right) with a vacant stare chained to the wall. In the center is a limp and passive woman, whose stance emphasizes her unthreatening nature. She is being freed from her chains as the commanding figure of Dr Philippe Pinel looks on.

This scene in Robert Fleury’s painting is often said to have taken place during the French Revolution as a psychiatric parallel to larger political events: the rights of man extended to the (female) inmates of a mental asylum. In fact, however, Pinel unchained the female patients at Paris’s Salpêtrière hospital in 1800. He did not entirely abandon physical restraints, but when necessary, he confined the more agitated and potentially dangerous patients to the gentler control of the recently popularized strait-jacket. This was part of a widespread asylum reform movement that began during the late 18th century and continued well into the 19th.

Lay asylum superintendents and early medical “alienists” (psychiatrists) in Italy, England, France, and the United States contributed to humanizing the treatment of the insane by making confinement less brutal and treatment more gentle and interactive. Pinel in particular spent a great deal of time with his patients, listening attentively as he recovered their life histories. His was a newly sympathetic attitude toward the insane: he tried to make contact with their remaining vestiges of reason, rationally reconstruct their mental world, and—after a momentary act of identification—lead them back to sanity.”–“Freeing the Insane.” Elizabeth Fee and Theodore Brown. American Journal of Public Health. October 2006

Reproduction of Vincent Van Gogh's Self-Portrait With A Bandaged Ear, circa 1889 (allartpainting.com via Wikimedia Commons)

“‘Self-Portrait with a Bandaged Ear’ was painted after Van Gogh began to suffer from serious mental illness, including psychotic episodes and delusions. The painting was directly motivated by a psychotic attack, during which Van Gogh chased and threatened Gauguin with a knife. Immediately following this episode, Van Gogh returned home, cut his ear off, and offered it to a prostitute as a gift.

After his hospitalization, Van Gogh discovered that Gauguin had left Arles and that Van Gogh’s dreams of forming an artistic community had been destroyed by his own behavior. After suffering a nervous breakdown, he checked himself into a sanatorium. In 1890, Van Gogh succumbed to his illness and depression. He shot himself in the chest and died two days later.”-NYU School of Medicine

The Scream by Edvard Munch, circa 1893 (WebMuseum at ibiblio via Wikimedia Commons)

“One evening I was walking along a path, the city was on one side and the fjord below. I felt tired and ill. I stopped and looked out over the fjord—the sun was setting, and the clouds turning blood red. I sensed a scream passing through nature; it seemed to me that I heard the scream. I painted this picture, painted the clouds as actual blood. The color shrieked. This became The Scream.”-Evdard Munch

“Depersonalization [disorder], a serious disruption in a persons thoughts or sensations about their individual self, understandably alters their entire world…Alienation, isolation, and altered perceptions have for centuries served as themes for the visual arts, particularly modern art. Edvard Munch’s famous painting The Scream depicts the essence of a private hell and detachment from all things outside of one’s self.”-Feeling Unreal: Depersonalization Disorder And the Loss of the Self By Daphne Simeon & Jeffrey Abugel

“The world’s most famous panic attack occurred in Olso during January 1892…This experience affected the artist so deeply he returned to the moment again and again, eventually making two paintings, two pastels, and a lithograph based on his experience, as well as penning a poem derived from the diary entry. While it isn’t known if Munch had any more panic attacks, mental illness did run in his family; at the time of his episode, his bipolar sister was in an asylum.”-Kathy Benjamin, Mental Floss. September 2012

Portrait of German writer Heinrich Mann by Max Oppenheimer, circa 1910 (Wellcome Collection via Wikimedia Commons)

“Max Oppenheimer seriously rivalled Kokoschka as a portrait-painter. In 1911, rows erupted between the two artists over who could lay claim to the invention of the ‘psychological portrait’. Oppenheimer’s depiction of the German novelist Heinrich Mann in a state of nervous enervation, with flickering eyelids, rigid limbs and splayed fingers, was declared a “Kokoschka-copy”. Heinrich was brother to Thomas Mann, who continually engaged with the themes of mental illness, incarceration and freedom in his fiction writing.”–Wellcome Collection

Jackson Pollock’s Psychoanalytic Drawings, circa 1939-40 (via Duke University Press)

“Perhaps no aspect of Jackson Pollock’s oeuvre—one of the most important American artists of the twentieth century—has been more misunderstood than the drawings Pollock created during Jungian psychoanalysis sessions from 1939–40. Presented to his psychotherapist, where they remained in private files for almost three decades until their publication in 1970, these drawings have been shrouded in both personal and art-historical controversy—from a lawsuit filed by Pollock’s widow, Lee Krasner, to wide-ranging justifications of them as Jungian iconography or as “proof” of Pollock’s supposed mental disorder…

The images reveal a range of styles, from highly refined and elaborate sketches to rapid and automatic improvisations, as well as a range of subjects, from human figures, animals, and cryptic figures to purely abstract forms. Together, they bear witness to Pollock’s intense interest in the latest contemporary art as well as non-Western traditions…Remarkable for their beauty as well as spontaneity, these drawings reflect the conscious intellectual choice of an artist blazing new trails.”–Duke University Press

Rhythm 2 by Marina Abramovic, circa 1974 (via mikkipedia)

“As an experiment testing whether a state of unconsciousness could be incorporated into a performance, Abramović devised a performance in two parts.In the first part, she took a pill prescribed for catatonia, a condition in which a person’s muscles are immobilized and remain in a single position for hours at a time. Being completely healthy, Abramović’s body reacted violently to the drug, experiencing seizures and uncontrollable movements for the first half of the performance. While lacking any control over her body movements, her mind was lucid, and she observed what was occurring.

Ten minutes after the effects of that drug had worn off, Abramović ingested another pill – this time one prescribed for aggressive and depressed people – which resulted in general immobility. Bodily she was present, yet mentally she was completely removed. (In fact, she has no memory of the lapsed time.)”-Wikipedia; see also Lisson Gallery

“Bobby Baker is one of the most widely acclaimed and popular performance artists working today. She began her diary drawings in 1997 when she became a patient at a day centre. Originally private, they gradually became a way for her to communicate complex thoughts and emotions that are difficult to articulate to her family, friends and professionals.

The drawings cover Bobby’s experiences of day hospitals, acute psychiatric wards, ‘crisis’ teams and a variety of treatments. They chart the ups and downs of her recovery, family life, work as an artist, breast cancer and just how funny all this harrowing stuff can be.”–Wellcome Collection

This post inspired by “Depictions of Mental Illness in the History of Art,” a recent presentation by Fernando Espi Forcen and Carlos Espi Forcen at the 2013 annual meeting of the American Psychiatric Association in San Francisco

Source: CDC, via Wikimeda Commons

SAN FRANCISCO—Standing at a podium in front of an audience of psychiatrists, clinicians and scientists, Firdaus Dhabhar brings up a video of his infant son on a large projector screen and presses play. Smiling and wriggling, Dhabhar’s son rests on his back in a doctor’s office—perfectly content. “Watch for the immediate reaction,” Dhabhar tells the audience. A nurse expertly injects his son’s thigh with a vaccine. For half a second, nothing changes. Then the child stops moving; his eyes widen; his face twists into misery as he begins to cry. Meanwhile, the nurse has not missed a beat, injecting several more vaccines. As she leaves she turns to the camera and says, “Sorry I couldn’t make him cry more.”

Dhabhar likes to film babies crying when they get their shots; he knows that the wailing is a good sign—so do the nurses in the hospitals he frequents. A Stanford University researcher who studies how stress changes the body, Dhabhar and his colleagues have discovered that subjecting mice to minor stress before they are vaccinated boosts the immune system and makes the vaccines more effective. Mice that were stressed out prior to their inoculations had an easier time overcoming a subsequent infection than mice that the researchers left in peace before their shots. Something similar seems to happen to people. In a study of knee surgery patients, for example, Dhabhar and his teammates found that anticipating surgery increases the number of immune cells circulating in the bloodstream in the days preceding the operation. Studies like these have convinced Dhabhar that stress does not entirely deserve its bad reputation, which was one of the main messages of his recent presentation at the annual meeting of the American Psychiatric Association in San Francisco. Some kinds of short-term stress—as opposed to chronic stress—can improve health.

From an evolutionary perspective, the fact that short-term stress revs up the immune system makes sense. Consider a gazelle fleeing a lioness. Once the gazelle’s eyes and ears alert its brain to the threat, certain brain regions immediately activate the famous fight-or-flight response, sending electrical signals along the nervous system to the muscles and many other organs, including the endocrine glands—the body’s hormone factories. Levels of cortisol, epinephrine, adrenaline and noradrenaline rapidly increase; the heart beats faster; and enzymes race to convert glucose and fatty acids into energy for cells. All these swift biological changes give the gazelle the best chance of escape. At the same time, Dhabhar and others’ research suggests, the brain’s recognition of a threat prompts the immune system to prepare for potential injury. The spleen and other organs release immune cells specialized for identifying and destroying invaders and healing damaged tissues. After all, even if the gazelle escapes with its life, it may need to heal wounds sustained during its flight and prevent them from becoming infected.

Somewhat paradoxically, cortisol—one of the hormones released during the fight-or-flight response—has long been known to suppress the immune system. Likewise, many people who are continually stressed over long periods of time have unusually low levels of immune activity. But then again, chronic stress can exacerbate allergies, asthma and autoimmune disorders in which the immune system is already overactive. So does stress excite or repress the immune system? Here’s where things get even more complicated, as they so often do in biology. The condensed answer is that it all depends on the situation and on the individual. Often, short-term stress activates certain parts of the immune system, but not all its components; in general, chronic stress stifles the immune system, but it may also make it more likely to attack benign tissues. In the study with knee surgery patients, people’s immune systems did not all respond to anticipation of the operation in the same way. Some people showed an adaptive response: the number of immune cells in their bloodstream increased in the days before the operation, then decreased as those immune cells migrated to the skin, lymph nodes, mucus membranes and other important sites of battle and repair. Other patients had a maladaptive response: their levels of circulating immune cells hardly increased or even dipped below their baseline level. As you might expect, people with an adaptive immune response recovered from surgery more quickly and more fully than people with a maladaptive response.

In recent decades, it has become increasingly clear that stress changes people’s health in subtle and obvious, temporary and enduring ways. In fact, depression and related illnesses may be—at least in part—disorders of handling stress. We all come into the world having inherited genes that partially determine how well we deal with stress. As we grow, our experiences bolster or weaken our innate resilience. For some people, a series of mildly stressful events may be enough to trigger depression or another illness; others will remain resilient through years of chronic stress. It will likely take decades of new research to understand such differences in detail. For now, though, we can at least be sure that it’s okay to feel stressed when you get a shot—in fact, it’s a good thing.

(Credit: Ferris Jabr)

This month the American Psychiatric Association will publish the latest edition of its standard guidebook for clinicians, the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5). In somewhat the same way that a field guide to birds helps people distinguish different species with illustrations and descriptions of physical features—a beak’s hooked tip, a blush of red plumage—the DSM helps clinicians recognize different mental illnesses with lists of typical symptoms, such as insomnia, low mood and hallucinations. The difference is that, whereas generations of biologists and birders have confirmed the existence of the animals they study—taking their pictures, holding them in their hands, comparing their DNA letter by letter—no one knows whether the disorders in the DSM are real.

Let me be clear: mental illness is real, but the discrete categories of illness in the DSM might not exist outside its pages. Are some people tired and miserable most of the time, plagued by spiraling thoughts of hopelessness and helplessness, unable to sleep—or sleeping too much—and uninterested in almost everything that once gave them pleasure, including sex? Absolutely. Their illness is real. Do all such people have a single disease that the DSM names depression? Probably not. Depression as defined by the DSM is a way of thinking about such symptoms. The DSM is not a catalogue of well-understood diseases with known causes that clinicians can identify with reliable diagnostic tests. It’s a book of useful concepts about some of our most complex and perplexing illnesses. It’s what we have to work with.

The American Psychiatric Association (APA) knows this. So does every major mental health organization, including the National Institute of Mental Health (NIMH). Recently, New Scientist, MIT Technology Review, Mind Hacks, The Verge and others—including my colleague John Horgan—proclaimed that the NIMH has suddenly decided to abandon, ditch or otherwise reject the DSM. This is a misunderstanding. Saying that the NIMH is rejecting the DSM is nonsensical. The fact is that psychiatrists need a common language in which to talk about their patients and the DSM—along with the similarly categorical International Classification of Diseases (ICD)—is the best guidebook available. In many cases, insurance companies require official DSM diagnoses before they help cover the costs of therapy and medication; the courts consider DSM definitions when discussing someone’s mental state; and the government still depends on the DSM when deliberating eligibility for disability benefits. None of that has changed.

NIMH has, however, been working on an endeavor known as the Research Domain Criteria Project, or RDoC for short, which encourages psychologists, neuroscientists and other scientists to think outside the DSM box—to begin transitioning away from established DSM disorders and instead study fundamental biological and cognitive processes underlying mental illness. The important distinction here is between clinical practice and research. The NIMH is not in any way saying that clinicians should stop using the DSM, but it does think that the DSM has constrained research. For a long time, scientists studying mental illness have found it much easier to get grants if they investigate an official DSM disorder and recruit participants who meet all the criteria for that disorder, rather than studying symptoms or unusual behavior not already sanctioned by the DSM. NIMH wants to change that by funding studies that are not strictly bound by the DSM‘s definitions.

Given that DSM disorders are useful inventions that do not perfectly mirror the reality of mental illness—or, in some cases, do not reflect its reality at all—the idea is to use modern tools to identify specific changes in the brain’s structure and behavior that at least partially explain the various symptoms of different mental illnesses. As I wrote in the May issue of Scientific American, “Some scientists might explore how and why the neural circuits that detect threats and store fearful memories sometimes behave in unusual ways after traumatic events—the kinds of changes that are partially responsible for post-traumatic stress disorder. Others may investigate the neurobiology of hallucinations, disruptions in circadian rhythms, or precisely how drug addiction rewires the brain.” RDoC is not a brand new development—it began in 2009—and it will continue for at least another decade. In the long-term, RDoC will hopefully improve not only diagnosis of mental illness, but also its treatment, by providing new specific biological targets for medication.

As far as I can tell, the recent confusion in the media began as a misinterpretation of Thomas Insel‘s April 29th blog on the NIMH website. Insel, Director of NIMH, and his colleague Bruce Cuthbert, Director of the Division of Adult Translational Research, are leading RDoC. Nowhere in his blog does Insel say he is abandoning the DSM, but he does make it clear that “the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure,” that “patients with mental disorders deserve better” than the DSM and that “NIMH will be re-orienting its research away from DSM categories.” None of this is particularly shocking to professional psychiatrists or anyone even moderately acquainted with psychiatry. I think the leaders of the APA would agree with just about everything Insel wrote. In fact, the NIMH and APA plan to collaborate to transform psychiatric diagnosis. RDoC is meant to help rewrite the DSM, not abolish it.

I got in touch with both Insel and Cuthbert to further clarify the matter. “The sensationalist headlines out there are entirely misleading, and we will continue to support DSM-based research as we increase our portfolio of RDoC grants,” Cuthbert wrote in an e-mail. “RDoC is intended to inform future versions of the ICD and DSM; we have no intention of coming out with a competing system. The implication of this is that the fruits of RDoC are likely to be taken up into the ICD/DSM piecemeal rather than in one entire set, at such times as the evidence for various aspects becomes strong enough to warrant changes to the nosologies.”

Insel echoed these comments in a separate e-mail: “We cannot ‘ditch’ or ‘reject’ terms like schizophrenia or bipolar. We just need to view them as constructs, perhaps including many different disorders that require different treatments or obscuring disorders than cut across the current categories. A symptom-only system will not be sufficient for identifying brain disorders—whether the initial label is dementia or schizophrenia.”

When censure comes easily, it is dangerously seductive. People get something akin to schadenfruede out of condemning the DSM and all of modern psychiatry along with it. Super important government institution rejects psychiatry’s beloved Bible! Psychiatrists in crisis. Everything will change. It’s so easy to tweet and retweet hyperbolic claims—or post a link on Facebook—before really understanding the issues. Something big is happening. I must be a part of it. But such sensationalism obscures the truth. The DSM is severely flawed, but it has improved over time; so has psychiatry. “Schizophrenia remains an immensely useful construct–imperfect for sure, but very helpful in clinical communication and in guiding treatment,” writes Allen Frances, a professor emeritus at Duke University, North Carolina, the chairman of the DSM-IV task force and one of the DSM-5‘s most vociferous critics. “The DSM disorders are all fallible and subjective constructs, but most are useful as temporary way stations until we learn more and can develop better ones.”

In so many of the recent critical articles about the DSM-5, the ironic implication is that abandoning the DSM is the right thing to do—that it’s a drastic but necessary move in order to help people with mental illness. Really? Abruptly abandoning the DSM would not help anyone. Fortunately that’s not what is happening.

A screenshot from Andrew Irving's "New York Stories: The Lives of Other Citizens"

On any given day, millions of conversations reverberate through New York City. Poke your head out a window overlooking a busy street and you will hear them: all those overlapping sentences, only half-intelligible, forming a dense acoustic mesh through which escapes an exclamation, a buoyant laugh, a child’s shrill cry now and then. Every spoken consonant and vowel begins as an internal impulse. Electrical signals crackle along branching neurons in brain regions specialized for language and movement; further pulses spread across facial nerves, surge toward the throat and chest and zip down the spine. The diaphragm contracts—pulling air into the lungs—and relaxes, pushing air into that birdcage of calcium and cartilage—the larynx—within which wings of tissue draw near one another and hum. As this vibrating air enters the mouth, the tongue guides its flow and the lips give each breath a final shape and sound. Liberated syllables travel between one person and another in waves of colliding air molecules.

All these conversations are matched in number and complexity by much more elusive discourses. The human brain loves soliloquy. Even when speaking with others—and especially when alone—we continually talk to ourselves in our heads. Such speech does not require the bellows in the chest, quivering flaps of tissue in the throat or a nimble tongue; it does not need to disturb even one hair cell in our ears, nor a single particle of air. We can speak to ourselves without making a sound. Stick your head out that same window above the crowded street and you will hear nothing of what people are saying to themselves privately. All that inner dialogue remains submerged beneath the ocean of human speech, like a novel written in invisible ink behind the text of another book.

Some people have tried to eavesdrop on the silent conversations in other people’s minds. Psychologists have attempted to capture what they call self-talk or inner speech in the moment, asking people to stop what they are doing and write down their thoughts at random points in time. Others have relied on surveys or diaries. Andrew Irving, an anthropologist at the University of Manchester, decided to try something a little different: a peripatetic transcription of consciousness.

While completing his PhD in the 1990s, Irving became interested in how people’s thoughts, especially their perception of time, change as they approach death. He gave volunteers with serious or terminal illnesses voice recorders and asked them to walk around their neighborhoods, speaking their thoughts out loud. In effect, he turned each of his volunteers into an amanuensis of his or her own chattering mind. “I realized that you could see somebody sitting in a chair or walking along the street and it may seem like nothing much is happening—but actually an incredible amount is happening,” Irving says. “In their heads they may be going from childhood to religion to questioning God to trying to imagining what exists beyond death.”

More recently, Irving received a grant to track down these volunteers and find out what happened to them. As a side project, he decided to record the inner dialogues of people walking in New York City—to map part of the city’s thoughtscape, layered beneath its audible soundscape. He approached strangers at different points in the city. “Excuse me,” he would say, “this might sound like a strange question, but can I ask you what you were thinking before I stopped you?” If the stranger did not run away, he would ask them to wear a microphone headset attached to a digital recorder and speak aloud their thoughts as he followed closely behind with a camera. He would not be able to hear what they were saying, Irving explained, and they would be free to walk wherever they liked and continue their business as usual.

“I was surprised by how many said Yes,” Irving says—about 100 in all. By overlaying the recorded audio onto the videos, he has created portraits of individual consciousnesses on a particular day in New York City—transcripts of people’s inner dialogues that remind one of works by Virginia Woolf, James Joyce and other writers who were especially interested in recreating the mind on the page. He calls the project “New York Stories: The Lives of Other Citizens.” Different videos focus on different parts of the city, such as streets, bridges, squares and cafés.

Irving’s videos are simultaneously naturalistic and as objective as possible. In the lab, in front of a researcher, people are often reluctant to reveal exactly what they are thinking. Writing a diary of inner speech is somewhat more private, but many people find it annoying to regularly drop everything and make an entry; sometimes it’s difficult to remember what one was thinking about even minutes earlier. In Irving’s videos people are living their lives more or less as usual, walking and talking to themselves as though they were unaccompanied. Of course, people who are not completely comfortable with the scenario sometimes speak into the microphone as though trying to entertain someone else. And getting people’s inner speech on tape captures only linguistic forms of thought, neglecting the kind of thinking that happens in images and scenes, for example. Still, Irving’s videos are permanent records of fleeting thoughts, of dynamic mental processes unfurling in real time. They give us nearly direct access to a kind of internal communication we usually do not share with one another.

In one video, a young woman named Meredith walks along Prince Street in downtown Manhattan. She briefly wonders if there’s a Staples nearby before reminiscing about a recent visit to her friend Joan, whom, we learn, has cancer. Meredith contemplates her friend’s situation for the next two minutes, tearing up at the thought of “New York without Joan.” Abruptly, she notices a café where she used to sit and people watch, laments how it has changed and resumes her search for a Staples. Fewer than 30 seconds later, she is talking to herself about Joan again—but serious reflection on mortality is punctuated by more provincial thoughts about navigating the crowds. When she remembers how bluntly and simply Joan announced her cancer, Meredith begins to choke up—then interrupts herself with a little burst of frustration while crossing the street: “What is this craziness? Five cars in the middle.” The segment ends with Meredith asking herself, once again, whether she is any closer to a Staples.

Meredith’s meandering thoughts recall Clarissa Dalloway’s roaming mind in Virginia Woolf’s novel Mrs. Dalloway. As she walks the streets of London, Clarissa entertains an ephemeral memory of throwing a shilling into the Serpentine, before transitioning to a more somber meditation on death: “Did it matter then, she asked herself, walking towards Bond Street, did it matter that she must inevitably cease completely; all this must go on without her.” Moments later she is commenting to herself on books in a shop window, then deriding her “pea-stick figure,” then admiring a fishmonger. She converses with herself about war, immortality, past romances and what kind of flowers she should buy for her party.

Woolf would likely have adored Irving’s videos. She wanted to write about “an ordinary mind on an ordinary day.” As opposed to many of her contemporaries, she was far more interested in what was happening inside people’s heads—in thought, memory and consciousness—than in detailed descriptions of buildings, countenances and clothes. She wanted the reader to perceive almost everything through her characters’ minds, rather than dictating a traditional plot with third-person narration. Like a telepathic moth, the narrator in Mrs. Dalloway flits from one person’s consciousness to another as they go about their business in London. Though the characters do not know it, their minds ring with echoes of one another’s inner speech: even when apart, they think of the same events at the same time—of Big Ben’s gonging or a car backfiring like a pistol; they constantly think of each other and lose themselves in memories of shared experiences.

“There’s always this assemblage of voices simultaneously going on in public all the time—but you can’t hear it,” Irving says. “I’m interested in whatever people are thinking about. ‘What should I buy for dinner tonight? Should I buy pasta?’ That’s just as interesting to me as something more dramatic.”

Andrew Irving would like to acknowledge that his research was funded by the ESRC (UK) and Wenner Gren Foundation (New York)

Dear Miss Austen,

It is an immense honor to be addressed by you.  However, I worry that the letter addressed to me was written not by one of the greatest writers in the English language but by an impersonator, because the Austen that the world knows and loves is a great reader.  The letter recommends reading your novels before reading books about your novels, and of course I agree.  But the person who wrote the letter shows little evidence of either.

For example, the letter states that in Persuasion, Anne Elliot breaks her engagement with Captain Wentworth because of the wishes of “her relatives.”  It is true that Anne’s father, Sir Walter, is against the marriage, but you make quite clear that the decisive opinion is that of Lady Russell: “Young and gentle as she was, it might yet have been possible to withstand her father’s ill-will . . . but Lady Russell, whom she had always loved and relied on, could not, with such steadiness of opinion, and such tenderness of manner, be continually advising her in vain.”  Unfortunately, Lady Russell is not a relative.

The letter thus makes a factual error unworthy of anyone who claims close knowledge of your novels.

The error of not reading my book is not at all comparable to the error of not reading yours, and I apologize for burdening you with this discussion.  The letter quotes from my book, but only from the first chapter; thus I am in the position of a chef who has been judged by her menus, not her food.

If the person who wrote the letter had read past the first chapter of my book, he would understand, for example, that when I write that a person chooses according to her preferences, those preferences can take into account many things, including her financial situation.  I cover this in the second chapter; this is the standard usage of the term “preferences” in game theory.  Saying that Charlotte Lucas accepts Mr. Collins’s proposal because of her need for financial security and not because of her personal preferences, as the letter does, relies on a quite narrow conception of preferences.  A person who does not read my book and holds this narrower conception would misunderstand my meaning.

To take another example, the letter states that “reducing autism to a few habits or character traits and conflating autism with cluelessness seems insulting and ignorant.”  A person who reads beyond the first chapter of my book can find that I quite clearly criticize people who have used the term “autistic” as a kind of disparagement.  I argue that mathematical social science should embrace its “autisticness,” which gives it a distinctive perspective.  A person who reads my book would discover that Phyllis Ferguson Bottomer, in her book So Odd a Mixture: Along the Autistic Spectrum in Pride and Prejudice, used the perspective of autism to look at Austen’s novels well before I did.  Of course my book does not attempt to reduce autism to anything.  The introductory chapter of a book does reduce the book’s arguments, by definition, but that is why the rest of the book comes soon afterward.

The problem of not reading, both your books and my own, is easily remedied by reading them.  Any problem which can be fixed by reading is a good problem to have.  It is an honor to be able to write to you, especially under the auspices of Scientific American.  Reading Scientific American as a child was my first introduction to the norms of scholarly communication.  Martin Gardner and C. L. Stong were childhood heroes of mine, and it is an honor to speak their names.

Respectfully yours,
Michael Chwe

(Credit: University of Texas, via Wikimedia Commons)

Dear Mr. Michael Chwe,

It is with a mix of delight, embarrassment and confusion that I have watched people analyze and adapt my novels all these years. Cassandra often hears of the latest developments before I do and takes great pleasure in bringing me tidbits of gossip. When she floats towards me with more enthusiasm than usual, I know she has information of a most scandalous nature to share: zombies, Jane, zombies! I have peered through the clouds at camera crews descending on the English countryside, the latest impersonation of my Lizzy in tow. I have eavesdropped on grad students presenting dissertations about the subtext of neocolonialism in my writing.  So far, I have been content to simply observe all this from my perch in the firmament—to rest my pen, if not my tongue. Now, however, immense gratitude and bliss compel me to write to you.

In naming me a game theorist, dear Sir, you bestow upon me more honor than I deserve. It is astonishing to me that, although I had no knowledge of game theory when I was writing my novels—and even though the field did not exist at the time—I “systematically explored the core ideas of game theory” in my work, as you confidently put it [PDF]. Some people may pounce upon such an assertion as anachronistic, but you convincingly argue that my novels are forerunners of a 20th-century academic discipline.

Only a man of your unparalleled perspicacity would realize that, “when you think about it, people have been thinking about strategic action for a long time,”—for far longer than game theory has officially existed. Indeed, if a strategy is a series of planned actions meant to achieve a specific goal, then my novels are full of strategy. Many of my characters scheme, manipulate and meddle. Of course, I would humbly point out that I was by no means the only or the first writer to notice that people strategize and manipulate one another to get what they want—and I certainly did not come up with the kind of mathematical models of decision-making central to game theory—but I think your notion of me as a game theorist remains impervious nonetheless.

When I invented the word ‘imaginist’ to describe some of my heroines, I hoped to convey their penchant for speculation and flights of fancy and their tendency to remake the world around them inside their minds—which often results in great disappointment. You clarify that what I really meant by ‘imaginist’ was “a theoretician of strategic thinking.” This is much more apt. And when I wrote of my characters’ penetrating minds and foresight—or lack thereof—I thought I was writing about the ability to look beyond one’s immediate circumstances. As you so graciously explain, however, “penetration” and “foresight” were actually my names for strategic thinking! That my novels catalogue “more than fifty strategic manipulations specifically called ‘schemes’” is not only a welcome surprise, but also further evidence of people’s inexhaustible talent for finding meaning in a writer’s sentences that she never intended herself.

“Austen starts with the basic concepts of choice (a person does what she does because she chooses to),” you write, “and preferences (a person chooses according to her preferences).” I feel as though you have reached into my brain and plucked out my thoughts. I firmly believe that every decision a person makes is based on his or her personal preferences. In Persuasion, Anne Elliot breaks her engagement to Frederick Wentworth because that was her preference, not that of her relatives. Likewise, in Pride and Prejudice Charlotte Lucas marries the unctuous Mr. Collins because she prefers him as a husband to anyone else in the world and not for any reasons related to her family or finances.

You are perhaps most discerning with regard to emotion and intimacy in my novels. “Austen’s heroines make good choices even when overpowered by emotion,” you write, concisely and accurately. This is exactly why Marianne Dashwood—all of 16 years and inundated with affection for John Willoughby—showers him with attention in public, sneaks off to his aunt’s house without a chaperone, and writes him a series of incredibly personal letters, even though they are not engaged and only recently acquainted. When Willoughby’s avarice and salacious past are revealed—when he abruptly severs all communication with Marianne and snubs her at a ball—she can be proud of her good choices and strategic thinking.

Finally, I am obliged to comment on what you deem “cluelessness, the conspicuous absence of strategic thinking” in my novels. The characters that you single out as clueless ostensibly “focus on numbers, visual detail, decontextualized literal meaning, and social status,” you write. “These traits are commonly shared by people on the autistic spectrum; thus Austen suggests an explanation for cluelessness based on individual personality traits. Another of Austen’s explanations for cluelessness is that not having to take another person’s perspective is a mark of social superiority over that person.”

Sir, I do not merit attribution for these ideas; they are entirely your own. I am not capable of such acute analysis. In my view, all my characters are necessarily concerned with social status as it influences everything they do. And, to me, reducing autism to a few habits or character traits and conflating autism with cluelessness seems insulting and ignorant. Some of my characters obsess over their clothes, physical appearance, money and social status not because they are incapable of strategic thinking, but because they are materialistic, selfish and narrow-minded people. In my books, people of all social ranks have difficulty adopting others’ perspectives. Lady Catherine de Bourgh may not deign to consider Elizabeth’s interests, but Lizzy fails to see Mr. Darcy’s point of view until she reads and rereads his letter and accepts that she had misjudged him. And some of my most intelligent and tactical characters (Emma comes to mind) make the worst blunders. But I have gone on too long about my own work and risk earning the label of narcissist in addition to game theorist.

So I thank you Sir and thank you again. I believe you have conceived a whole new way of looking at my writing, one that has yielded revelations never before articulated. I am exceedingly and selfishly glad that readers who can match your cleverness are rare in number, otherwise I fear people would spend more time reading books about my books than reading my novels themselves.

Most sincerely and affectionately,

Jane Austen

Dear Evolution,

Let’s start with the wings: did you really have to turn them into flippers? Don’t get us wrong—we appreciate the swimming and diving talents. But couldn’t you have come up with some kind of compromise so that we could still fly? Maybe a 2-in-1 special, a wing/flipper hybrid? After all, there are fish that can fly. Some squid can fly. And they don’t even have feathers. We know we’re not alone in being flightless, but you made ostriches, emus and cassowaries total badasses, what with their powerful legs and deadly claws. We’re more like large tuxedoed kiwis.

At least kiwis get to roam lush New Zealand. We’re stuck on the coldest, driest, windiest continent on the planet. We live in Earth’s deep freezer—way at the back, with the pack of peas encrusted in ice. Speaking of ice, where are our retractable keratin crampons? That doesn’t seem like a particularly complicated adaptation. You showed a lot of foresight with snowshoe hares and you found the time to decorate gecko feet with bazillions of sticky microhairs. Can we get a little traction too? We’re pretty good at waddling, but we still slip and fall over—a lot.

Finally, there’s the matter of our voices. There seems to be something of a musical imbalance in the bird world. Thrushes, finches, warblers, Lyrebirds and the like—you gave them all your acoustic gifts. What about the rest of us? Considering that we live somewhere so barren—where the only ambient sounds are calving glaciers, furious frigid gusts and the creepy distended whistles of Weddell seals—it would be really nice to entertain ourselves with some songs. Unfortunately, our best attempts at melody sound like a car struggling to start.

We may live at the bottom of the world but we think it’s time you moved us to the top of your priority list.

Sincerely,
Emperor Penguins

Dear Evolution,

Seriously?

No love,
Giraffe

Dear Evolution,

Send help. Soon.

Desperately,
Angora Rabbit

Dear Evolution,

It’s rather odd, you know. Considering how important reproduction is to your whole raison d’être and whatnot, one would think that you’d make it as pleasant as possible. And yet so often it’s such a ghastly affair. All that belly-swelling and nutrient-sharing and hatching through odd orifices—I dare say it’s all most undignified.

So I find it quite delightful that when it came time to delegate within my species, you placed the burden of childbirth on the fairer sex—by which, of course, I mean the males. It’s just such a relief not to be troubled with it. All I have to do is perform a lovely mating dance and then inject him with my ovipositor; then he’s the one who carries the precious little parasites around and forcibly expels them from his abdomen when the time comes. It’s no fuss for me at all. I don’t know why the females of other species put up with all that nonsense, honestly.

It was just so terribly thoughtful of you. And this way I have much more time to party.

With undying gratitude,
Lady Seahorse

Dear Evolution,

How you doin’?

Birds of Paradise

This post was brought to you by Mara Grunbaum, creator of WTF, Evolution?, and Ferris Jabr, associate editor at Scientific American.

Image Credits:

Giraffe: cjuneja, via Flickr

Angora rabbit: Betty Chu, via Wikimedia Commons

Seahorse: Nick Hobgood, via Wikimedia Commons

TRANSCRIPT

After Thanksgiving dinner, many people start to feel a little drowsy. Turkey typically gets the blame. It supposedly contains high levels of tryptophan, an amino acid that is sold in a purified form to help people fall asleep.

But turkey contains about the same amount of tryptophan as chicken, beef and other meats.

If Thanksgiving drowsiness is not about the main course, what is responsible? It may have more to do with the side dishes.

To understand, we first need to digest a little food chemistry.

To start, we get tryptophan and other essential amino acids from all the protein in our diet, not just from meat. These amino acids swim through the bloodstream, nourishing our cells.

Brain cells convert tryptophan into a chemical called serotonin. This neurotransmitter helps regulate sleep and appetite and high levels of serotonin are associated with calm and relaxation.

But tryptophan and other amino acids can’t access brain cells on their own—instead, teams of proteins transport amino acids across the blood-brain barrier.

As it turns out, Thanksgiving side dishes probably make it easier for tryptophan to get inside the brain.

Mashed potatoes, stuffing and bread—as well as dessert—contain a lot of carbohydrates, which stimulate release of the hormone insulin.

Insulin encourages our muscles to absorb certain amino acids from the blood—but not tryptophan. So eating all those carb-heavy side dishes increases the amount of tryptophan in the blood relative to other amino acids, which means more tryptophan gets into the brain.

This eventually translates to higher serotonin levels, which probably contribute to Thanksgiving stupor.

However, this complex chain of chemical reactions is not the only reason people feel sleepy on Turkey Day

Studies have confirmed big meals of any kind make people drowsy. It takes a lot of energy to digest all that food. Also, during festive meals, many people enjoy a little beer or wine, making slumber all the more appealing

And on top of it all, preparing such a large meal is physically exhausting, not to mention all the arguing—I mean, socializing—with extended family.

For Scientific American’s Instant Egghead, I’m Ferris Jabr.

References

Anita S. Wells, Nicholas W. Read, Chris Idzikowsk, and Jane Jones. Effects of meals on objective and subjective measures of daytime sleepiness. Journal of Applied Physiology. February 1, 1998 vol. 84 no. 2 507-515

Høost U, Kelbaek H, Rasmusen H, Court-Payen M, Christensen NJ, Pedersen-Bjergaard U, Lorenzen T. Haemodynamic effects of eating: the role of meal composition. Clin Sci (Lond). 1996 Apr;90(4):269-76.

Eating Turkey Does Not Really Make You Sleepy by Jason Kane, PBS Newshour

Myths about myths about Thanksgiving turkey making you sleepy by Bora Zivkovic, A Blog Around The Clock

Self Nutrition Data: Foods highest in tryptophan

Interviews with Dr. Richard Wurtman and Dr. Judith Wurtman

Over the years, Iceland’s unique geology and diverse landscapes have appeared in Björk’s art in one way or another. In one of her most recent songs, “Mutual Core,” Björk uses geological activity as a metaphor for the volatility of an intimate relationship—a metaphor for intimacy’s friction, conflicts and rifts, as well as its seemingly unbreakable bonds forged in fiery passion; for the attempt to rearrange parts of oneself to better fit another; and for periods of relative calm punctuated by eruptions of emotion. The music video for “Mutual Core,” released this week, is a gorgeous, explosive and sensual imagining of tectonic movements.

Björk and her team chose Los Angeles-based filmmaker Andrew Thomas Huang to direct the music video for “Mutual Core.” Huang wrote the initial treatment for the video in London, where he visited geological museums for inspiration, studying the color palettes of rock collections and watching videos of magma ballooning from underwater volcanoes.

The video opens with crumbling layers of earth, reminiscent of sand art. Björk, wearing a blue wig, golden dress and a brooch she designed herself, stands in the middle of a sandpit, a piece of rock in each hand—chunks of lava rock that Huang’s crew collected on location in Iceland. Huang and his team gathered the sand from local mining sites: “In Iceland they have black sand everywhere,” Huang explains, “but we went searching for warm orangey beach sand that we thought would be more appropriate.”

Björk waves the pieces of lava rock over the sand, which shifts as though concealed dolphins are swimming through the grains. She buries the rocks, which emerge as larger floating boulders flickering tongues of overlapping turquoise, pink and yellow stone. The hovering rocks are puppets made from foam and covered in plaster, fossilized barnacles and various decorative textiles; the tongues are all computer animation. “I like using practical effects and puppetry as much as I can,” Huang says. “If it’s too digital, it feels dead. Björk and I were examining not just the act of tectonic subduction [when one plate moves beneath another], but also how it’s represented in science education. We always see strata [layers of sediment] laid out as colorful graphic ribbons. That was the impetus for the rainbow colors cascading over each other.”

The floating rock puppets embrace in a kind of kiss, their tongues pushing against one another like tectonic plates, so that one dives beneath the other. They separate and more rocks rise from the sand, somersaulting in circles around Björk. Most of these rocks are computer animations. “We had to calculate how millions of sand particles would cascade over rocks, which is an incredibly challenging thing to animate” Huang says. “Our technical director spent two months developing a system for rocks to kick up sand.”

Björk’s face appears in the rocks’ colorful tongues as they merge once again, this time more violently, bursting into flame, spitting magma and growing into a volcano that spews molten lava as the song reaches its first climax. In the next scene, Björk dances in the sand pit beneath a soft shower of ash and the rock puppets reappear with more fully formed Björk faces in their strata. They meld violently once more, forming a “mutual core” and morphing into an even larger volcano flanked by two Björk boulders sitting back to back, like a statue of Janus, the two-faced Roman god of doorways and transitions. “For this scene, we filmed Björk in gray makeup with pebbles stuck to her face for texture and tracked the motion of her face in CG. She also wore a headdress made by an artist with crystals and gems,” Huang says. “The rest of her costume is graphics. We wanted her to look like an Earth goddess. We were looking at a lot of Thai and Indonesian costumes and statues.”

In some scenes, Björk appears to spit magma from her mouth. In reality she was spitting out a mixture of ketchup and cake batter, which was later modified to look like red-hot lava. “Magma has a certain consistency, the way it flies and explodes. The crew experimented with various materials and decided cake batter and ketchup was the best way to do it,” Huang says. The crew also shot plates of the gooey combination from an air compressor and filmed the resulting splats and splutters in slow motion.

“Mutual Core” belongs to the album Biophilia, Björk’s most overt celebration of science, human biology and the natural world: song titles include “Virus” and “Dark Matter.” But this is not the first time that nature and science have featured prominently in Björk’s work. In “Joga,” Björk sings of “emotional landscapes” and the accompanying music video, directed by Michel Gondry, takes us on a breathtaking aerial tour of Iceland. Computer animation splits the country’s crust to reveal magma beneath. In “Oceania,” Björk sings from the perspective of the ocean, in whose waters all life began: “Your sweat is salty / I am why.”

“You might think, Who would ever make a song about tectonic plates?” Huang says, “But one of the things that makes Björk so genius is that she is one of very few artists who attempt to make poetry from science plus music. Typically we associate volcanic activity with anger or ferocity. Björk gets happy when she thinks of a volcano; she thinks it can be positive too. That’s something I hope came through in the video.”

("A Perch of Birds," by Hector Giacomelli, via Wikimedia Commons)

My father called me one night: “So, I’m trying to figure this thing out. How does it work exactly?” Some of my friends and colleagues have made similar inquiries: “I should probably get the hang of this. Can you show me?”

The thing, the ‘this’ in question, is Twitter.

Type “What is t—” into Google’s search bar and its autocomplete feature suggests “What is twitter” right away. Type “How to use—” and “How to use twitter” pops up.

I am not, nor will I ever claim to be, a social media expert. But I’d like to share one way of thinking about Twitter that I have found helpful.

Twitter is like a 24-hour party. Everyone is invited. And you can come and go as you please.

More than 140 million people currently attend this party. Everyone wears a nametag, which usually includes a few descriptive sentences —a ‘bio’—and may identify where someone lives.

Upon first joining the Twitter party, most people associate with those they already know. Perhaps more than any other party in history, however, Twitter offers the opportunity to make new friends—to meet people whom one might not have met otherwise. Unlike a typical party, occupying the same physical space is not a prerequisite to meaningful interaction on Twitter. Geography and time zones become less problematic than usual. And because there are so many people at this party, the chances of finding someone with whom you share common interests are pretty high.

If you want to hear what someone is saying at a typical party (without eavesdropping or being creepy), you have to introduce yourself. On Twitter, all you have to do is press the “Follow” button. In most cases, no one has to approve the request. You push the button and that’s it—you are instantly privy to just about everything that person says out loud, everything they “Tweet.” That’s what tweeting is, really—it’s just another way of talking.

You could leave it at that: just listen in on other people’s conversations, never saying much yourself. But if you really want to meet people and make new friends, you’ve got to do what you would do at a typical party: introduce yourself to strangers. You’ll have to risk awkwardness and rejection. At a standard party, you might sidle up to some people you don’t know, asking to join their conversation with your body language and a brief greeting. On Twitter, you use the versatile @ symbol. Depending on how you use it, it’s the equivalent of calling someone’s name, tapping them on the shoulder, meeting their eyes, speaking directly to them or waving frantically from across the room like an ardent fan who just spotted the Biebs. Some people might not pay attention to you when you first reach out. That’s to be expected. Most relationships—whether online or IRL—take time. And that’s what Twitter is all about: relationships, conversations, community. Some people make a Twitter account, send a few tweets addressed to no one in particular and wonder why they do not have many followers. Well, that would be the equivalent of going to a party, standing in the middle of the room and spouting random one-liners now and then.

Critics and curmudgeons often dismiss Twitter as an incessant stream of the trivial falling off the edge of the Internet into a vacuum:

@sallyinyerface86 Just had pancakes YUMMY!!

@markaroniandcheese773 Dude. The sky. Is. So. Blue.

Yes, as with many parties, certain guests will have a penchant for the mundane, the ludicrous and the offensive. But that does not describe everyone. And, just like at a typical party, no one is obligated to pay attention to people they find boring or rude. In some ways, it’s far easier to ignore people you do not particularly like on Twitter than at a typical party. You can ‘Unfollow’ someone with the click of a button, temporarily mute that person or even prevent him or her from ever contacting you again.

Twitter also makes it easier to find people who are talking about things you’re interested in. At a standard party, you might catch a snippet of intriguing dialogue from afar. On Twitter you can search for conversations that might interest you by using hashtags—phrases prefixed with the # sign. If you want to talk to others about penguins, search for #penguins; if you see someone tweeting with an #election hashtag, click on it to find related tweets. If you want other people to find your tweets about gardening, label them #gardening. Hashtags have also become a tool for irony, sarcasm and humor. When talking with someone in person, you can change the tone, pitch and cadence of your speech—as well as your entire countenance—to convey your attitude about a subject; on Twitter, you have to get crafty with letters, punctuation and other symbols. A hashtag can be the virtual equivalent of arching your eyebrows or saying something in a funny voice: @LizLemonFan654 I’m so excited to stay in this weekend!! Lifetime movie marathon and microwavable dinners, here I come! #iwillprobablydiealone

If someone on Twitter says something you really like, you can ‘Retweet’ what that person said—it’s kind of like getting your friend’s attention in order to share a funny story or interesting fact you just learned. Twitter makes it all the easier to indulge the inclination to share: you can instantaneously broadcast what someone said, word for word, to all of your followers. You don’t have to say everything aloud, though. At a typical party you might whisper something in someone’s ear or find a quiet corner to talk alone; on Twitter you can send a ‘Direct Message’—a private correspondence.

A bird’s eye view of a typical party would reveal many circles smushed together—little pods of people conversing. Twitter is similar. Each person on Twitter is part of a unique circle comprised of people they follow and people who follow them. All these circles overlap, like ripples on the surface of a pond. At a standard party, you don’t have to talk to the same people the whole time—you can move from one pod to another. On Twitter, you are even more mobile. Your tweets can zip around the orbits of many different social circles simultaneously. You can expand the circumference of your unique circle over time. You are constantly free to find and join new circles. And you have the power to bring rather dissimilar circles nearer one another.

Over time, these circles become genuine communities. You get to know the people who have chosen to follow you and the people you follow get to know you. You have real conversations with them. You come to depend on one another for news and advice, for sympathy and laughs, for gossip, commiseration and comradery. Perhaps you even meet some of these new friends in person, further strengthening your relationships.

At a typical party, even if you hit it off with someone—even if you exchange numbers—you will both have to make the effort to see each other again if there’s any hope of a friendship. And, let’s face it, making effort is hard. Twitter helps here too. As long as you continue to follow someone, and they continue to follow you, Twitter will make some of the effort on your behalf, ensuring that you “see” each other on a regular basis. A single typical party usually offers fleeting moments of intimacy. Because Twitter is a nonstop party, it gives you all the time you need to build something more substantial.

Oh, and it’s BYOB.

(Credit: adapted from image by John A Beal via Wikimedia Commons)

Scientists have mapped, charted, modeled and visualized the human brain in many different ways. They have marked the boundaries of the organ’s four major lobes: the frontal, parietal, temporal and occipital lobes. They have divvied up the cortex into more than 50 Brodmann areas—small regions characterized by particular cell types and specific cognitive functions, such as processing speech and recognizing faces. Researchers have tagged individual neurons with fluorescent proteins, transforming gray tissue into stunning brainbows, and followed water molecules as they move through the nervous system to trace ribbons of neural tissue linking one brain region to another. More recently, some scientists have championed the importance of connectomes—detailed wiring diagrams of all the connections between neurons in a given nervous system or brain. Thoroughly understanding the brain, proponents of connectomics argue, requires precise maps of its neural circuits.

The standard way of making a connectome is serial electron microscopy—chopping up an animal’s brain into thin sheets, taking photos of all the resident neurons through an electron microscope and using those photos to painstakingly reconstruct the connections between neurons. In the 1970s biologist Sydney Brenner and his colleagues began using this technique to map the 302 neurons and 7,000 neural connections, or synapses, in the nervous system of a tiny worm known as Caenorhabditis elegans. It took them more than 12 years to finish the map. So far, C. elegans is the only animal with such a thorough connectome. Since mammalian brains contain millions or billions of neurons and billions or trillions of synapses, depending on the species, researchers are searching for faster and cheaper ways to create connectomes. At Harvard University, for example, Jeff Lichtman and his colleagues have constructed an Automatic Tape-Collecting Lathe Ultramicrotome (ATLUM)—a machine that speeds up the business of slicing up brain tissue into thin sheets with conveyor-belt efficiency.

One way to map the brain: Neuroimaging data, combined with computational analyses, reveal highly connected, centrally located regions of the human cortex (Credit: Liza Gross, via Wikimedia Commons)

In a new essay, Anthony Zador of Cold Spring Harbor Laboratory has outlined what could be the fastest and cheapest way to construct a connectome yet—if he and his teammates surmount some significant hurdles. Their strategy, which is still in the proof of principle stage in the lab, depends on DNA barcodes and a virus that has evolved to evade the immune system by sneaking through neural highways. Zador and his colleagues call their method BOINC (Barcoding Of Individual Neuronal Connections).

The basic idea behind BOINC is to take advantage of increasingly swift and inexpensive DNA sequencing technology to make connectomes. What if instead of reconstructing the connections between neurons with thousands of digital photographs, one could instead infer how neurons are connected by analyzing their DNA? Here’s how it might work.

The first step in BOINC is assigning each and every neuron in a brain a unique DNA barcode—a distinctive sequence of DNA’s nucleotide building blocks, A, T, C and G. To accomplish this, Zador proposes shuffling a specific segment of the neurons’ genomes with enzymes called recombinases that specialize in such genetic scrambling. If the segment of DNA is long enough, and the researchers use enough recombinases, the chance that any two neurons would end up with the same reshuffled sequence would be quite low, Zador says. He calculates that the possible permutations of a 20-nucleotide barcode could uniquely label the approximately 70 to 100 million neurons in an entire mouse brain. Once the neurons have been labeled, a different team of enzymes would excise the barcodes from the neurons’ genomes and package them into plasmids—circular loops of DNA.

Analyzing the DNA at this stage would reveal nothing about the connections between neurons because the free-floating DNA barcodes would still be confined to their respective cells. What is needed is a way for connected neurons to exchange copies of these DNA barcodes. Enter the pseudorabies virus (PRV), which is actually much more closely related to the herpes virus than the rabies virus. PRV mostly infects pigs—although many other mammals are susceptible—causing fever, sneezing, coughing, constipation and severe itching. The virus hides from the immune system by crawling through neurons’ interconnected branches toward the brain, hopping across synapses—the tiny gaps that separate communicating neurons.

For several decades now, scientists have tracked PRV as it moves through a nervous system in order to trace the connections between neurons. Zador proposes something entirely new: coaxing PRV to endow DNA barcodes with the properties of a functional virus, so that they too can travel from one neuron to another.

When PRV enters a cell, it brings an entourage of proteins that get right to work hijacking the cell’s molecular machinery and making many copies of the PRV virus. This whole process kicks off when the ensemble of viral proteins recognize and bind to specific sequences of DNA in the virus’s own genome. By weaving these genetic sequences into the free-floating plasmid DNA barcodes, Zador and his team trick the PRV’s helper proteins into giving these barcodes the protein sheath that allows PRV to hop from its host cell to a connected neuron. Essentially, the DNA barcodes become viruses in their own right. Importantly, Zador must ensure that these viral DNA barcodes have one-way, single-ride tickets—that they make one hop and then stop. He thinks he can terminate a barcode’s journey after one hop by restricting access to an enzyme that helps it travel across synapses.

If all goes well, the neurons become “bags of barcodes” as Zador puts it—but not grab bags of barcodes from all over the brain. Rather, since the DNA barcodes only made one hop, each neuron should have copies of its own unique barcode as well as copies of barcodes from all the neurons to which it is immediately connected, but not from any other neurons. Within each neuron, yet another enzyme named phiC31 integrase would join the barcodes from connected neurons into pairs. Each neuron would then have as many barcode pairs as it has connections to other neurons. Finally, the researchers would grind up the brain tissue, extract the DNA and make many copies of all the paired DNA barcodes, which would allow them to infer the connections between neurons. If Alpha34X’s unique barcode is paired with the barcodes of Omega16P, Gamma78V and Delta23W, then those cells must be immediately connected. Zador’s essay appears online October 23 in PLoS Biology.

BOINC is a series of complex steps involving subtle genetic and molecular manipulation—a lot can go wrong along the way. Although Zador has by no means overcome the many technical challenges that BOINC poses, he has been encouraged by promising first-attempts and hopes to publish experimental results soon. “We have all the steps working by themselves and proof of principle where they are all working together fairly well,” he says. So far, he and his colleagues have focused on cultures of mouse brain cells and have been able to deduce a neural circuit comprised of a couple hundred neurons from DNA analysis, although they do not yet know how closely it matches the anatomical circuit in the mouse brain. Zador estimates that it would cost about $48,000 and one week of work to eventually “sequence the connectome” of a whole mouse brain.

“Without a really good hypothesis about underlying neural circuitry, you can blow a couple years of research,” Zador says. “With a connectome, we can generate hypotheses and ask, ‘Does this even make sense?’ We can look at the map and say, ‘Oh, nope, couldn’t be that way.’ We constrain our hypotheses tremendously if we know what the wiring diagram is. I don’t expect that understanding the connectome will give us all the answers to how the brain works, but what I expect is that it will completely change how we look for answers.”

One type of midshipman fish, the Atlantic midshipman (Porichthys plectrodo). Note the photophores along its belly. (Credit: SEFSC Pascagoula Laboratory; Collection of Brandi Noble, NOAA/NMFS/SEFSC, via Wikimedia Commons)

With the exception of the cast of Disney’s The Little Mermaid—and Big Mouth Billy Bass—fish do not spring to mind as the animal kingdom’s most vocally gifted members. But one unusual singing fish has been teaching biologists and neuroscientists a lot about speech and hearing. Its bulging eyes and blubbery lips have graced several research posters at the Society for Neuroscience’s annual meeting, which is in New Orleans, Louisiana this year.

The finned crooner in question is the plainfin midshipman fish (Porichthys notatus), which belongs to a family of fish known as toadfish because of their squat, slimy appearance. Midshipman fish live along the Pacific coast from Alaska to Baja California at depths of up to 300 meters, burying themselves in the mud during the day and surfacing at night to feed. Their name is attributable to the hundreds of luminous spots called photophores that decorate their underbellies, which are somewhat reminiscent of the buttons on a naval officer’s uniform. The fish likely use these bioluminescent dots to attract small prey such as krill and to hide from predators by masking their own shadows with a camouflage technique known as counter-illumination.

Midshipman fish come in three varieties: females, Type I males and the smaller Type II males. All three types are vocal, emitting short grunts to communicate with one another, but Type 1 males are the most voluble by far. In the spring and summer, Type 1 males head to shallow waters, excavate nests beneath rocks along the shoreline, hunker down and start to sing, using sonic muscles surrounding their inflatable swim bladders to hum for up to an hour at a time. This humming, which people have described a droning motorboat or an orchestra of mournful oboes, is so loud that it has been known to wake houseboat owners in San Francisco and Sausalito (Listen to a clip of the humming here). Female midshipman fish follow the singing to the Type 1 males’ nests, where they lay their eggs. Type II males are little sneaks. They also listen for the calls of Type I males and look similar enough to females to slip past a Type 1 male and fertilize any recently laid eggs in his nest before the Type 1 male gets a chance to release enough of his own sperm.

Credit: Original Illustration by Nicolle Rager Fuller, National Science Foundation

Studying how midshipman fish call and respond to one another has taught scientists about the evolution of vocal communication and the neurobiology of hearing. In one study, Andrew Bass of Cornell University traced the development of the midshipman fish nervous system and brain, focusing on neurons that control their sonic muscles. The fundamental structure of the brain circuit he traced was remarkably similar to neural circuits in corresponding brain regions in amphibians, birds and mammals. Because toadfish first evolved so long ago, Bass concluded that this particular neural circuit is likely 400 million years old—almost as old as vertebrates themselves. Of course, different groups of animals have tinkered with this basic neural archetype over the course of evolution—and developed very different systems of muscles and tissues for vocal communication—but nonetheless our own speech and song owe a lot to the ancient grunts and hums of midshipman fish. In more recent work, Bass has continued to explore the underwater origins of vocal communication, as well as whether fish were the first animals to evolve some common non-vocal gestures.

Bass and his colleagues have also discovered that Type 1 male midshipman fish deliberately desensitize their ears to sound when they are humming to avoid damaging their ear hair cells. At the same time that a male midshipman fish’s brain stimulates muscles surrounding the swim bladder, it sends electrochemical messages to ear hair cells, essentially telling them to put in earplugs. These two types of signals happen in sync about 100 times every second. Since all vertebrate brains have similar living links to the ears, Bass and his colleagues propose that four-limbed animals like echolocating bats, barking dogs and human pop stars might rely on related acoustic strategies to protect and preserve their hearing when they are making loud sounds.

Now, Elizabeth Whitchurch, currently at Humboldt State University, and her colleagues have shown that Type 1 males have bigger distances between their swim bladders and their ears than Type II males and females. This adaptation may further help Type I males protect their hearing during the mating season. Whitchurch presented her findings at the Society for Neuroscience’s annual meeting.

In related research, Joseph Sisneros of the University of Washington and his colleagues have established that as the breeding season approaches, sex hormones flood the bloodstreams of midshipman fish, which in turn changes their singing and hearing. Female midshipman fish are most attuned to the males’ mating calls when their estrogen levels are high. Similarly, the most successful male baritones have the highest levels of testosterone. In addition to teaching researchers how hormones modulate the nervous system, studying these changes could help scientists understand whether people’s hearing declines as they get older in part because of waning hormone levels. In some studies, mice deficient in estrogen or estrogen receptors suffer faster and more severe hearing loss and scientists have proposed that hormone therapies could stave off age-related hearing loss in women.

When it comes to animal research on speech, music and hearing, songbirds like zebrafinches and squeaking mice usually get the spotlight. Who would have thought that a humble mud-dwelling toadfish would give scientists so much to say about vocal communication? In honor of this unlikely inspiration, let’s make some noise: three cheers—or grunts—for the plainfin midshipman fish!

Spiny mice at the Louisville Zoo (Credit: Ltshears, via Wikimedia Commons)

Many species of starfish relish oysters, clams and other shellfish, much to the chagrin of fishermen who watch over oyster beds and farms. Legend has it that oyster fishermen used to dispose of any starfish they dredged up by cutting the creatures in half and tossing them back into the ocean. Since starfish can regenerate lost limbs, the fishermen unwittingly doubled their foes’ numbers. It’s hard to say exactly how true this oft-repeated story is, but starfish’s regenerative talents are biological fact. Salamanders, newts and many other amphibians can regrow severed limbs too, replacing all the missing bone, muscle, nerves and skin without any trace of scar tissue. By and large, mammals are not so fortunate. Perhaps the most notable exception is a particular strain of lab mouse known as Murphy Roths Large (MRL), which seals small holes in its ears and regrows toetips thanks to its unique gene expression.

Now, scientists have confirmed that at least two species of wild mice in Africa can swiftly regenerate missing skin, hair follicles, fat cells and cartilage much like salamanders and newts. The new study—coupled with research on MRL mice—suggests that tissue regeneration may not be as uncommon in mammals as once thought and that the mammalian genome conceals a latent ability to regrow damaged body parts.

In discussions with ecologists, biologist Ashley Seifert of the University of Florida learned that African spiny mice frequently lose their tails—in the same way a salamander’s tail might detach in the mouth of a hungry bird—and that large chunks of the rodents’ skin easily slough off their bodies, possibly as a related defense against predators. Seifert wondered, though, how any mammal could manage to lose so much skin and still survive. Surely the animal would have to grow most of that skin back.

A few months later, Seifert traveled to Kenya and began trapping spiny mice (particularly Acomys kempi and Acomys percivali) in the rocky hills where the rodents live. Every time one of the captured spiny mice struggled in his grasp, its skin peeled off. In mechanical tests, Seifert discovered that it takes nearly 77 times more energy to break typical mouse skin than to tear African spiny mouse skin. On a cellular level, typical mouse skin and African spiny mouse skin look more or less the same. However, spiny mice have far larger hair follicles than typical mice. The follicles take up so much room, Seifert and his colleagues reason, that spiny mouse skin has much less connective tissue holding it together than typical mouse skin, making it more fragile.

When Seifert and his colleagues gave the spiny mice a few nicks, bleeding promptly stopped and scabs formed rapidly. The mice grew new skin over their wounds within 3 days; adult rats take between 5 to 7 days to do the same. 10 days after injury, the spiny mice’s skin had healed without much scarring. Instead of arranging new collagen fibers in the tough, dense networks typical of scars, the spiny mice’s new collagen scaffolding was similar to that in healthy skin. By day 21, the spiny mice were growing brand new hairs to replace the ones they had lost.

Unwounded spiny mice (top row); with large open wounds (middle); and after 30 days of healing. (Credit: Ashley Seifert et al, Nature)

Even more impressive was the mice’s ability to heal 4 millimeter holes in their ears: they quickly closed the holes with new skin, regenerating hairs, fat cells and cartilage—but not muscle—without any scar tissue. In contrast, typical mice that Seifert tested failed to seal the wounds in their ears, forming scars instead. The results were published in Nature (Scientific American is a part of Nature Publishing Group).

When salamanders and newts regenerate an entire limb—a process known as epimorphic regeneration—one of the first steps is the formation of a blastema, a mass of cells that revert to an immature, undifferentiated state so that they are versatile enough to become the many different kinds of tissues in the new limb. Seifert observed clumps of unspecialized cells surrounding the spiny mice’s ear wounds that looked very much like genuine blastemas: “Having done plenty of work on salamanders and such, what I saw in the mice looked almost identical. My colleagues and I were saying, ‘This looks like a mammalian blastema!’ You could see a conveyor belt of new hair follicles growing in the ear and undifferentiated cells—all the hallmarks of regeneration seemed to be there.” In future work, Seiffert wants to examine these cells in more detail to confirm their true identity.

In past studies, scientists discovered that part of the reason Murphy Roths Large mice can regenerate ear tissue is not that they have a mutant gene or an additional gene, but rather that they do not express a particular gene known as p21. In related research, scientists reverted mouse muscles cells to a blastema-like state of immaturity by temporarily knocking out two tumor-suppressing genes. Extending the logic of these findings, p21 and other genes may suppress latent regenerative abilities in typical mice and indeed in most mammals. Learning to precisely control these genes at will opens the prospect of healing injuries in people by restoring our lost power of tissue regeneration. African spiny mice now offer scientists new opportunities to investigate such possibilities.

A section of healthy brain tissues contrasted with brain tissue from someone who had advanced Alzheimer's disease. (Credit: National Institutes of Health, via Wikimedia Commons)

We all lose brain cells as we get older. In people with neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s, neurons shrivel and die at alarming rates—perhaps three to four times faster than usual in Alzheimer’s, for example. Currently, no known drugs reliably halt or reverse such staggering cell death in people, although some drugs are thought to protect neurons from degradation.

An alternative to saving dying neurons—or perhaps a future supplemental therapy—is creating brand new neurons. One way to accomplish this is transforming non-neuronal brain cells into functional neurons. On a cellular level, the brain is as diverse as a rainforest populated by many different species of trees. The human brain contains approximately 170 billion cells, 86 billion of which are neurons and 84 billion of which are glial cells—non-firing cells that assist neurons in various ways. Star-shaped cells known as astrocytes are perhaps the best-studied of the many various glial cells and researchers have had some success converting astroyctes into neurons. Many of these studies, however, have used cells from very young rodent brains.

A study published this week suggests that it’s possible to turn at least one class of adult human brain cells known as pericytes into functional neurons. The fact that pericytes help defend and heal the brain—and may retain some of the plasticity of stem cells—makes them all the more appealing as candidate replacements for damaged and dying neurons.

Benedikt Berninger of Ludwig-Maximilians University Munich and his colleagues began their research project with the intent to study astrocytes, just as they have done many times before. They acquired 30 samples of brain tissue from people who were undergoing surgery for disorders such as epilepsy. Sometimes, in order to remove or treat a damaged or malfunctioning brain region, neurosurgeons cannot avoid slicing through healthy brain tissue. Surgeons routinely provide sections of such healthy tissue to researchers studying the brain.

In the lab, Berninger and his teammates grew cultures of brain cells from the tissue samples and searched for astrocytes nestled among the tiny neural gardens. As it turned out, the cultures Berninger and his colleagues grew were mostly devoid of astrocytes. Instead, their Petri dish gardens were rife with pericytes—non-neuronal brain cells that wrap themselves around the brain’s delicate blood vessels, regulate blood flow to neurons and help maintain the blood-brain barrier, which protects neurons from bacteria and other pathogens. Pericytes are also known to proliferate in response to injury. Researchers recently showed, for example, that pericytes are essential for the formation of scar tissue in an injured spinal cord. Some evidence even suggests that certain kinds of pericytes boast the same flexibility as mesenchymal stem cells—they can turn into bone cells, fat cells or cartilage cells.  Perhaps, Berninger and his colleagues reasoned, the plasticity of pericytes—coupled with their role in healing—might make them especially useful in future treatments for neurodegenerative diseases. So they decided to try changing pericytes into neurons by reprogramming their genomes.

An astrocyte stained with green fluorescent proteins (Credit: Dantecat, via Wikimedia Commons)

Using viruses, Berninger and his team infected the pericytes in their cultures with two transcription factors—proteins that alter gene expression by binding to segments of DNA and making certain genes more or less accessible to other cellular machinery. One of the transcription factors, Mash1, is known to guide the development of the nervous system. We all begin life as a hollow ball of embryonic stem cells that eventually become the many different kinds of cells in the human body. All somatic cells in your body have the same DNA, but distinct types of cells express very different sets of genes—just as different piano songs are unique combinations of notes played on the exact same set of keys. MASH 1 is like a tiny composer inside embryonic stem cells, making sure they turn on the right combination of genes to become neurons. The second transcription factor Berninger and his colleagues introduced into pericytes was Sox2, which is highly active in stem cells and thought to make DNA more amenable to manipulation by loosening the chemical bonds between DNA and the protein scaffolding that keeps it tightly wound in a bundle called chromatin.

The scientists successfully converted between 10 and 30 percent of the pericytes in various cultures into neurons; the overall success rate was 19 percent. Out of 17 successfully converted neurons selected for further testing, 12 generated electrical impulses. Berninger and his colleagues replicated these results with brain cells from adult mice. The results appear in Cell Stem Cell.

Treating neurodegenerative diseases by genetically reprogramming brain cells is a potential avenue for therapy that researchers have just started to navigate—and they will have to scale plenty of hurdles along the way. Scientists must ensure that the viruses they use to ferry genes or transcription factors into brain cells are harmless.* And they would likely have to perform risky invasive surgery to get the viruses into exactly the right region of the brain. In recent years, however, gene therapy has safely restored vision to the blind. Not only do studies like Berninger’s suggest that gene therapy for the brain has similar potential, they also confirm that the fates of some adult cells are not written in stone—rather, they are written in highly editable DNA.

*Editor’s note: this sentence was edited for accuracy and clarity

Image via Wikimedia Commons, adapted from Christopher Walsh, Harvard Medical School, by Gary2863

In the September 17th issue of The New Yorker, Anthony Gottlieb analyzes Homo Mysterious: Evolutionary Puzzles of Human Nature, a new book by David Barash, a psychology professor at the University of Washington in Seattle. Gottlieb’s article is more than just a book review—it’s also the latest in a long line of critiques of evolutionary psychology, the study of the brain, mind and behavior in the context of evolution.

Gottlieb makes several excellent points, describing the same major shortcomings of evolutionary psychology that critics and proponents alike have named many times before: frustratingly scant evidence of early humans’ intellect, the immense difficulty of objectively testing hypotheses about how early humans behaved, the allure of convenient just-so stories to explain the origins of various mental quirks and talents. Some of his points are less relevant, such as psychologists’ oft-lamented dependence on American and European college students as study subjects—this is a problem for all of psychology, not just evolutionary psychology.

One of Gottlieb’s arguments stunned me—an argument so weak that it disintegrates when probed, like a flake of sandstone. “In theory, if you did manage to trace how the brain was shaped by natural selection, you might shed some light on how the mind works,” Gottlieb writes. “But you don’t have to know about the evolution of an organ in order to understand it.”

Yes, you do.

Gottlieb gives the example of English physician William Harvey, who “figured out how [the heart] works two centuries before natural selection was discovered.” As precise, detailed and beautiful as Harvey’s descriptions of the heart and circulatory system were, they did not explain the origins of the heart as a functional organ. Why do different animals have different kinds of hearts? Why do some animals have blood but no heart?  When, how and why did hearts arise in the first place? Simply knowing how the heart works is not sufficient to answer these important questions. Rather, one needs to understand how the heart evolved. Such understanding contributes to more than basic biology—it also advances medicine. Tracing how gene expression in heart cells has changed over evolutionary time, for example, has simultaneously improved our understanding of congenital heart defects.

Just as evolution shaped the human heart’s structure and function, evolution sculpted the human brain—as well as the mind. This is an inescapable fact. The brain and mind are inextricable. In order to understand one, you must understand the other. Changing a brain’s structure changes how that brain behaves and what kind of mind emerges from its interaction with the environment. We have clear evidence of this from people who have endured swift and dramatic changes to their brains through traumatic injury, stroke and neurodegenerative diseases like Alzheimer’s. Likewise, the more gradual structural changes to the human brain during the course of its evolution mirror an evolution of the human mind. Consciousness, self-awareness, complex emotions, language, creativity—if you want to truly understand these aspects of mind, you must understand when and why they first evolved. To do that, you must understand how the brain has changed over time.

The evolutionary story of the human brain begins where life itself began: the ocean. The brain’s most basic building blocks have existed for billions of years: some of the simplest and oldest single-celled organisms use the same chemical messengers that our own brain and nervous system depend on. Sponges, one of the earliest groups of animals to have evolved, do not have nervous systems, but they do have some of the same genes and proteins that are essential for the construction of neural connections in our brain. The cells in a sponge’s body also communicate with waves of calcium ions not unlike the cascades of charged particles that surge down neurons in more complex animals. Jellyfish and their gelatinous relatives may have been the first group of animals to evolve genuine neurons—long, thin, branching cells adapted for the task of transmitting messages from one part of animal’s body to another. But these neurons were arranged in a diffuse net that enveloped the animals’ bodies. There was no central processor, no intricate organization, no brain. The next major chapter in the brain’s evolutionary history was a process known as cephalization, in which neurons cluster at one end of an animal, eventually becoming a brain linked to important sensory organs like eyes. Cephalization probably happened several times, and in different ways, in different groups of animals. Within the tiny, simple brains of worms and fish, particular brain regions began to specialize in different functions—one region largely devoted itself to vision, the precursor to our occipital lobe, while another focused on responding to threats, the progenitor of the amygdala. Even before life left the water, animals had evolved brains with much of the same basic neural architecture that we would eventually inherit.

Studying the brain and mind in ignorance of this vast evolutionary tale does not make sense. It would be equivalent to an archaeologist discovering the remains of an enormous tapestry, slicing out a particular figure from the cloth and claiming that he could learn everything he needs to know by examining that figure in isolation. Even if the archaeologist described the figure in exquisite detail, taking it apart thread by thread and sewing it back together, he would remain willfully oblivious of the whole story. In the same way, disregarding the human brain’s history limits psychology and neuroscience to a paltry understanding of our brains and minds.

With regard to our brain’s tumultuous past, evolutionary psychology is primarily concerned with what happened to the human brain during the Paleolithic, between about 2.6 million and ten thousand years ago. Gottlieb is right that evidence of Paleolithic psychology is scant, but it’s not nonexistent. Learning about the brains and behaviors of early humans is a difficult challenge, but not an impossible one [PDF]. By measuring fossil skulls—and creating models of the brains they once held—anthropologists have established that brain size tripled over the course of human evolution. The trend kicks off around 2 million years ago and the swiftest growth occurred between 800,000 and 200,000 years ago during a period of rapid shifts in climate. The National Museum of Natural History has a graph plotting changes in braincase volumes of early humans against changes in the climate. Anthropologists think that early humans with the largest brains adapted most effectively to such a mercurial climate.

Around 100,000 years ago, the human brain largely stopped expanding (and some evidence suggests it has actually shrunk a little since then). What scientists have not yet satisfactorily answered is exactly why the human brain began to swell in the first place and what benefits larger brains offered our ancestors. The most intuitive and tempting explanation is that the expansion of our brains during the Paleolithic paralleled the emergence of more sophisticated intelligence, as partially evidenced by the existing archaeological record of increasingly complex tools and cookware. Learning to cook with fire dramatically improved our ancestors’ diet—it’s much easier to digest and extract calories from soft, cooked foods than from raw, tough foods. In turn, a more nutritious diet likely fueled brain growth. As early human populations increased and spread across the globe, an increasingly diverse social environment would also have demanded a larger and more comlex brain.

One potentially distinct species of hominin called Homo floresiensis, also known as the Hobbit, bucked the trend of bigger brains. Although H. floresiensis went extinct relatively recently, only around 12,000 years ago, it stood just over three feet tall and boasted a brain only half the size of its predecessor, Homo erectus, and one third the size of our modern brains. Yet the remains of H. floresiensis have been discovered alongside evidence of butchery with stone tools and cooking with fire. How, then, do we reconcile the Hobbit’s small brain with evidence of such high intelligence? Is it structure, not size, that matters most? This is exactly the kind of evolutionary puzzle we need to solve to thoroughly understand the human brain and mind. The more we learn about the brains of early humans—and what those brains were capable of—the better we understand our modern minds.

Toward the end of his review, Gottlieb writes: “To confirm any story about how the mind has been shaped, you need (among other things) to determine how people today actually think and behave, and to test rival accounts of how these traits function. Once you have done that, you will, in effect, have finished the job of explaining how the mind works. What life was really like in the Stone Age no longer matters. It doesn’t make any practical difference exactly how our traits became established. All that matters is that they are there.”

Once again, Gottlieb proposes that understanding “how the mind works” is more important than understanding “how the mind has been shaped”—that once you have achieved the former, you need not bother with the latter. One could take a supremely utilitarian approach to the study of the brain and mind, confining oneself to research with explicit practical applications. All Why questions are off the table! We only care about how the mind works. Just explain what happens and move on. No need to think about what any of it means. To be perfectly honest, that sounds unbearably boring to me. More fundamentally, understanding how the mind works and why it works that way are indivisible goals. The human brain’s evolutionary past is not just some cute story we can leave on the shelf if we so please. Every cell in our brains—every moment of our mental lives—is intimately connected to the entire history of life on this planet.

Campylobacter bacteria (Image by Agricultural Research Service, via Wikimedia Commons)

There’s a food fight in your guts. Not the Tater-Tot-chucking, spoonful-of-mashed potato-flinging, melee-in-the-cafeteria type of food fight. Rather, your intestines are the site of an ancient and complex war between your own cells and trillions of bacteria—a war over what happens to your food as it moves through your body. Some of the bacteria form genuine alliances with your intestinal cells, breaking down tough plant fibers that your cells cannot handle on their own, or chopping up lengthy caterpillar molecules into more digestible packages, in exchange for a portion of the day’s calories. Other bacteria lurk and loiter, sipping the nutrient-rich broth sloshing in your intestines as they wait for their chance to overrun your guts at the expense of your health. Every day, these microorganisms squabble amongst themselves for greater access to available nutrients. And sometimes your cells fight back, working extra hard to digest the food you eat before those persistent microbes help themselves to a disproportionately large serving. Studies suggest that the diversity of bacterial species in our guts partially determines how efficiently our cells process and store food and that, in a feedback loop, what we eat alters the demographics of the bacteria in our intestines. Commonly prescribed antibiotics are responsible for unintended microbial casualties, further changing how our resident population of microorganisms responds to our diet. Although scientists are still figuring out the rules of this intricate food fight, it’s evident by now that our guts are not entirely our own—they are composite organs, part-human, part-microbe, which evolved, and continue to function, as communities whose many minute members are sometimes cooperative, sometimes combative and always hungry.

A study published this week adds nuance to scientists’ evolving understanding of how gut bacteria change the way animals digest food. Ivana Semova and John Rawls of the University of North Carolina at Chapel Hill, along with their colleagues, studied the absorption of fluorescent fatty acids in the intestines of tiny translucent zebrafish (Danio rerio). Compared to zebrafish raised in germ-free environments, zebrafish whose guts were colonized by bacteria absorbed more fat from their diets. And the more the fish ate, the larger the population of bacteria in their guts. In particular, eating encouraged the growth of a tribe of bacteria known as Firmicutes, which in turn increased the number of energy-rich fat bubbles stored within the fish’s intestinal cells for later use. Studies with people and mice have also shown that high-calorie diets stimulate the growth of Firmicutes in the gut, hinting that this particular group of bacteria may respond to its host’s diet in similar ways across many different species. What remains unclear is whether Firmicutes helps animals absorb more calories from their food in a mutually beneficial partnership or if the relationship is more complex—and sometimes less than benevolent.

Bacteria constitute between 40 and 60 percent of the dry weight of human feces, with trillions of cells in every gram. Zebrafish intestines are not home to the exact same species of bacteria that live in our own guts, but—if you take a broad enough view of the communities—they have a surprising amount of overlap. Both communities are dominated by the phyla Proteobacteria, Firmicutes, and Bacteroidetes (phylum is the taxonomic level below kingdom). Young zebrafish are also particularly convenient for scientists who want an inside look on the digestive process because day-old zebrafish are transparent—you you can see everything that is happening in their intestines under a microscope without the need for a damaging and disruptive dissection.

Semova and Rawls chemically bonded fluorescent molecules to two common fatty acids, palmitic acid pentanoic acid, and mixed the glowing fats into the egg yolk of embryonic zebrafish. The intestinal cells of zebrafish that were exposed to bacteria as they developed glowed more brightly than the intestinal cells of zebrafish that were raised in sterile environments, indicating that zebrafish guts squirming with bacteria absorbed more fat. The intestinal cells of zebrafish with healthy populations of gut bacteria, collectively known as gut microbiota, also contained larger lipid droplets—bubbles of fat stored as expedient sources of energy.

In the presence of bacteria, zebrafish intestinal cells (red) absorb more fatty acids and package larger lipid droplets (green). Well-fed zebrafish with healthy bacterial populations package the most lipid droplets of all. Image created by Ivana Semova, UNC

The number of lipid droplets in the fish’s intestinal cells depended on their diet. Fish with bacteria in their guts and a steady source of food had much higher numbers of lipid droplets in their intestinal cells than fish that were denied food for a few days. Eating specifically promoted the growth of bacterial species in the phylum Firmicutes and this increase was not reflected by changes in the numbers of bacteria in the surrounding water. Eating changes a fish’s internal ecosystem. The more a zebrafish eats, the more Firmicutes in its guts. And the more Firmicutes in a zebrafish’s guts, the more efficiently its intestinal cells absorb fat.

To investigate how Firmicutes stimulates fat absorption, Semova and Rawls grew different strains of bacteria in different liquid media, which you can think of as a kind of broth. After filtering out the bacteria, they exposed baby zebrafish to the different media. Only media from Firmicutes significantly increased the number of lipid droplets in the fish’s intestinal cells, suggesting that whatever proteins or molecules those bacteria secreted into the media somehow enhanced fatty acid absorption. The results were published September 13 in Gut Host & Microbe.

These findings mirror the conclusions of many previous studies, which have shown, for example, that starving mice for a single day reduces the population of Firmicutes in their guts and that transplanting Firmicutes from obese mice into the germ-free intestines of lean mice makes the thin rodents plump. When obese people begin a low-fat or low-carb diet, Bacteroidetes proliferates and Firmicutes dwindles. Clearly, Firmicutes is happiest when we are eating a lot. One pertinent and unanswered question is whether we should share that happiness. Are Firmicutes graciously helping us extract more calories from our food, taking only a modest cut for themselves? Are they selfishly increasing their own numbers when the eating is good, forcing our cells to sweat to get the most out of our food? Are they in fact making digestion too easy, liberating so many calories from our food that we absorb far more than we need? Perhaps there is truth in all these scenarios.

“We are in the midst of a revolution of our ability to describe the composition and physiological potential of these bacterial communities,” Rawls says. “What we can begin to speculate on, though, are the different types of relationships that might be taking place. We know gut microbiota enhance our ability to extract calories from complex carbohydrates, which is clearly a mutually beneficial relationship. But it’s thought that all vertebrates have the capacity to digest and absorb other types of nutrients, such as lipids, proteins and simple carbohydrates, so it’s not readily clear how we could enter into a mutually beneficial relationship with bacteria with regard to those nutrients. When we see fatty acid absorption increased in zebrafish, that may be selfish or defensive response. Perhaps the fish recognizes the presence of more bacteria and increases its own fatty acid absorption. It may not always be such a friendly arrangement.”

A Photoshopped image of an ideal, but improbable, fruit salad tree (Credit: Adapted from various Wikimedia images by Guety, Fir0002/Flagstaffotos, Tobias and MikeyMoose)

In an episode of Matt Groening’s animated science fiction sitcom Futurama, Leela offers her friend Fry an unusual housewarming gift: a bonsai tree sprouting tiny bananas, melons and plums. “It’s a miniature fruit salad tree,” she explains.

Here’s the thing: fruit salad trees are real.

In Australia, James and Kerry West grow and sell four types of fruit salad trees, each of which bears several different kinds of fruit. Stone fruit salad trees grow peaches, plums, nectarines, apricots and peachcots. Citrus salad trees offer a winter and summer orange, mandarins, lemons, limes, grapefruits, tangelos and pomelos. Multi-apple trees boast between two and four different kinds of apples and multi-nashi trees produce between two and four different kinds of Asian pears.

In an online video, Kerry West explains how her husband James created their first fruit salad trees more than twenty years ago by learning the craft of grafting. “He started putting the different fruits but of the same family and seeing what would happen if you grafted them all onto the one tree,” Kerry says in the video. “We were amazed at the results.”

Grafting unites the tissues of two or more plants so that they grow and function as a single plant. One plant in the graft is called the rootstock, selected for its healthy or hardy root system. The other plant or plants, chosen for their fruit, flowers or leaves, are known as scions. You can join a scion to a rootstock in many different ways. In one of the most common techniques, you remove a branch from a plant whose fruit you want to reproduce and cut the broken end of the branch into a V-shape not unlike the reed for a woodwind. Shaving the scion in this way exposes its vascular cambium—a ring of plant tissue full of dividing cells that increase the branch’s girth. Once the scion is ready, you slice lengthwise into a branch on the rootstock—exposing its vascular cambium—and wedge the scion into the cleft. Successful grafting requires placing the vascular cambia of both the rootstock and scion in close contact. Another grafting method involves cutting small pockets between the rootstock’s bark and cambium and slipping scions into those pouches. To seal the deal, you bind the scion and rootstock with a rubber band, tape, staples, string or wax.

Click to enlarge (Credit: Ferris Jabr; adapted from photo by J.smith, via Wikimedia Commons)

Over the next few weeks, the scion and rootstock fuse their internal tissues and grow thickened scar tissue around the graft. First, both plants kill and wall off damaged cells. Meanwhile, callus cells in the vascular cambia proliferate and cement themselves together with sticky proteins, forming a living link between scion and rootstock known as the “callus bridge.” If you were to look from above at a cross-section of a cleft graft undergoing this process, it would look something like an intact slice of kiwi—the scion—jammed between the separated halves of another kiwi slice—the rootstock—with the living threads of the callus bridge merging the middle kiwi slice with the semicircles on its flanks. Callus cells also provide temporary links between the primary vascular tissues in the scion and rootstock—the xylem, which transports water, and the phloem, which carries sugars. Eventually, the vascular cambia builds brand new xylem and phloem that unite scion and rootstock into a single functional organism (Reference: Plant Propagation: Principles and Practices).

Farmers have been grafting fruit trees and other crops for thousands of years, but most grafts involve only two plants. The basic idea is to attach whatever kind of plant you want to grow onto a root system that is well adapted to the local soil. As John McPhee explains in his book Oranges:

“In Florida, most orange trees have lemon roots. In California, nearly all lemon trees are grown on orange roots. This sort of thing is not unique with citrus. With the stone fruits, there is a certain latitude. Plums can be grown on cherry trees and apricots on peach trees, but a one-to-one relationship like that is only the beginning with citrus. A single citrus tree can be turned into a carnival, with lemons, limes, grapefruit, tangerines, kumquats and oranges all ripening on its branches at the same time…Most of the trees on the Ridge [a mountain range in Florida renowned for its orange tree orchards] are growing on Rough Lemon…As a rootstock, it forages with exceptional vigor and, in comparison with others, puts more fruit on the tree.”

In addition to increasing yield, grafting can improve resistance to bacteria, viruses and fungi, attract a more diverse group of pollinators and provide a sturdy trunk for delicate ornamental plants. In many cases, grafting is the most reliable way to propagate fruit trees because apples, citrus fruits and many others are not “true to seed”—if you plant the seeds from such fruit, the new generation will not necessarily produce the same fruit as their parents. Instead, you might get something completely different—a grapefruit from a lime, a lemon from an orange—or a genetic surprise.

The main advantage of multi-graft plants like fruit salad trees is convenience. Many people do not have room for several large fruit trees in their backyard, but would ideally like to harvest more than one kind of fruit. Different multi-graft techniques work best for different combinations of species. In general, the more closely related the plants, the more successful the graft. Getting a single tree to bear apples, oranges and bananas is probably too problematic a goal to come to fruition. That’s why the Wests’ fruit salad trees are fusions of related stone fruits or related citrus fruits, but not a mixture of fruits from different botanical families. Other nurseries offer similar multi-graft trees. Ison’s nursery in Georgia sells a multi-graft stone fruit tree that produces peaches, plums, nectarines and apricots. Yamagami’s nursery in California has multi-graft apple and cherry trees. And Stark Bro’s in Missouri sell a 2-N-1 pear tree. Nurseries and hobbyists also graft different types of cacti. Some farmers and gardeners have created pomato plants, which grow potatoes underground and tomatoes above ground. Potatoes and tomatoes might seem very different based on appearances, but they both belong to the genus Solanum (genus is the taxonomic order just above species).

Although grafting woody plants, like fruit trees, is an ancient horticultural technique, grafting soft-stemmed vegetables is a much more recent agricultural practice. Perhaps nurseries will soon start selling mixed vegetable shrubs alongside fruit salad trees. Brassica oleracea seems like a particularly good candidate for such an experiment. This one species includes cabbage, broccoli, cauliflower, Brussels sprouts and kale. Yes, all these plants are cultivars of the exact same species—their appearances and characteristics have been altered through artificial selection over the generations, in the same way people have created so many different dog breeds. A broccauliflower sprouts plant sounds particularly delicious. Maybe it’s time for a family reunion.

'Unemployed Girl' by Russian painter Kazimir Malevich (Wikimedia Commons)

In the opening scene of Lena Dunham’s HBO series Girls, the Horvaths tell their 24-year-old daughter Hannah that they will no longer support her—or, as her mother puts it: “No. More. Money.” A recent college graduate, Hannah has been living in Brooklyn, completing an unpaid internship and working on a series of personal essays. The Horvaths intend to give Hannah “one final push” toward, presumably, a lifestyle that more closely resembles adulthood. Hannah protests. Her voice quavers. She tells her parents that she does not want to see them the following day, even though they are leaving town soon: “I have work and then I have a dinner thing and then I am busy—trying to become who I am.”

Across the United States—and in developed nations around the world—twenty-somethings like Hannah are taking longer to finish school, leave home, begin a career, get married and reach other milestones of adulthood. These trends are not just anecdotal; sociologists and psychologists have gathered supporting data. Robin Marantz Henig summarizes the patterns in her 2010 New York Times Magazine feature:

“One-third of people in their 20s move to a new residence every year. Forty percent move back home with their parents at least once. They go through an average of seven jobs in their 20s, more job changes than in any other stretch. Two-thirds spend at least some time living with a romantic partner without being married. And marriage occurs later than ever. The median age at first marriage in the early 1970s, when the baby boomers were young, was 21 for women and 23 for men; by 2009 it had climbed to 26 for women and 28 for men, five years in a little more than a generation.”

These demographic shifts have transformed the late teens through mid twenties into a distinct stage of life according to Jeffrey Arnett of Clark University, who calls the new phase “emerging adulthood.” Arnett acknowledges that emerging adulthood is relevant only to about 18 percent of the global population, to certain groups of twenty-somethings in developed nations such as the United States, Canada, Western Europe, Japan and Australia. To make some broad generalizations, people living in the rest of world—particularly in developing countries—are much more likely to finish formal education in their teens and marry by their early twenties.

Although Arnett primarily studies how society, culture and the economy have created emerging adulthood, some scientists and journalists have wondered whether biology is involved as well. Henig writes that some researchers think a lengthy preamble to adulthood might be “better-suited to our neurological hard-wiring” and that the general ambivalence of twenty-somethings—feeling that they are sort of adults, but not really adults— “reflects what is going on in the brain, which is also both grown-up and not-quite-grown-up.” Most recently, The Wall Street Journal ran an article recommending that concerned parents of twenty-somethings “chill out” because “recent research into how the brain develops suggests that people are better equipped to make major life decisions in their late 20s than earlier in the decade. The brain, once thought to be fully grown after puberty, is still evolving into its adult shape well into a person’s third decade, pruning away unused connections and strengthening those that remain, scientists say.”

After reading The Wall Street Journal article, a flock of questions began flapping in my own twenty-something mind. What does it mean to have a “fully grown” adult brain anyways and, if my peers and I do not yet have such a brain, exactly how un-grown-up are our noggins, how uncooked our noodles? Were we neurologically unfit to make the important decisions about careers and marriage that some of us have already made? If emerging adulthood is itself an emerging phenomenon, what is its precise relationship to the biology of an organ whose defining characteristics began evolving millions of years ago? And does a Peter Pan brain have any redeeming qualities?

Budding brains
In an ongoing study that kicked off in 1991, Jay Giedd of the National Institute of Mental Health has been tracking the brain development of nearly 4,000 people ranging in age from a few days to 96 years. Every two years, Giedd invites his volunteers to the lab to scan their brains with magnetic resonance imaging (MRI). Giedd and his colleagues have learned that, contrary to neuroscientists’ earliest assumptions, the brain continues to markedly rewire itself even after puberty.

Between 12 and 25, the brain changes its structure in a few important ways. Like an overeager forest, neurons in the early adolescent brain become bushier, growing more and more overlapping branches whose twigs reach toward one another, nearly touching except for tiny gaps known as synapses. When an electrical impulse—or action potential—reaches a twig, the neuron flings spurts of chemical messages across the synapse. Over time, depending on how teens busy their minds, twigs around the least used synapses wither, while twigs flanking the most trafficked synapses grow thicker, strengthening those connections. Meanwhile, as neurons in the adolescent brain make and break connections, glia—non-firing brain cells—set to work wrapping neurons in a fatty white tissue known as myelin, considerably increasing the speed at which electrical impulses travel along neurons’ branches.

Although these developmental changes continue far longer than researchers initially thought, they are not as dramatic in the twenties as they are in the teens. “In the twenties, the brain is definitely still changing, but it’s not rampant biological change,” explains Beatriz Luna of the University of Pittsburgh. “Most of the brain’s systems are good to go in one’s twenties.” In an email message, B.J. Casey of Weill Cornell Medical College made a similar remark: “Most of my functional imaging work shows the greatest brain changes between 13 and 17 with relative stability across 20s.”

In her own studies, Luna has found that, at least on certain cognitive tasks, people in their early twenties perform just as well as people in their late twenties. She often asks her volunteers to deliberately look away from a flashing light on a screen—a test of impulse inhibition, since flickers attract our attention. “Ten-year-olds stink at it, failing about 45 percent of the time,” as David Dobbs put it in his National Geographic feature. “Teens do much better. In fact, by age 15 they can score as well as adults if they’re motivated, resisting temptation about 70 to 80 percent of the time…And by age 20, their brains respond to this task much as the adults’ do.”

In Luna’s studies, brain behavior changed in parallel with improving scores. Older volunteers showed higher activity in brain regions involved in identifying errors, such as the anterior cingulate cortex. Related research has shown that older adolescents have stronger bridges of neural tissue connecting the emotional and motor centers of their brains with the prefrontal cortex, an “executive” brain region known for, among many other things, inhibiting impulses and tempering bubbling emotions. Luna and other researchers now think that, more than the growth of any single brain region, this increasing interconnectedness characterizes brain development in the twenties. Of course, that doesn’t mean that once someone leaves behind their twenties they will never again lose their cool or act thoughtlessly instead of prudently. Individual variation makes all the difference. Some teens and twenty-somethings are simply more cautious and composed than some adults.

To reflect the ongoing structural changes in the adolescent and twenty-something brain, many journalists and scientists use words and phrases like “unfinished,” “work in progress,” “under construction” and “half-baked.” Such language implies that the brain eventually reaches a kind of ideal state when it is “done.” But there is no final, optimal state. The human brain is not a soufflé that gradually expands over time and finally finishes baking at age 30. Yes, we can identify and label periods of dramatic development—or windows of heightened plasticity—but that should not eclipse the fact that brain changes throughout life.

Studies have confirmed, for example, that London taxicab drivers grow larger hippocampi as they learn to navigate London’s convoluted roadways. This growth in the hippocampus, a brain region essential for forming new memories, is not explained by youth: According to the Public Carriage Office, 98 per cent of London taxi drivers are over the age of 30 [PDF]. Granted, the hippocampus is one of only two regions thought to grow new neurons in adulthood, but the brain remains remarkably plastic in other ways too. When one part of the brain shrivels—say, from stroke or traumatic injury—nearby regions often adopt their deceased neighbor’s functions. When blind people learn to use echolocation, areas of their brains usually devoted to vision learn to interpret the echoes of clicks and taps instead. Neuroplasticity is an everyday phenomenon as well. The adult brain constantly strengthens and weakens connections between its cells. In fact, learning and memory are dependent on such flexibility. Learning a new language or picking up an instrument may be easier when one is young, but adaptability and creativity do not expire on one’s 30th birthday.

Brains of our past and present
Mapping structural changes in the brain over time tells us how the brain matures, but not why it matures that way. To answer why we have to think about the benefits that prolonged brain development would have offered our ancestors. After all, the human brain’s fundamental phases of development could not have popped into existence in the last 50 years or even thousands of years ago—more likely, they evolved at least a couple million years ago in the Paleolithic, when the human brain began to increase in size and morph into the organ we know today. Keeping the brain extra flexible for a longer period of time may have provided our ancestors with more opportunities to quickly master new skills and adapt to a changing environment. But taking too long to learn how to manage emotions, control impulses and plan ahead may also have impeded survival.

Painting an accurate tableau of the Paleolithic lifestyle is difficult because the evidence is scant, but we can say a few things with confidence. First, although the exact lifespans of early humans are not certain, evidence from the fossil record—as well as death rates among modern hunter-gatherer societies—suggests that most early humans did not live as long as people in developed nations today. Children frequently died in their first years of life. If you made it to 15, you were more likely to live at least another 15 or 20 years, but people who lived past their forties were probably in a minority. Second, early humans likely started having children far sooner than people in industrialized countries today. Paleolithic twenty-somethings, we can safely assume, did not have the luxury of spending a few years after college “finding themselves” while backpacking through India and volunteering on organic farms. Rather, people who survived to their twenties in the Paleolithic probably had to bear the responsibilities of parenthood as well as contribute substantially to their community’s survival. These are not exactly circumstances that favor leisurely cognitive development late into one’s twenties.

When I described this scenario to Giedd, however, he suggested that widening the window of heightened neuroplasticity to encompass one’s twenties may have helped Homo sapiens adapt to rapid shifts in the climate. Unfortunately, as with many hypotheses in evolutionary psychology, scientists do not have a way to objectively test these ideas. Still, if we want to fully understand the brain, we cannot ignore the fact that it evolved in circumstances very different from our own.

For now, let’s put the brains of ancient twenty-somethings out of our minds. What about the twenty-somethings of today? Even if the brain’s developmental changes are more dramatic in the teens than in the twenties, the best available evidence suggests that a twenty-something’s brain boasts a little more adaptability than an older brain. Our twenties might represent a final opportunity to begin mastering a particular skill with a kind of facility we cannot enjoy in later decades. Should people in their twenties buckle down and choose something, anything, to practice while their brains are still nimble? Does the neuroscience suggest that, for all their freedom and fun, gallivanting twenty-somethings neglect their last years of heightened plasticity? Should parents encourage their 20-year-olds to shirk adult responsibilities lest they hamper an advantageous period of self-discovery and wild experimentation?

Solid neuroscience that can directly answer these questions does not yet exist. “It’s too soon to tell,” Giedd says, “but we’re wondering.” He and his colleagues plan to compare the brain development of girls who become pregnant in their teens to girls who do not. “Teen pregnancy changes all your priorities and what you do with your time—how do those experiences change the brain?” Arnett agrees that such neuroimaging studies would be useful. “Even in industrialized countries, a lot of people still get married pretty early. You could do brain studies comparing people who experience their twenties differently and contrast how their brains develop.”

In the meantime, twenty-somethings can expect increasingly frequent waves of sage advice from academics, bloggers and concerned parents alike. “Watching talking cats on YouTube isn’t as good for cognitive development as reading or taking classes,” Laurence Steinberg of Temple University told The Wall Street Journal. Truth. In the same article, Jennifer Tanner, co-chair of the Society for the Study of Emerging Adulthood, provides her own pearl: “My advice is, if your parents are currently doing things for you that you could do for yourself, take the controls. Say, ‘No. Mom, Let me get my own shampoo.’” Thanks for the tip, Ms. Tanner. I mean, if I were living at home to save money, I wouldn’t mind sharing the jumbo size 2-in-1 shampoo and conditioner with my siblings. But I’m pretty sure the vast majority of my peers have a handle on shampoo selection by now. Because we’re worth it.

Emerging adulthood is real—it’s happening, albeit to a small percentage of the world’s population. Whether we can, at this moment in time, meaningfully link this life stage to neuroscience seems a tenuous proposition at best. By itself, brain biology does not dictate who we are. The members of any one age group are not reducible to a few distinguishing structural changes in the brain. Ultimately, the fact that a twenty-something has weaker bridges between various brain regions than someone in their thirties is not hugely important—it’s just one aspect of a far more complex identity.

(Image by David R. Ingham, via Wikimedia Commons)

The computer, smartphone or other electronic device on which you are reading this article has a rudimentary brain—kind of.* It has highly organized electrical circuits that store information and behave in specific, predictable ways, just like the interconnected cells in your brain. On the most fundamental level, electrical circuits and neurons are made of the same stuff—atoms and their constituent elementary particles—but whereas the human brain is conscious, manmade gadgets do not know they exist. Consciousness, most scientists argue, is not a universal property of all matter in the universe. Rather, consciousness is restricted to a subset of animals with relatively complex brains. The more scientists study animal behavior and brain anatomy, however, the more universal consciousness seems to be. A brain as complex as the human brain is definitely not necessary for consciousness. On July 7 this year, a group of neuroscientists convening at Cambridge University signed a document officially declaring that non-human animals, “including all mammals and birds, and many other creatures, including octopuses” are conscious.

Humans are more than just conscious—they are also self-aware. Scientists differ on the difference between consciousness and self-awareness, but here is one common explanation: Consciousness is awareness of one’s body and one’s environment; self-awareness is recognition of that consciousness—not only understanding that one exists, but further understanding that one is aware of one’s existence. Another way of thinking about it: To be conscious is to think; to be self-aware is to realize that you are a thinking being and to think about your thoughts. Presumably, human infants are conscious—they perceive and respond to people and things around them—but they are not yet self-aware. In their first years of life, infants develop a sense of self, learn to recognize themselves in the mirror and to distinguish their own point of view from other people’s perspectives.

Numerous neuroimaging studies have suggested that thinking about ourselves, recognizing images of ourselves and reflecting on our thoughts and feelings—that is, different forms self-awareness—all involve the cerebral cortex, the outermost, intricately wrinkled part of the brain. The fact that humans have a particularly large and wrinkly cerebral cortex relative to body size supposedly explains why we seem to be more self-aware than most other animals.

The structure of the human brain (Image courtesy of the National Institute for Aging, via Wikimedia Commons)

One would expect, then, that a man missing huge portions of his cerebral cortex would lose at least some of his self-awareness. Patient R, also known as Roger, defies that expectation. Roger is a 57-year-old man who suffered extensive brain damage in 1980 after a severe bout of herpes simplex encephalitis—inflammation of the brain caused by the herpes virus. The disease destroyed most of Roger’s insular cortex, anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC), all brain regions thought to be essential for self-awareness. About 10 percent of his insula remains and only one percent of his ACC.

Roger cannot remember much of what happened to him between 1970 and 1980 and he has great difficulty forming new memories. He cannot taste or smell either. But he still knows who he is—he has a sense of self. He recognizes himself in the mirror and in photographs. To most people, Roger seems like a relatively typical man who does not act out of the ordinary.

Carissa Philippi and David Rudrauf of the University of Iowa and their colleagues investigated the extent of Roger’s self-awareness in a series of tests. In a mirror recognition task, for example, a researcher pretended to brush something off of Roger’s nose with a tissue that concealed black eye shadow. 15 minutes later, the researcher asked Roger to look at himself in the mirror. Roger immediately rubbed away the black smudge on his nose and wondered aloud how it got there in the first place.

Philippi and Rudrauf also showed Roger photographs of himself, of people he knew and of strangers. He almost always recognized himself and never mistook someone else for himself, but he sometimes had difficulty recognizing a photo of his face when it appeared by itself on a black background, absent of hair and clothing.

Roger also distinguished the sensation of tickling himself from the feeling of someone else tickling him and consistently found the latter more stimulating. When one researcher asked for permission to tickler Roger’s armpits, he replied, “Got a towel?” As Philippi and Rudrauf note, Roger’s quick wit indicates that in addition to maintaining a sense of self, he adopts the perspective of others—a talent known as theory of mind. He anticipated that the researcher would notice his sweaty armpits and used humor to preempt any awkwardness.

In another task, Roger had to use a computer mouse to drag a blue box from the center of a computer screen towards a green box in one of the corners of the screen. In some cases, the program gave him complete control over the blue box; in other cases, the program restricted his control. Roger easily discriminated between sessions in which he had full control and times when some other force was at work. In other words, he understood when he was and was not responsible for certain actions. The results appear online August 22 in PLOS One.

Given the evidence of Roger’s largely intact self-awareness despite his ravaged brain, Philippi, Rudrauf and their colleagues argue that the insular cortex, anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC) cannot by themselves account for conscious recognition of oneself as a thinking being. Instead, they propose that self-awareness is a far more diffuse cognitive process, relying on many parts of the brain, including regions not located in the cerebral cortex.

MRI images of a child with hydranencephaly (Image via Behavioral and Brain Sciences via American College of Radiology)

In their new study, Philippi and Rudrauf point to a fascinating review of children with hydranencephaly—a rare disorder in which fluid-filled sacs replace the brain’s cerebral hemispheres. Children with hydranencphaly are essentially missing every part of their brain except the brainstem and cerebellum and a few other structures. Holding a light near such a child’s head illuminates the skull like a jack-o-lantern. Although many children with hydranencephaly appear relatively normal at birth, they often quickly develop growth problems, seizures and impaired vision. Most die within their first year of life. In some cases, however, children with hydranencephaly live for years or even decades. Such children lack a cerebral cortex—the part of the brain thought to be most important for consciousness and self-awareness—but, as the review paper makes clear, at least some hydranencephalic children give every appearance of genuine consciousness. They respond to people and things in their environment. When someone calls, they perk up. The children smile, laugh and cry. They know the difference between familiar people and strangers. They move themselves towards objects they desire. And they prefer some kinds of music over others. If some children with hydranencephaly are conscious, then the brain does not require an intact cerebral cortex to produce consciousness.

Whether such children are truly self-aware, however, is more difficult to answer, especially as they cannot communicate with language. In D. Alan Shewmon‘s review, one child showed intense fascination with his reflection in a mirror, but it’s not clear whether he recognized his reflection as his own.  Still, research on hydranencephaly and Roger’s case study indicate that self-awareness—this ostensibly sophisticated and unique cognitive process layered upon consciousness—might be more universal than we realized.

*If you printed out this article, kudos and thanks for reading!

References

Merker B (2007) Consciousness without a cerebral cortex: A challenge for neuroscience and medicine. Behavioral and Brain Sciences 30: 63-81.

Philippi C., Feinstein J.S., Khalsa S.S., Damasio A., Tranel D., Landini G., Williford K.5, Rudrauf D. Preserved self-awareness following extensive bilateral brain damage to the insula, anterior cingulate, and medial prefrontal cortices. PLOS ONE. Aug 22.

Shewmon DA, Holmes GL, Byrne PA. Consciousness in congenitally decorticate children: developmental vegetative state as self-fulfilling prophecy. Dev Med Child Neurol. 1999 Jun;41(6):364-74.

An icefish larva (Credit: Uwe kils, Wikimedia Commons)

In 1928, a biologist named Ditlef Rustad caught an unusual fish off the coast of Bouvet Island in the Antarctic. The “white crocodile fish,” as Rustad named it, had large eyes, a long toothed snout and diaphanous fins stretched across fans of slender quills. It was scaleless and eerily pale, as white as snow in some parts, nearly translucent in others. When Rustad cut the fish open, he discovered that its blood, too, was colorless—not a drop of red anywhere. The crocodile fish’s gills looked odd as well: they were soft and white, like vanilla yogurt; in contrast, a cod’s gills are as dark as wine, soaked in oxygenated blood.

Later, Johan Ruud and other researchers confirmed that the Antarctic icefishes, as they are now known, are the only vertebrates that lack both red blood cells and hemoglobin—the iron-rich protein such cells use to bind and ferry oxygen through the circulatory system from heart to lungs to tissues and back again. At first blush, biologists regarded icefishes’ pallor blood as a remarkable adaptation to the Antarctic’s freezing, oxygen-rich waters. Perhaps icefishes absorbed so much dissolved oxygen from the ocean through their gills and ultra thin skin that they could abandon those big, spongy red blood cells. After all, the biologists reasoned, thinner blood requires less effort to circulate around the body and saving energy is always an advantage, especially when you are trying to survive in an extreme environment.

More recently, however, some biologists have proposed that the loss of hemoglobin was not a beneficial adaptation, but rather a genetic accident with unfortunate consequences. Since icefish blood can only transport 10 percent as much oxygen as typical fish blood, icefishes were forced to dramatically alter their bodies in order to survive. In this scenario, despite an evolutionary blunder that would be lethal to most fish, the icefishes’ grit—as well as a little ecological serendipity—rescued them from their own bad blood. Scientists continue to revise icefishes’ evolutionary history as new evidence surfaces, but their story is surely one of the most unique and bizarre in the animal kingdom.

Icefishes live in the Southern Ocean, which encircles Antarctica. Rotating currents essentially isolate these waters from the world’s warmer seas, keeping temperatures low: temperatures near the Antarctic Peninsula, the northernmost part of the mainland, range from about 1.5 degrees Celsius in the summer to –1.8 degrees Celsius in the winter. Many fish in the Southern Ocean, including icefishes, produce antifreeze proteins to prevent ice crystals from forming in their blood when ocean temperatures drop below the freezing point of fresh water. Sixteen species of Antarctic icefishes comprise the family Channichthyidae, which falls under the larger suborder Notothenioidei. Among the hundreds of red-blooded Notothenioid species, only the icefishes lack hemoglobin. Together, the Notothenioids and icefishes dominate the waters they call home, accounting for approximately 35 percent of fish species and 90 percent of fish biomass in the Southern Ocean.

A Blackfin Icefish (Credit: Bill Baker)

By comparing icefish DNA to the DNA of red-blooded fish, William Detrich of Northeastern University and his colleagues identified the specific genetic mutations responsible for the loss of hemoglobin. Basically, one of the genes essential for the assembly of the hemoglobin protein is completely garbled in icefishes. Although no other vertebrate completely lacks red blood cells, biologists have observed a diminishing of red blood cells in response to a changing environment. When it gets cold, it’s advantageous for fish to make their blood a little thinner and easier to circulate. Fish that live in cold waters usually have a smaller percentage of red blood cells in their blood than fish that live in warmer waters. And fish in temperate regions decrease the percentage of red blood cells in their blood each winter to save energy. Relying on these facts, some biologists assumed that Antarctic icefish evolved incredibly thin blood as an adaptation to the Southern Ocean.

Kristin O’Brien of the University of Alaska Fairbanks and her colleague Bruce Sidell (who is now sadly deceased) decided to test this assumption. In a paper titled “When bad things happen to good fish,” O’Brien and Sidell first point out that, compared to their cousins the Notothenioids and other similarly sized fish, icefishes have larger hearts and blood vessels. Although icefishes pump unusually thin blood through their bodies, their circulatory systems handle huge volumes. O’Brien and Sidell calculated that icefishes expend approximately twice as much energy as red-blooded Notothenioids moving all that extra blood. Whereas fish in temperate zones devote no more than five percent of their resting metabolic rate to their hearts, icefishes invest a whopping 22 percent of their body’s available energy in their giant tickers.* O’Brien and Sidell also show that icefish have more blood vessels nourishing certain organs than red-blooded fish. If you peel back the outer layers of a typical fish’s eye and fill the blood vessels with yellow silicone rubber, you will see a web of neatly segregated vessels tracing the contour of the eye like the ribs of a pumpkin. Do the same to an icefish’s eye and you will find a dense, tangled mess like a plate of spaghetti.

Like other biologists in recent years, O’Brien and Sidell view the icefishes’ large hearts and capillaries, high blood volume and dense nets of blood vessels as compensations for the loss of hemoglobin. But these adaptations alone might not have been enough to save icefishes from extinction—they likely benefited from fortuitous circumstances as well. Around 25 million years ago, the Southern Ocean flowing around Antarctica—which had broken away from other continents—began to cool. Not only did the colder water offer more oxygen, it also killed many species that did not evolve antifreeze proteins or otherwise adapt to the cold, creating a frigid sanctuary that the icefishes and their relatives have dominated ever since.

A crocodile icefish (Credit: Marrabbio2, Wikimedia Commons)

Today, however, icefishes face a new threat: manmade climate change. The Southern Ocean is getting warmer and possibly more acidic and less nutritious. O’Brien says researchers have shown that adult icefishes are more sensitive to changes in temperature than red-blooded fish—they cannot stand the heat. If Ruud was right—that “only in the cold water of the polar regions could a fish survive that has lost its pigment”—then the ongoing changes to the Southern Ocean might be the icefishes’ undoing. Consider this version of their story: icefishes evolved to survive sub-freezing temperatures in one of the most extreme environments on Earth, only to lose their red blood cells to a genetic accident; despite the mishap, they kept swimming, expanding their hearts and growing more blood vessels to get enough oxygen around their bodies; now, people are turning the Southern Ocean into a habitat for which icefishes are completely unsuited, forcing them to adapt once again or perish. Personally, I’m clinging to the hope that even if icefishes do not have any hemoglobin in their blood, they have plenty of resilience coursing through their veins.

*Source for cardiac energy investment: Hemmingsen, E. A. and Douglas, E. L. (1977). Respiratory and circulatory adaptations to the absence of hemoglobin in chaenichthyid fishes. In Adaptations within Antarctic Ecosystems (ed. G. A. Llano), pp. 479-487. Washington: Smithsonian Institution.

The medusoid. (Image courtesy of Harvard and Caltech)

This week a team of scientists published a study in Nature Biotechnology* explaining how they created an artificial jellyfish dubbed a ‘medusoid.’ Let’s be clear: scientists have not built a fully functional living jellyfish from scratch. Rather, they have constructed a thin, flower-shaped sheet of rat heart cells and silicone that mimics the swimming behavior of a juvenile moon jellyfish when subjected to an electric current. Since a medusoid cannot move without assistance, cannot eat and cannot reproduce, it does not qualify as a true jellyfish or any other animal for that matter. Still, the achievement suggests new ways to mimic nature in the lab and perhaps even cobble together a functional synthetic life form.

“We have not yet built a true animal or an organism, but what we made is in a sense alive,” explains Kevin Kit Parker of Harvard University who designed the medusoid along with Janna Nawroth and John Dabiri of the California Institute of Technology and their colleagues. “If you keep putting together groups of modified cells, you could make a completely unique life form.”

So let’s try a little thought experiment. What would it take to build a true artificial jellyfish, one that mimics the real thing in every way?

BEGINNINGS
Jellyfish have bloomed and bobbed in the planet’s oceans for at least 500 million years. Compared with animals that evolved later in Earth’s history—like reptiles, birds and mammals—jellyfish are minimalists: they survive just fine with relatively few organs. Like most jellyfish, moon jellies (Aurelia aurita), the species that Parker and his colleagues mimicked in their new study, have no hearts, lungs, gills, circulatory system or skeleton. Instead, seawater suffices, supporting the jelly’s gelatinous body and flowing through its mouth to distribute diffused oxygen and digested food through radial canals. The elegance of such unencumbered bodies makes building an artificial moon jelly less daunting than reconstructing a more complex animal—but it won’t be easy.

MOVING

A comparison of the medusoid and real moon jellyfish (Image courtesy of Harvard and Caltech)

Jellyfish are not the strongest swimmers in the seas—they often drift where the currents take them—but they can steer themselves too. To propel itself through the ocean, a moon jellyfish first pushes against the water by contracting its translucent bell—like an umbrella closing—and subsequently relaxes its muscles until its bell floats upwards to form a flat saucer. Contract, relax, repeat. A medusoid does exactly the same thing, with one crucial difference: Whereas a real jellyfish generates electrical impulses to stimulate its muscle cells, a medusoid is entirely dependent on voltage generated by electrodes in its tank. Moon jellies have eight pacemaker cells scattered around the middle of their bodies (just about every jellyfish body part comes in multiples of four). Pacemaker cells keep the jellies’ muscles pulsating rhythmically. We have pacemaker cells in our hearts that do the same thing. So do rats. Janna Nawroth thinks it’s possible to weave pacemaker cells from a rat’s heart into the heart muscle tissue that makes up a medusoid, which might allow the artificial jellyfish to bob on its own, sans electrodes. The upgrade would rely on a technique known as “co-culturing,” in which different types of cells are grown together. It’s often difficult enough to get one cell type to live happily in the lab, let alone a mixture of different kinds of cells. Think of them as high-maintenance houseplants that are fussy about their neighbors, withering if they do not like their circumstances. Although scientists have not yet mastered co-culturing, they have made impressive advances, cultivating little gardens of gut tissue and bacteria, for example, as well as epithelial cells and immune system cells.

EATING
Even if you get a medusoid to swim on its own, it will soon die unless it has a way to nourish its cells. Artificial jellyfish gotta eat too. As a natural consequence of its swimming behavior, a living moon jellyfish creates tiny vortices beneath its bell—little swirling currents that help its four “oral arms” and stinging tentacles drag nutritious plankton towards its mouth and into its central stomach full of seawater and digestive enzymes. From there, water carries nutrients into enclosed canals that rise up and spread across the jelly’s body, like the branches of a tree.

Since a medusoid swims like a real moon jelly, it too creates eddies beneath its bell, but it has no tentacles, no way to break down food and no channels to distribute that food to its different tissues. Right now, Parker’s medusoid is a two-layered creature of rat cells and silicone. A living jellyfish has three layers: an outer epidermis, an inner gastric lining and, appropriately, a translucent jelly-like middle layer called mesoglea. An artificial jelly would need all three layers to properly contain a stomach and radial canals. Living channels, canals and vessels are notoriously difficult to recreate in the lab, but clever strategies in tissue engineering—particularly with 3D printing—suggest that replicating a jellyfish’s digestive system is not too far-fetched. Tiny hair-like structures called cilia line the canals within a jellyfish’s body, constantly sweeping back and forth to move water and nutrients along. Researchers have in fact constructed artificial cilia that work almost as well as the real thing. Filling a stomach with digestive enzymes or synthetic gastric juice would be pretty easy; getting the stomach to continuously secrete such enzymes would require bona fide stomach cells or genetically modified ones. Tentacles are not essential if the vortices suck up enough water and plankton—but what’s a jellyfish without its stinging skirt?

Moon jellies in Denmark. Notice their four gonads visible through their translucent bells (Credit: Malene Thyssen, via Wikimedia Commons)

SENSING

A lattice of neurons known as a nerve net envelops a moon jelly’s body. In addition to coordinating muscle movement, these cells communicate with receptors that detect light, gravity, touch and chemicals dissolved in the water. Jellyfish do not necessarily need all of these senses to survive, but they certainly help. Besides, a defining characteristic of animals—and most living things, for that matter—is the ability to sense and respond to changes in the environment. An aptitude for detecting light and orienting oneself accordingly—moving toward the light to search for food or away from the shadow of a predator—would be a huge advantage for an artificial jellyfish. The rat heart cells that comprise a medusoid’s body cannot sense light, but scientists have developed a relatively recent technique to endow cells with exactly this talent: optogenetics.

Algae, bacteria and some jellyfish have light-activated ion pumps and channels—proteins that allow charged particles to cross cell membranes. Using viruses to ferry the genes that code for these proteins into blind cells, scientists can make those cells light-sensitive as well. Optegenetics alone is not adequate to make a free-swimming medusoid respond to light with meaningful behaviors. An artificial jellyfish would still need to process that information in some rudimentary way, which requires communication and coordination between the pacemaker cells, heart muscle cells and sensory neurons. And that’s just to provide the artificial jelly with a simple form of vision. Giving it taste and touch would require different sensory neurons that also need to communicate with muscle cells. Despite the absence of a brain and complex central nervous system, a jellyfish’s impressive array of senses would be especially challenging to replicate.

REPRODUCING

Image courtesy of The South Carolina Department of Natural Resources

The largest obstacle to creating a true artificial jellyfish, however, is sex. The ability to reproduce and pass one’s genes to a new generation is perhaps the most fundamental feature of all life on earth. A medusoid is sterile. It has no reproductive organs.

A moon jelly has four such organs, called gonads, which sit below its stomach. When some jellyfish reproduce, the males squeeze sperm through their mouths into the water and females suck it back through their mouths into their ovaries. In other species the females squirt their eggs through their mouths, which hook up with sperm in the open water. Moon jellies keep fertilized eggs on the four oral arms that surround their mouth in a kind of temporary nursery. The resulting larvae swim into the ocean, anchor themselves on the seafloor and grow into coral-like polyps. These polyps begin to bud, forming a column of upside-down juvenile jellyfish that fit into one another like a stack of cereal bowls. Eventually these baby jellies break off one by one and swim away.

Theoretically, one could try to engineer functional gonads onto a medusoid, but that would not accomplish much. Even if you made a male and female medusoid and coaxed them to mate, they would not produce more medusoids. Instead, they would make regular moon jelly babies. After all, their gonads produce sperm and eggs containing the genes for living Aurelia aurita, not for medusoids. A medusoid does not have a functional genome. Successfully quilting a working medusoid genome that codes for a hodgepodge of rat heart cells and light-sensitive neurons is beyond current capabilities. Besides, there are no genes for silicone or artificial cilia. As long as medusoids remain dependent on human engineering and synthetic compounds, they will always be outcasts of sorts, relegated to the fringes of the kingdom of life. That’s probably a good thing.

A group of sea nettles at Monterey Bay Aquarium (Credit: Brocken Inaglory, via Wikimedia Commons)

Creating an artificial jellyfish that could somehow make viable copies of itself is an exciting prospect—but it’s also absolutely terrifying. A few synthetic jellies in the lab might not seem like a huge threat at first. But what if—through well-meaning experiments gone wrong or genuine iniquity—they wound up in the ocean? What if they outcompeted other animals? Enormous blooms of wild jellyfish are already hoarding food supplies and imbalancing ecosystsems. One can envision the headlines: Scientists Create Adorable Artificial Jellyfish. Artificial Jellyfish Goes For Its First Swim. Wow, Artificial Jellyfish Are Doing Really Well For Themselves! Unstoppable Swarms of Synthetic Jellies Overrun the World’s Oceans. Human Leaders Surrender To Gallant, Generous, Gooey Overlords. Get Ready for the Season Premiere of So You Think You Can Wobble?…

It’s not happening now and it’s not happening soon. Remarkable progress in synthetic biology and tissue engineering, however, keeps pushing the possibility of making functional artificial creatures out of the sphere of the improbable and into the open realm of the feasible. Although Parker recognizes that possibility, he makes it clear that true artificial animals—ones that can produce offspring—are not his goal. “That is not my intent,” he says. “I have no interest in making something that reproduces. I do hope what we’ve developed will spur some discussion as to what is responsible and ethical, though.”

Nawroth agrees. “It’s super ambitious to generate a reproductive animal of this degree of complexity. We should just keep them in puberty, stuck at the flirting stage.”

*Scientific American is a part of Nature Publishing Group

(Image via Wikimedia Commons)

On Friday I read a post by novelist and essayist Tim Parks on the New York Review of Books blog. Parks argues that the most memorable character in novels of the twentieth century is “the chattering mind, which usually means the mind that can’t make up its mind, the mind postponing action in indecision and, if we’re lucky, poetry.”

Although I enjoyed Parks’s post overall, I take issue with aspects of his analysis. Twentieth century novels certainly feature many chattering minds—minds that converse with themselves page after page in a mixed language of traditional narration and interior monologue. But what is the basis for Parks’s notion that such minds are chronically constipated, prevented from action by indecision? Parks points to the narrator of Dostoyevsky’s Notes from Underground (first published in 1864), whom he says is “prone to qualification, self-contradiction, interminable complication.” That may be true, but Dostoyevsky’s bitter narrator is not representative of the diverse minds that appear in all novels published between 1900 and 2000. More importantly, qualification and self-contradiction—which feature in any human mind—are not barriers to action, progress or change. Parks would have us believe that twentieth century literature is populated by minds that are always thinking, but never doing, never getting anywhere—minds that whir in angry circles, like a toy race car flipped on its side. But thought is action.

As Clarissa Dalloway hurries about the streets of London, buying flowers and decorations for her party, her mind flies from carriages and motorcars to memories of past romance to thoughts of death and back to a roll of tweed in a shop on Bond Street. Just about every sentence we read is filtered through Clarissa’s mind or one of the other minds in the novel. Woolf rarely describes the world in objective third person, deliberately shifting the focus of her fiction away from external reality toward thought, memory and consciousness. She is interested in what happens inside people’s heads and she knows that so much more can happen in a single moment of mental time than in a moment of linear narrative. Clarissa’s mind is not postponing action of any kind—it continually bustles.

Parks further insists that minds in twentieth century novels demonstrate “monstrously heightened consciousness” and that they are so indecisive and indeterminate precisely because of this “excess of intellectual activity.” Excess? Yes, twentieth century novels boast many brilliant and hyperactive minds. But the novelists most seriously committed to depicting the mind in language did not fixate exclusively on geniuses or madmen or otherwise extraordinary minds. Leopold Bloom does not possess a surplus of intellect. Nor does Mrs. Dalloway. Faulkner inhabits minds of varying intellect, tempo and perspicacity. All these novelists celebrate the complexity of everyday thought—they wanted to portray universal aspects of mental life. If the minds they create seem unusually lively, like pots of soup threatening to bubble over, it is because these novelists recognize and revel in the glorious energy of any human mind and because they lend their own mental fervor to the thoughts of others.

Despite all this supposed excess intellect—or perhaps because of it—the mind remains vulnerable, Parks argues. “Virginia Woolf sounds darker notes,” he writes, “warning us that the mind risks being submerged by the urgent blather of modern life.” This interpretation struck me as particularly odd. “The urgent blather of modern life” is surely a phrase Woolf would have detested. She craved London’s energy, even if she recognized its dangers. The minds in her novels do not drown in their own prattle, nor are they overpowered by the frenzy of modern life—rather, they rejoice in it. Consider these passages from Mrs. Dalloway:

“Such fools we all are, she thought, crossing Victoria Street. For Heaven only knows why one loves it so, how one sees it so, making it up, building it round one, tumbling it, creating it every moment afresh…In people’s eyes, in the swing, tramp, trudge; in the bellow and the uproar; the carriages, motor cars, omnibuses, vans, sandwich men shuffling and swinging; brass bands; barrel organs; in the triumph and the jingle and the strange high singing of some aeroplane overhead was what she loved; life; London; this moment of June.” (P. 4)

“She waved her hand, going up Shaftesbury Avenue. She was all that. So that to know her, or any one, one must seek out the people who completed them; even the places. Odd affinities she had with people she had never spoken to, some woman in the street, some man behind a counter – even trees, or barns. It ended in a transcendental theory which, with her horror of death, allowed her to believe, or say that she believed (for all her scepticism), that since our apparitions, the part of us which appears, are so momentary compared with the other, the unseen part of us, which spreads wide, the unseen might survive, be recovered somehow attached to this person or that, or even haunting certain places after death (P. 153)

Woolf is not sounding dark notes; she is not warning us to protect our precious minds from modern life. Rather, she reveals how the mind invents the world it sees—”creating it every moment afresh”—and how each individual mind, though it may seem an autonomous entity, is in fact inextricable from the world around it, from the minds of others, even from trees and barns. Shared memories emanate from the many minds in Mrs. Dalloway, merging with one another like overlapping ripples on the surface of a pond. Wherever they intersect, they form an invisible web, which is itself enmeshed with the city of London. It is this interconnectedness, this net into which we are woven, that “spreads wide” and saves us from complete annihilation in the end.

If we believe Parks, then Woolf and other twentieth century novelists only invented stream of consciousness “to allow the pain of a mind whose chatter is out of control to be transformed into a strange new beauty, which then encompasses the one action available to the stalled self: suicide.” What a bold and restrictive proclamation about one of the most versatile innovations in literature. In her essays and diaries, Woolf articulated her motivations for trying a new kind of novel—a novel that did not preoccupy itself with verbose descriptions of the physical, but rather with psychological realism. She wanted to remake a living mind in language. Again, Woolf, Joyce, Proust Faulkner and others did not fixate on minds whose chatter was out of control—they invented a new way of writing about the mind, a style that revealed just how wonderfully chaotic, seemingly purposeless and cantankerous an ordinary mind could be. The beauty of their novels is not strange; it is intimately familiar—the same voices we all hear in our heads every day, albeit more eloquent than we have ever known them.

In Parks’s view, a chattering mind is a suffering mind: “Our twentieth century author is simply not interested in a mind that does not suffer.” He explains how, while attending a meditation retreat, it became “all too evident how obsessively the mind seeks to construct self-narrative, how ready it is to take interest in its own pain, to congratulate itself on the fertility of its reflection…But alas, you cannot sit cross-legged without pain unless you learn to relax your body very deeply. And, as neuroscience has recently confirmed, when the mind churns words, the body tenses.”

Twentieth century literature—in fact, literature from every age—is interested in suffering minds, but no era of literature is exclusively interested in mental agony. Woolf, Joyce and Proust penned many painful thoughts—contemplations of suicide, loneliness, self-pity—but they also honored the mind’s moment of triumphs. Sometimes minds in twentieth century novels work hard for their revelations: after struggling to quell self-doubt and the echoes of sexist men who deny her talent, not to mention grappling with the philosophical quandary of objective reality, the young painter Lily Briscoe finally completes her portrait of Mrs. Ramsay—she “has her vision,” if only for a moment, on the very last page of To The Lighthouse. Other times minds stumble onto moments of new understanding, or what Woolf called “little daily miracles, illuminations, matches struck unexpectedly in the dark.”

Psychologists, too, have discovered the benefits of mental chatter, which they call self-talk, private speech or inner voice. Mental rumination is the tendency to mull over one’s frustrations. People who ruminate a lot seem to be especially susceptible to depression, but some psychologists have proposed that a certain level of rumination is advantageous—if we focus on a problem, we are more likely to find a solution. Private speech also plays an important role in the way children learn language and we all rely on self-talk to psych ourselves up before the big game, the job interview or the first date.

More fundamentally, many neuroscientists and psychologists think that without our constant interior monologue—or the mind’s obsessive need to construct self-narrative, as Parks puts it—we would have no sense of self, or at least not the same sense of self most of us understand. Helen Keller wrote that before she learned language, “I did not know that I am. I lived in a world that was a no-world. I cannot hope to describe adequately that unconscious, yet conscious time of nothingness…Since I had no power of thought, I did not compare one mental state with another.” The self is a story we continually revise, just like Clarissa making it all up as she goes along. One of the greatest accomplishments of fiction writers in the twentieth century was learning to recreate this self-narration so realistically that reading their writing feels like slipping into someone else’s mind. Their thoughts become our thoughts. In an earlier post, Parks concludes that we do not need these kinds of novels or any stories for that matter, nor do we need the narrative self. True, we do not need novels the same way we need water, but when it comes to stories, we do not have a choice. We do not wake up one day in toddlerhood and say, “Now I shall begin to tell the story of my Self!” It just happens. Our brains are evolved storytellers.

For me, the choice Parks sets up at the end of his post—the choice between quietness and Roth, between well-being and David Foster Wallace, between mental health and “literary sickness”—is a false choice. I realize Parks might intend a little humor and hyperbole here, but this subject means too much to me to treat so lightly. We should not conflate the narrative mind with suffering, nor quiet with health. Yes, we talk to ourselves—our minds chatter incessantly—and we are all the saner for it.

A fat-tailed dwarf lemur (Image courtesy of Kathrin Dausmann)

In the 18th century Carl Linnaeus named them lemurs, after the Latin lemures—spirits of the dead, wandering ghosts. He knew the primates roamed Madagascar’s forests at night, their large eyes brimming with moonlight, their shrill cries crashing through the treetops. One of the smallest lemurs on the island, the fat-tailed dwarf lemur, resembled a phantom in another way: it completely vanished for seven months each year.

For a long time, no one understood where the fat-tailed dwarf lemur went—a remote part of the island? the spirit world?—or what it was doing all that time, but scientists had a hunch. Perhaps the lemur was hibernating. If so, it would be the only primate in the world—and one of the only tropical mammals—to do so. Given Madagascar’s climate, however, it made sense that a lemur might hibernate to survive annual periods of drought.

In general, Madagascar has two seasons: the hot, wet season from November to April, and the cooler, dry season from April through October. The deciduous forests on the west coast, where many fat-tailed dwarf lemurs live, offer no open sources of water during the dry season and only fibrous fruits bereft of sugar. Perhaps, scientists reasoned, the fat-tailed dwarf lemur hunkered down and waited for the rains to return, slowing its metabolism and dropping its body temperature. It could survive off of nutrients stored in its tail, which always grew plumper as the dry season drew closer.

In 1993 Kathrin Dausmann of the University of Hamburg and her colleagues finally put the hibernation hypothesis to the test. Between 1993 and 2003, the researchers regularly traveled to the forest of Kirindy on the west coast of Madagascar, where they captured 53 fat-tailed dwarf lemurs (Cheirogaleus medius). They tagged all the lemurs with radio transmitters to track their location and implanted six of the primates with small temperature sensors.

Around April, the lemurs disappeared as usual, but they were not really gone—just out of sight. The radio transmitters revealed their hiding spots—nests within tree hollows—and the temperature sensors confirmed that the primates were in fact hibernating during the dry season. The lemurs’ approach to hibernation, however, was unusual.

A fat-tailed dwarf lemur on the west coast of Madagascar (Credit: Frank Vassen, via Wikimedia Commons)

Many small hibernating mammals—including arctic ground squirrels and European hedgehogs—regularly emerge from deep hibernation every few weeks and enter brief periods of biological activity during which their body temperatures rise, their metabolism speeds up and their brain activity increases. The animals do not necessarily get up and move around, but they might urinate and defecate. When they emerge from hibernation, they also sleep. That may seem paradoxical at first; isn’t hibernation a form of deep sleep? No, it’s not. During hibernation the mammalian brain is too cold and too idle to generate the electrical activity that regulates the kind of sleep we look forward to each night. Some scientists think that the need for sleep entirely explains why mammals periodically wake up from hibernation, while others think it is just one reason. What scientists know for certain is that any mammal deprived of sleep for too long will die.

In Dausmann’s study, lemurs hibernating in well-insulated hollows maintained a constant body temperature of about 25 degrees Celsius (77 degrees Fahrenheit), rousing themselves once every 10 to 14 days, somewhat like ground squirrels and hedgehogs. But the body temperatures of lemurs inside poorly insulated hollows fluctuated by 20 degrees Celsius or more every day with the ambient temperature, which increased from 10 degrees Celsius (50 degrees Fahrenheit) or colder at night to 30 degrees Celsius (86 degrees Fahrenheit) or warmer during the day. No one had ever observed such passive hibernation in a mammal. Dausmann thinks the primates essentially return to a reptilian form of temperature regulation, relinquishing control of their body’s thermostat to the environment and sparing themselves the energetic cost of waking up periodically during hibernation. The sun does most of the work for them.

In recent years, Peter Klopfer of Duke University and his colleagues have been visiting the forest of Kirindy on Madagascar to learn more about fat-tailed dwarf lemurs. Klopfer is particularly interested in studying how the dwarf lemur’s brain copes with hibernation. As a primate brain, the lemur’s brain is larger relative to body size, more complex and more demanding of energy than a squirrel’s brain. Klopfer and his teammates observe lemurs at the Duke Lemur Center and set up nesting boxes on Madagascar. They measure how much oxygen the lemurs use while inside their boxes as a proxy for changes in body temperature, as well as implanting temperature sensors just below the skin. The researchers also slip small, slender electrode needles below the lemurs’ scalps to measure electrical activity in their brains.

A fat-tailed dwarf lemur with a plump tail (Image courtesy of Kathrin Dausmann)

So far, their data suggests that the hibernating fat-tailed dwarf lemur brain is unique among all hibernators, orchestrating sleep patterns that look nothing like those of ground squirrels or other hibernating mammals.

In people and most other mammals, rapid eye movement (REM) sleep—the phase most strongly associated with dreams—occupies about 25 percent of a night’s sleep. This is true for fat-tailed dwarf lemurs that are not hibernating. Klopfer and his team discovered that when hibernating dwarf lemurs sleep, however, they exclusively enter REM-sleep and they stay in REM sleep for an unusually long time. Arctic ground squirrels, in contrast, rarely or never enter REM sleep during hibernation. It’s almost as though the primate brain builds up a desperate need for REM-sleep during hibernation, Klopfer speculates, and satisfies the need with long REM sessions. As part of a recent study, scientists discovered that hibernating black bears maintain typical cycling between REM and non-REM sleep, but unlike many smaller hibernators their body temperatures do not drop all that much.

To Klopfer, the discrepancy between the sleeping patterns of hibernating ground squirrels and dwarf lemurs suggests that hibernation is not a conserved trait passed down from one evolutionary generation to the next. Rather, hibernation might be a convergent trait that evolved independently several times in different groups of animals. But studies on how fat-tailed dwarf lemurs hibernate are preliminary, Klopfer stresses, and—as with much hibernation research—there are still more questions than definitive answers.

Klopfer also thinks that, as a primate, the fat-tailed dwarf lemur is a better animal model than the arctic ground squirrel, hamster or hedgehog for studies on inducing hibernation in people. Some scientists have framed the possibility of deliberately reducing a person’s body temperature and metabolism in a controlled manner as a medical breakthrough that could permit otherwise impossible surgeries, as well as deep space travel. Although researchers have made some progress in artificially inducing hibernation in rodents, we are nowhere near ready to send human popsicles to Mars.

In about a week, Klopfer is returning to Madagascar to continue studying the fat-tailed dwarf lemur and to begin investigating the brain activity of the tenrec, which looks somewhat like a shrew and is the only other tropical mammal that hibernates. If the tenrec also enters REM sleep during hibernation, then this style of hibernation might be explained by a tropical environment, rather than a behavior unique to hibernating primates. Perhaps, Dausmann proposes, only the brains of tropical hibernators have the opportunity to get warm enough for REM sleep in an energetically efficient manner. An arctic ground squirrel hibernating in a burrow deep underground is not exposed to much fluctuation in ambient temperature, so it has to actively warm its brain in order to sleep, which requires a lot of energy—perhaps too much energy to fully enter REM sleep. A tropical hibernator, in contrast, could rely in part on high ambient temperatures to warm its brain enough for REM sleep.

Regardless of the exact details, the fact remains: fat-tailed dwarf lemurs are remarkable.  These tiny lemurs show that is is possible for a primate and its brain to survive off of nothing but a tail’s worth of fat for seven months—enduring large fluctuations in body temperature every day during that period—and to emerge from the whole experience, a little groggy perhaps, but as healthy as ever. Scientists now know where dwarf lemurs go when they disappear and what they are doing. Now they just have to figure out how they do it.

Chapter 4: What is the Ratio of Glia to Neurons in the Brain?

By Daisy Yuhas and Ferris Jabr

The green branches of an astrocyte, one of several kinds of glial cells, surrounded by blue nuclei of other cells (Credit: Karin Pierre, Institut de Physiologie, UNIL, Lausanne. via Wikimedia Commons)

Last time on Know Your Neurons, we talked about glia—one of two major types of cells in the brain and nervous system alongside neurons. Glia “outnumber neurons by as much as 50 to one,” we wrote, echoing Eric Kandel’s widely used textbook, The Principles of Neural Science, which states: “Glial cells far outnumber neurons—there are between 10 and 50 times more glia than neurons in the central nervous system of vertebrates.” Other textbooks, including Mark Bear’s Neuroscience—Exploring the Brain, make similar claims, as have many articles in the popular press.

Noah Gray (@noahWG), a senior editor at Nature, and Mo Costandi (@mocost), a neuroscientist turned freelance writer, responded to our post on Twitter, citing recent evidence that the 10:1 glia to neuron ratio is a myth and that the ratio in human and other primate brains is much closer to 1:1. We decided to investigate further.

After surveying the research literature, we did not find a single published study that directly supports a 10:1 glia to neuron ratio in the whole human brain. If anyone knows of such a study, please cite it in the comments section. We found many studies from as early as the 1950s that settled on a ratio much closer to 1:1 in the brains of humans and other primates, although most of these studies focused solely on the intricately wrinkled outer layer of the vertebrate brain, known as the cortex, which probably does not have the same glia to neuron ratio as the rest of the brain. The most compelling evidence for a 1:1 ratio comes from a 2009 study by neurophysiologist Suzana Herculano-Houzel and her colleagues, who invented a new, highly efficient way to count cells and applied it to four whole human brains.

Some researchers, however, will not fully accept the new method until Herculano-Houzel directly compares it to more traditional cell-counting techniques. And some scientists who study glia are reluctant to admit that these once overlooked cells might not constitute the majority. Even if Herculano-Houzel’s method somehow skews the ratio too close to 1:1, the evidence as a whole certainly does not support anything near a 10:1 ratio. Despite this discrepancy, some textbooks will likely continue to tout the 10:1 ratio as undisputed fact. Ben Barres of Stanford University is writing the sections on glia in the upcoming edition of Kandel’s textbook. Although he maintains that no one has rigorously determined the glia to neuron ratio in published research, he is convinced that glia make up at least 80 percent of the cells in the human brain—a conclusion he reached based on calculations about changing levels of DNA in the developing brain.

A selection of different types of glial cells. NG2s may be a new category (Credit: Daisy Yuhas)

The Available Evidence

Since at least the 1950s scientists have tried to estimate the relative number of neurons and glial cells in the human brain. They encountered difficulties right away.

The most rigorous method involves slicing up different regions of a fresh or preserved brain into thin sheets of brain prosciutto, counting cells in each sheet under a microscope and multiplying cell counts by total brain volume. The process is fairly straightforward but performing it on an entire brain takes a lot of time—even when computers and machines help with the counting—which explains why so many studies focus on only one region of the brain.

Early on, however, researchers realized that the ratio of glia to neurons varies from one brain region to another, sometimes dramatically. Several early studies found a glia to neuron ratio of about 1:1 in the cortex, for example, but one 1988 study found a glia to neuron ratio of 17 to 1 in the thalamus, a versatile pair of walnut-sized knobs near the middle of the brain. Further complicating things, the glia to neuron ratio differs from species to species. So counting the numbers of glia and neurons in a chunk of rat brain tissue does not give you an accurate estimate of the ratio for the whole rat brain, nor does it necessarily match the ratio in a comparable region of the human brain. Numerous cell-counting studies from the 1950s onwards concluded that the glia to neuron ratio in the primate cortex ranged from 0.5:1 to 2:1. As far as we can tell, none of these studies estimated a 10:1 glia to neuron ratio for either the cortex or the whole brain.

Neurons and glia in light-sensitive tissue at the back of a mouse's eye (Credit: Nakamura et al., BMC Cell Biology 2007, 8:52 doi 10.1186/1471-2121-8-52, via Wikimedia Commons)

If no published evidence directly supports the 10:1 glia to neuron ratio, how did it end up in so many textbooks? And where did the notion come from in the first place? “It’s impossible to find the original source,” says Claus Hilgetag of the University Medical Center Hamburg-Eppendorf, who has searched in vain for the basis of what he thinks is a long-perpetuated myth. One of his colleagues, Hugues Berry, vaguely remembers learning that the 10:1 ratio originated as a misremembered detail in a presentation at an academic conference. If so, it certainly would not be the first time that people have adopted a counterintuitive statistic as fact.

In a Brain Structure and Function column reviewing the relevant evidence on the brain’s glia to neuron ratio, Hilgetag and Helen Barbas of Boston University highlight the research of neurophysiologist Suzana Herculano-Houzel of the Instituto de Ciências Biomé́dicas/Federal University of Rio de Janeiro, Brazil. She has developed a unique, speedy method for counting all the cells in a whole brain.

Herculano-Houzel’s technique transforms an intact brain into a soup of nuclei—small sacks that contain cells’ DNA. The idea behind her method is that each brain cell contains exactly one nucleus; therefore, the total number of nuclei in a brain matches the total number of brain cells. First, Herculano-Houzel slices up an entire brain into regions of interest—such as the cerebellum and the cerebral cortex—and grinds up all the tissue by hand in a kind of glass mortar and pestle. Dissolving the tissue in saline detergent creates a solution in which the nuclei of both neurons and glia float freely. Tagging the DNA inside the nuclei with fluorescent proteins makes all the nuclei glow blue under ultraviolet (UV) light. Herculano-Houzel measures the density of these glowing nuclei and multiplies that number by the solution’s volume to determine the total number of nuclei, which should correspond to the total number of cells in that brain region. Next, she adds an antibody called anti-NeuN that binds to proteins on most neuronal nuclei, but does not bind to any glial nuclei. Another fluorescent antibody attaches to anti-NeuN, making nuclei from neurons glow green under UV light. After vigorously shaking the solution to evenly distribute nuclei from neurons and glia, Herculano-Houzel takes several samples of the soup, counts the fluorescing green nuclei in each sample under the microscope and calculates the total number of neuronal nuclei in the solution, which should equal the total number of neurons in that brain region. Subtracting that number from the total nuclei count tells her how many glial cells that section of brain contained.

Herculano-Houzel and her colleagues used this technique to analyze the brains of four deceased men and published their results in 2009: they consistently found a whole human brain glia to neuron ratio of almost exactly 1:1. Specifically, they found that the human brain contains about 170.68 billion cells, 86.1 billion of which are neurons and 84.6 billion of which are glial cells. Their study also suggests that the ratio of glia to neurons differs dramatically from one general brain region to the next. 60.84 billion cells in the cerebral cortex are glia, while only 16.34 billion cells are neurons, giving this large region a glia to neuron ratio of about 3.76 to 1. It’s the inverse in the cerebellum, an evolutionarily ancient part of the brain that sits astride the brain stem. According to Herculano-Houzel’s study, the cerebellum contains 69.03 billion neurons and only 16.04 glial cells, which means there are about 4.3 neurons for every glia in this region.

Adapted from "Equal Numbers of Neuronal and Nonneuronal Cells Make the Human Brain an Isometrically Scaled-Up Primate Brain"

Zooming in even further, her study counted 6.18 billion neurons and 8.68 billion glia in the gray matter of the cortex, vs. 1.29 billion neurons and 19.88 billion glia in the white matter. Gray matter is largely made up of the unmyelinated parts of neurons—neurons that are not sheathed by glial cells—whereas white matter is comprised of axons wrapped in insulating oligodendrocytes. These results might explain why so many early counting studies that only sampled cortical gray matter found a roughly 1:1 or slightly higher glia to neuron ratio. Overall the cerebral cortex—including both gray and white matter—contains far more glia than neurons, but its outermost gray layer is more balanced. And the cerebellum’s incredible density of neurons balances out the glia to neuron ration throughout the whole brain.

When Herculano-Houzel first published her innovative technique in 2005, the main objection was that she had not directly compared it to more typical stereological methods, in which cells are counted in slices of brain tissue. When her results with whole brains matched counts from different brain regions in previous stereological studies, however, Herculano-Houzel says most critics backed off. Some researchers remain concerned that grinding and dissolving the brain destroys a significant number of nuclei. Herculano explains, however, that the saline detergent she uses (Triton X-100) destroys fatty tissues, like cell membranes, but preserves the protein-rich nuclear membrane. Furthermore, she says, fixing brain tissue in formaldehyde before grinding strengthens the bonds between proteins, making them especially difficult to break. Other researchers say they are hesitant to trust a method that has not been widely used outside of a single research group. So far, however, at least seven different research teams in the U.S., Europe and Asia have availed themselves of Herculano-Houzel’s method.

Rewriting the Textbooks?

Human astrocyte stained with green fluorescent protein (Credit: Bruno Pascal, Wikimedia Commons)

Neurobiologist Ben Barres of Stanford University says he never believed the widely parroted 10:1 glia to neuron ratio—until he looked into the matter himself. Now, he is certain that glia make up at least 80 percent of cells in the human brain. Here is his main reasoning.

The human brain contains a finite number of cells, each of which holds the same amount of DNA (about 6.5 picograms). The developing human brain produces most of its neurons within the first trimester of pregnancy, but glia do not finish growing in number until a few years after birth. By comparing the total amount of DNA in a 20-week-old human brain to the total amount of DNA in an infant’s brain, Barres reasoned, one could figure out the glia to neuron ratio. Barres found a study published in 1973 that analyzed DNA levels in 139 human brains ranging in age from 10 weeks to seven years. The forebrains (which do not include the cerebellum) contained about 0.25 millimoles of DNA at week 20 and peaked at around 2 millimoles of DNA by age two. Based on these numbers—and accounting for DNA from blood vessel cells—Barres concludes that growing numbers of glia explain the increase in total forebrain DNA and that glia therefore make up at least 80 percent of cells in the human brain.

Even though Barres is confident in his own unpublished calculations—and intends to write that glia far outnumber neurons in the newest edition of the Principles of Neural Science—he argues that no one has conducted the kind of rigorous study that would definitively answer the question of the glia to neuron ratio once and for all. Barres envisions a study in which researchers stain whole human brains with just about every known marker for both neurons and glia—making sure to capture as many of the different cell types as possible—before slicing up the brains and meticulously counting the cells in each section. He says all the necessary tools are available. It is only a matter of funding the project and finding the time for all that counting.

Who Cares?

Let’s say scientists figure out exactly how many glia and neurons the brain contains and everyone agrees on the numbers—what will that accomplish? Why does it matter?

Neurons and glia in a mouse hippocampus (Credit: http://brainmaps.org, via Wikimedia Commons)

Some scientists think that the glia to neuron ratio is just about one of the least important questions you can ask about the brain. Instead, they argue, scientists should focus on how brain cells behave. Other scientists point out that aging, as well as many neurological diseases, involve the loss of brain cells. Understanding exactly which brain cells die and which survive could spur the development of new treatments. Some biologists and neuroscientists are also very interested in whether the glia to neuron ratio has changed over the course of evolution and whether, for example, animals with large brains—or brains that are large for their body size—have unusually high or low numbers of glia. In a 2007 study, scientists sliced up five minke whale brains, counted the cells with the help of computers and found 12.8 billion neurons surrounded by 98.2 billion glia. However, the study did not include the cerebellum, which contains most of the mammalian brain’s neurons according to Herculano-Houzel’s work.

Many researchers have argued that glia deserve more attention in part because they are so numerous. But prevalence is not equivalent to significance. Scientists no longer need to depend on the alleged 10:1 ratio to justify glia research. Glial cells are fascinating and important because of their structural diversity, functional versatility and the fact that they can change the behavior of firing neurons even though they cannot discharge electrical impulses of their own. They guide early brain development and keep their fellow brain cells healthy throughout life. Glia are not mere structural filler, but—as the origin of their name implies (Greek for glue)—they help keep things together. Regardless of the true glia to neuron ratio, scientists have already shown that glia are, functionally, the brain’s other half.

References

Azevedo, Frederico A.C. , Ludmila R.B. Carvalho, Lea T. Gribergb, José Marcelo Farfel, Renata E.L. Ferretti, Renata E.P. Leite, Wilson Jacob Filho, Roberto Lent, and Suzana Herculano-Houzel. “Equal Numbers of Neuronal and Nonneuronal Cells Make the Human Brain an Isometrically Scaled-Up Primate Brain.” The Journal of Comparative Neurology, 2009, 513:532-541.

Dobbing, J and Sands, J. Quantitative growth and development of human brain. Arch Dis Child. 1973 October; 48(10): 757–767.

Eriksen N, Pakkenberg B. Total neocortical cell number in the mysticete brain. Anat Rec (Hoboken). 2007 Jan;290(1):83-95.

Herculano-Houzel, Suzana and Roberto Lent. “Isotropic Fractionator: A Simple, Rapid Method for the Quantification of Total Cell and Neuron Numbers in the Brain.” The Journal of Neuroscience, 2005, 25(10): 2518-2521.

Hilgetag, Claus and Helen Barbas. “Are there ten times more glia than neurons in the brain?” Brain Structure Function, 2009, 213:365-366.

Kandel ER, Schwartz JH, Jessell TM 2000. Principles of Neural Science, 4th ed. McGraw-Hill, New York.

Pakkenberg, B. and Gundersen, H. J. G. (1988), Total number of neurons and glial cells in human brain nuclei estimated by the disector and the fractionator. Journal of Microscopy, 150: 1–20. doi: 10.1111/j.1365-2818.1988.tb04582.x

The Neurocritic. Fact or Fiction? There are ten times more glia than neurons in the brain. Sep 27, 2009.

Chapter 3: Know Your Neurons: Meet the Glia

*By Daisy Yuhas

A roundup of glial cells, inspired by the drawings of Pío del Río-Hortega, a student of Santiago Ramón y Cajal. Click to enlarge (Credit: Daisy Yuhas)

Trillions of cells in your brain communicate with one another, respond to infections, guide tissue development and support learning and memory—but none of these cells are neurons. These cells are known as glia and they outnumber neurons by as much as 50 to one (Edited to Add: More recent evidence suggests that the human brain’s glia to neuron ratio is much closer to 1:1. For a thorough discussion, see Chapter 4).

For most of history glia were simply, you know, the 85 percent of brain cells “leftover” when you looked for neurons. Researchers initially assumed that glial cells were just structural filler. Later, hints emerged that glia served as the neurons’ helpmate: housekeeper, insulator, occasional nurse. Today, scientists are starting to accept that the brain’s other half boasts a repertoire of functions every bit as vital as those of neurons.

Glia’s story begins in 1856 with Rudolf Virchow, a German biologist famed for his work in pathology and his dogged dismissal of Darwinism. While hunting for connective tissue in the brain, he identified “a sort of putty” studded with nerve cells. He christened this material nervenkitt in German, or neuroglia from the Greek for “nerve glue.” Ten years later, German anatomist Otto Karl Deiters identified some unusual cells amidst this sticky stuff. Because these cells lacked axons—the long slender cables that carry signals away from a neuron’s cell body—he surmised that these tailless cells were not neurons. As the century turned, researchers proposed different theories to explain these odd cells and their possible functions. Camillo Golgi used Dieters’s criteria to define glial cells, which he believed fed neurons. Santiago Ramón y Cajal posited that glia might be insulators for the electrical activity of neurons. What all descriptions of glial function had in common was the conviction that glia served as passive counterparts to the neurons’ active, central role in the brain.

It’s hard to fault this perspective. Staining techniques and early microscopes offered only a partial view into glia’s tiny world. Besides, neurons display all kinds of exciting electrical activity and glia do not. For a little insight into the perspective of these neuroscientists, imagine you’re at a crowded party. As you move through the room, your eyes are invariably drawn to the boisterous, talkative, and vibrant characters who seem to soak up the attention of everyone around them. In fact—and this is a little weird—with the exception of these characters, who only make up a scant 15 percent of the crowd, no one else at the party is talking. This is how neuroscientists understood brain cells for about a century: a few dazzling neurons, and then…glia, the silent, dull majority.

An astrocyte in culture. The green branches belong to the astrocyte and the blue are nuclei of other cells. (Credit: Karin Pierre, Institut de Physiologie, UNIL, Lausanne. via wikimedia commons)

By the early 20th century, however, scientists began to suspect that glia might be up to something. When they counted starry-shaped glial cells called astrocytes in various brains they noticed some peculiar patterns. For example, as Hungarian psychopathologist Ladislas von Meduna noted in the 1930s, individuals suffering from schizophrenia or severe depression had very few astrocytes in the cortex—the outer layer of the brain—while individuals who had experienced an epileptic seizure had an unusually high numbers (the observation inspired the development of electroconvulsive therapy). Fifty years later, neuroscientist Marian Diamond at the University of California Berkeley observed that although Albert Einstein’s neuron count and brain size seemed fairly average, his astrocyte count was well above average.

The strangest hint of all emerged in 1966, when Steven Kuffler and colleagues at Harvard exposed glial cells to charged potassium, one of the ions commonly released by neurons after firing. To their surprise, even though glial cells don’t have axons—which means they can’t carry and send an electric signal—exposure to charged ions still changed the glial cell’s charge, a shift very like the first step when a neuron fires. Here was definitive evidence that glial cells could ‘respond’ to a neuron’s signal.

The end of the twentieth century brought the biggest surprise. In a series of experiments conducted throughout the 1980s and 1990s, it became clear that instead of passive witnesses to neuronal activity, glia were actively involved in sending and receiving signals to neurons and other glia. When scientists exposed glial cell cultures to molecular messengers called neurotransmitters, the cells responded by taking in calcium. In 1990, Ann Cornell-Bell and Steven Finkbeiner at Yale documented how the influx of calcium in one glial cell led to a similar influx in neighboring glial cells, creating a wave of calcium uptake that spread across glia. Four years later, Maiken Nedergaard at New York Medical College observed that the calcium wave affected nearby neurons as well as glial cells. Not only do glia respond to a neuron’s chemical signals, they also produce their own chemical messages that influence the activity of neurons. In short, glia had been talking—to each other and to neurons—all along, but instead of communicating both electrically and chemically like neurons, they only communicated chemically.

It’s not idle chatter, either. “We now realize that glia are involved in every aspect of neuron function,” says neurobiologist R. Douglas Fields of the National Institutes of Health. “Glial cells are even more complicated than neurons and involved in many, many more processes.” Glial cells maintain the brain’s environment, regulate synapses and neurotransmitters, respond to injuries, and in certain cases can even become neurons.

Glial cells: First four from left represent the main glial groups. NG2s may be a new category. (Credit: Daisy Yuhas)

Here’s an introductory teaser to five types of glia researchers have discovered so far:

Astrocytes: The star-shaped astrocyte uses thousands of arms to take up neurotransmitters, cleaning up after neuronal activity. Scientists suspect that they’re the most common type of glial cell in the brain, and some believe that the calcium waves astrocytes generate may underlie creative thought.

Oligodendrocytes: The octopus-like oligodendrocyte wraps the tips of its tentacles around axons in a fatty white coating called myelin. Studying such ‘white matter’ may provide insights into intelligence and learning and problems with myelin are at the heart of diseases such as multiple sclerosis.

Schwann cells: Much like an oligodendrocyte’s protective tentacles, Schwann cells form a snug layer of myelin around the axon like the bread around a corn dog. As the only glial cell in the peripheral nervous system—the nerves outside the brain and spinal cord—Schwann cells adopt a range of different roles, including astrocyte-like chemical clean ups.

Microglia: While the previous three cells belong to a category called macroglia, there are also smaller microglia. These wee cells are the brain’s rapid response team. Since the immune system’s molecular machines can’t cross the blood-brain barrier, the versatile microglia defend the brain from invaders.

NG2 Cells: Their name may not be that memorable, but NG2s—or the cell previously known as “oligodendrocyte precursor cells“—are big news in the world of glia research and may even constitute a whole new category of macroglia. These cells transform not only into different kinds of glia, such as oligodendrocytes and astrocytes, but also into neurons, further blurring the lines that distinguish the two types of cells.

*Daisy Yuhas is a science writer based in New York and an intern with Scientific American MIND

References

Somjen, George S. “Nervenkitt: Notes on the History of the Concept of Neuroglia.” Glia 1:2-9 (1988).
Fields, R. Douglas, and B. Stevens-Graham. “New Insights into Neuron-Glia Communication.” Science 298:556-562 (2002).
Verkhratsky, A. and A. Butt. “Introduction to Glia.” Glia Neurobiology: A Textbook. John Wiley & Sons, Ltd. 2007.
“History of Glia.” Neur 1930E: Great Controversies in Neurobiology. Brown University (course site.)
Jessen, K. R. “Glial cells.” The International Journal of Biochemistry & Cell Biology. 36: 1861-1867 (2004).
Perry, S. “Glia: the Other Brain Cells.” BrainFacts.Org. 2010.
Patoine, B. “Rethinking the Synapse: Emerging Science Challenges Old Assumptions.” The Dana Review. 2005

Additional reading

Fields, Douglas. “The Other Half.” Scientific American. April 2004.0
Fields, Douglas. “The Hidden Brain.” Scientific American MIND. May/June 2011.
Koob, Andrew. “The Root of Thought: What do Glial Cells Do?” Scientific American online.  October 27, 2009.
Leitzell, Katherine. “The Other Brain Cells: New Roles for Glia.” Scientific American MIND. June 2008.
Zimmer, Carl. “The Dark Matter of the Human Brain.” Discover Magazine. September 2009.