children-video-game

Gamification of Science: Making Science Fun

The Video Gamers United recently convened in Washington DC. As I glanced at its imposing, back-lit poster decking the otherwise drab walls of the metro station on my way to work, I started thinking about science-based video games and their impact on science education. It turns out, science-based video gaming is a flourishing field, with numerous games being developed for the purposes of edutainment and advancement of science: EteRNA, FoldIt, Genomics Digital Lab, History of Biology game, Phylo, and Nanomission to name a few. These video games are designed to solve complex scientific problems, develop interest in the area, and serve as a tool for learning. The question is: Do they work?

Several science games take advantage of citizen science by crowdsourcing complex scientific challenges sometimes too hairy for even advanced computer programs. The idea is that many minds together can solve a complex problem better than one mind or one machine alone. Stemming from this principle of game with a purpose is EteRNA, a puzzle-based game that enables development of new designs of RNA molecules by the gaming community. Created by researchers at the Carnegie Mellon University and Stanford University in 2010, the game allows players to contribute to a large scale library of RNA designs, helping reveal “new principles for designing RNA-based switches and nanomachines– — new systems for seeking and eventually controlling living cells and disease-causing viruses.” Interestingly, playing the game does not require any training in biology.  EteRNA is considered a successful project, with over 150,000 players engaged in designing novel RNA molecules to be used in real-life research.

Another crowdsourced game Phylo, designed to augment genetic disease research, looks a lot like the classic Tetris at first glance. Players are asked to align blocks of similar colors. Unbeknownst to many players, the blocks represent gene sequences from different species. The better a player does at matching the sequences the more points she accrues.  The computer programs designed for doing this type of multiple sequence alignment do not necessarily produce superior results, often requiring scientists to manually align some sequences to attain the most appropriate alignment. This is where the Phylo players come in. More than 300,000 people have played Phylo since its launch in 2010.

Another big motivation for developing science-based video games is helping players develop an interest in science. The History of Biology is a good example. Designed by Spongelab Interactive, the game follows a scavenger hunt format, where players solve a mystery based on clues illustrating seminal discoveries in the world of scientific research. Spongelab Interactive is a major developer of several other educational games, covering a wide-range of subjects such as chemistry, physics, mathematics, and history.

Many video games are also built as tools for learning. The idea is to use a cultural tool, something that students of a particular culture respond to, aka video games, to enable learning in a familiar and friendly format (see article by Morris et al, 2013). Students learn the process of scientific thinking as well as key concepts in a self-paced environment, where learning is assessed by ability to overcome increasingly difficult levels, and rewarded through a feeling of achievement. NanoMission is an educational game, with the goal to teach players about the up and coming field of nanotechnology. Through multiple modules of the game, players engage in a variety of stimulating activities, such as guiding a nanorobot in killing cancer cells in a patient; or creating improved nanomedicine or nanomachines; or destroying harmful algae.

While video games can help in accomplishing all of the above, an important criterion for judging their potency is assessing the accuracy of the science they represent. Caution must be taken when facts are misrepresented in an attempt to make the game interesting or technically feasible. Reinforcing inaccurate concepts about science can not only be ineffective in generating interest and increasing knowledge, but also detrimental to the overall learning experience of the player (see review of Spore by John Bohannon).

Though gradually gaining popularity, gamified science, so to speak, has yet to become integrated into the vast world of conventional video games. Hinting towards a positive future, however, is the fact that the Washington DC Video Gamers United Convention featured several keynote speakers specializing in serious games, including Christopher Spivey, Sande Chen, and Trey Reyher- an excellent move for science gamification.

One Thousand Self-Organizing Robots Emulate Elements in Nature

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A few months ago, in a desperate attempt to save time in cleaning up after an active toddler, we bought the Roomba iRobot, an automated vacuum cleaner. The awe we felt from watching the Roomba pick up hair and Cheerios under the bed must have been the same awe that man felt after inventing fire. A hands-free, self-guided, self-charging machine doing our dirty work: now that’s technology! As the Roomba did its thing, my husband and I imagined a time when the big Roomba would come with little baby Roombas that would spawn from its base, and reach inaccessible turfs like the corners of the walls, curtains, or window sills, clean-up, and go back to base to charge with mama Roomba.

That time seems quite upon us, with the invention of the thousand self-organizing robots by Harvard researchers, Michael Rubenstein, Alejandro Cornejo, Radhika Nagpal, published today in Science. The behavior of these robots emulates similar elements in nature, such as self-organizing ants and termites that practice meticulous coordination to achieve complex tasks. This adds to the myriad technological advances stemming from a basic understanding of biological life. Self-organization is a behavior seen throughout nature: in bees, ants, birds, and even bacteria. In fact, the bacterium I studied for my doctoral work, Myxococcus xanthus, is a remarkable species, capable of self-organizing via chemical communication with members of its colony to accomplish motility and predation on bacteria of other species. The Kilobots, as the researchers call their army of thousand robots, perceive each other through the transmission and reception of infrared signals from their bases, to independently self-organize into complex shapes from stars to the letter K.

And what could these Kilobots be useful for? A variety of applications come to mind, from cleaning up chemical spills to environmental surveillance for pathogens, to digging for mines, and, most importantly, cleaning up the corners of your house!

The only thing now left to do is to give these Kilobots a cute body. I wonder if Wall-E is available!

New protein may be the Achilles’s Heel of Treatment-Resistant Head and Neck Cancer

The human Head by Leonardo Da Vinci

The human Head by Leonardo Da Vinci

Researchers at the University of Michigan, Ann Arbor believe they have solved the mystery behind why some head and neck cancer cells are refractory to the effects of radiation and chemotherapy and extremely adept at repairing and thriving under such aggressive insults. According to the findings of a new study from the group of Dr. Nisha J D’Silva that appeared in Nature Communications this week, a protein named TRIP-13 is responsible for enabling cancer cells to repair their damaged DNA using a process called error-prone non-homologous end joining. Using recombinant DNA technology, the group also showed that normal cells could be transformed into malignant cancer cells by overexpression of TRIP-13.

Head and neck cancer is one of the most common cancers in the world, and often afflicts users of tobacco and alcohol, as well as people infected with the Human Papillomavirus (HPV). The malignancy often starts in the squamous cells lining the moist surfaces of the head and neck, and can quickly spread through most of the oral cavity. Adding to its severity is the fact that the cancer is notoriously resistant to treatment and comes with a high recurrence rate.

Dr. D’Silva’s research findings offer a plausible explanation for such a high recurrence rate and overall intractability of head and neck cancer. Adding to the hope is the group’s  identification of an existing molecule potent in killing these TRIP-13-expressing cells, offering a direct and potentially speedy treatment option for the near future.

Five Inspirational Non-Fiction Books by Physician-Writers You Won’t Want To Put Down

  1. Becoming Dr. Q: My Journey from Migrant Farm Worker to Brain Surgeon

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In this spellbinding memoir, Dr. Q, short for Alfredo Quinones-Hinojosa, reveals his tumultuous, yet exciting journey, from his impoverished childhood in Mexico, to literally jumping the fence to enter the United States, to farming tomatoes for pennies under the unforgiving California sun, while also taking evening English classes, to graduating from Harvard Medical School, and finally becoming an internationally celebrated neurosurgeon and cancer researcher at the Johns Hopkins University. Dr. Q’s descriptions of his brushes with death are both gripping and uplifting, and his life is the American Dream personified.

  1. The Emperor of All Maladies: A Biography of Cancer

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Dr. Siddhartha Mukherjee elegantly and effortlessly breaks it down for his readers, connecting the present with the past of cancer origins and the evolution of its treatment. Thorough, yet succinct, Dr. Mukherjee’s writing recounts the key events and figures that fundamentally changed the way we look at cancer today. After reading this biography of cancer, you will come out feeling educated and optimistic. A must read for anyone curious about the past, present, and future of this age-old disease.

  1. Mountains Beyond Mountains

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Although not exactly written by a Physician-Writer, the book covers the life of an amazing and inspiring infectious disease specialist, Dr. Paul Famer, who is also a professor of medical anthropology at Harvard and the recipient of the MacArthur Genius Grant. In this biography of Dr. Farmer, author Tracy Kidder takes the reader to Haiti, where Dr. Farmer is literally working day and night to treat patients in a remotely-situated Haitian village. The book highlights Farmer’s unyielding efforts to improve the health of marginalized people, culminating in the founding of Partners in Health, in collaboration with his long time friend, Jim Yong Kim, who recently served as the president of the World Bank. By following Farmer around, Kidder captures how on more than one occasion, Farmer puts his patients’ needs before his own health, money, family, safety and even life. Kidder’s Mountains Beyond Mountains highlights the best humanity has to offer. A great read for anyone looking to feel motivated and inspired.

  1. Gifted Hands

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Is the autobiography of the renowned Dr. Benjamin Carson, the first neurosurgeon in the world to successfully separate conjoined twins. A gripping narration of personal and professional challenges, the autobiography illustrates the victory of hard-work and determination over the many hurdles of poverty and discrimination that Dr. Carson faced as an African American child, growing up in a disadvantaged neighborhood of Detriot, Michigan, or even as a doctor, having his credibility repeatedly questioned by colleagues and patients alike. As a bonus, Dr. Carson skillfully describes several groundbreaking surgeries he pioneered in his fertile career as a neurosurgeon.

  1. When the Air Hits the Brain

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This riveting memoir by Dr. Frank Vertosick Jr. presents some of the most challenging cases of his medical career as a neurosurgeon. Dr. Vertosick consciously chooses to narrate the cases with rather unhappy endings and contends that one learns more from failures than from successes, especially in surgery. The book is often recommended for medical students, but is also relevant to anyone interested in learning how doctors make some very difficult, life or death choices.

 

 

Two new studies on oral bacterium that causes lethal heart valve infection

Originally published in (ASBMB Today)

S. sanguinis
False-colored transmission electron micrograph of Streptococcus sanguinis cells (purple ovals) encased within an infected heart valve in an animal model of infective endocarditis. Mutants lacking either the NrdEF ribonucleotide reductase or the NrdI protein required for manganese cofactor formation were unable to cause disease. Click on the image to see a larger version of it.

Two back-to-back studies published in The Journal of Biological Chemistry have provided significant insights into virulence of Streptococcus sanguinis, which causes a potentially lethal infection of heart valves.

Infective endocarditis occurs when the otherwise innocuous S. sanguinis, a Gram-positive, facultative aerobic, oral bacterium, enters the blood stream and colonizes vulnerable heart valves or endocardial tissue, an infection that proves to be lethal for more than 20 percent of patients. The severity of this disease and the lack of a vaccine for it make it imperative to understand the mechanism of virulence by S. sanguinis to facilitate the development of potent antimicrobial agents.

The studies in the JBC resulted from a collaboration between the labs led by Todd Kitten at Virginia Commonwealth University and JoAnne Stubbe at the Massachusetts Institute of Technology.

Two past observations prompted the research teams to examine the activity of the bacterium’s class Ib ribonucleotide reductase, or RNR. These essential enzymes rely on metallo-cofactors to convert ribonucleotides into deoxyribonucleotides, precursors for DNA replication and repair. In S. sanguinis, RNRs occur in two forms: the aerobic class Ib and the anaerobic class III.

The first observation was that deletion of a manganese transporter called SsaB drastically reduces the virulence of S. sanguinis and its ability to tolerate oxygen. So the researchers set out to “identify manganese-requiring proteins that would also be required for growth in oxygen,” explains Kitten. The second observation was that class Ib RNRs, along with an iron cofactor, also appear to employ a dimanganese-tyrosyl radical cofactor for in-vivo activity. “We wondered whether the oxygen-dependent class Ib RNR might be the manganese-requiring enzyme we were seeking,” Kitten says.

In the first study, the researchers demonstrated that the S. sanguinis RNR can not only self-assemble a diferric-tyrosyl radical in the presence of oxygen, but also assemble a dimanganese-tyrosyl radical, if provided with an additional enzyme called NrdI.

Todd Kitten
Kitten
Joanne Stubbe
Stubbe

“In my view, the main contribution of the first study was that it identified all the components and established that the S. sanguinis RNR had the properties that were expected of it,” says Kitten. “We confirmed that RNRs behaved the way we thought they would in vitro, and we provided direct evidence about which components are required for RNR activity.”

Emboldened by those findings, the researchers in the second study created mutant strains of S. sanguinis lacking class Ib RNR or other RNR-related enzymes and tested those mutants for growth competency under aerobic and anaerobic conditions.

The authors reported that the mutants lacking the genes for synthesis of class Ib RNRs or the manganese cofactor were unable to grow aerobically (but grew normally under anaerobic conditions) or cause endocarditis in a rabbit model system. This phenotype, however, could be partially rescued by heterologous complementation with a class II RNR gene, which codes for an oxygen-independent, adenosylcobalamin-cofactored RNR.

These results allowed the authors to conclude that manganese was indeed critical for the proper function of RNRs and, consequently, for the virulence of S. sanguinis.

The work is significant because the results provide a novel target — manganese cofactored RNRs — for developing antimicrobial agents designed to treat infective endocarditis, and that is made even more promising by the fact that such RNRs do not exist in eukaryotes. The results also may answer the longstanding question of why some bacteria require manganese for oxygen tolerance and virulence.

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Nature’s Tea Lights: How Bioluminescent Organisms are Brightening Our Present and Our Future

It is summer time again and nature’s little tea lights-the fireflies- can be spotted everywhere. Many of us have fond memories of collecting them in a jar to make a lantern and awing at their glow.

Bioluminescent organisms produce light as a result of a reaction of a specific chemical with oxygen in the presence of a dedicated molecular catalyst, or enzyme. A vast variety of organisms exhibit this phenomenon, including insects, flies, fungi, snails, worms, and even microorganisms like dinoflagellates and bacteria. While many of these organisms can be found on land, most live in the ocean, where in the deep, dark waters, a little light can take them quite far. These incredible animals use their light to attract mates, communicate danger or other signals to their kin, startle, intimidate, and even fight predators.

Through decades of research on this fascinating phenomenon, scientists have achieved an impressive understanding of the key players involved in the production of light in a variety of bioluminescent organisms. The generated knowledge is now being applied to solve rather complex challenges facing biomedical research aimed at drug discovery as well as the development and treatment of cancer.

The application is called bioluminescence imaging (BLI), and is based on a simple idea: Use recombinant DNA technology to produce target cells expressing bioluminescence-effecting enzymes, provide the chemical substrate, and track target cells in a live animal by imaging the production of light.

The uses of this non-invasive technology are innumerable. For example, human brain tumor cells can be genetically modified to express firefly luciferase, the enzyme responsible for catalyzing the production of light by luciferin (the chemical), transplanted into mice brain, and visualized using a specialized camera upon deliverance of luciferin. The resulting light signals the presence of tumor cells. Using this study design, scientists can assess the effect of various chemotherapy drugs on the size of the tumor, and determine parameters such as dosage and efficacy of the drugs, and the time a particular drug takes to stall a neoplastic growth.

BLI is also tackling metastasis, or the spread of cancer from one part of the body to the other. Luciferase-expressing tumor cells can be injected in the tail veins of mice and their migration tracked by following the emission of light from the body of the mice. Another exciting avenue is exploiting the ability of bacteria to preferentially colonize tumor cells by injecting specially engineered bioluminescent bacteria into mice models of cancer to track the presence of cancerous lesions in the mice. Scientists hope that these bacteria can be engineered to serve as targeted drug delivery vehicles to the site of cancer lesions, to prevent damage to bystander cells, as is often the side-effect of chemotherapy. Other areas of application include “cell signaling, transcriptional promoters, gene expression, protein-protein interactions” and many more.

As with any technology, BLI has its limitations and drawbacks. Thus, efforts are being made every day to improve the technology by engineering enzymes with longer half-lives and better stability, more sensitive detection methods, and efficient experimentation techniques.

One of the basic challenges with biomedical research is differentiating a cell or tissue of interest from the rest. Visualization offers a viable solution. Being able to differentially visualize the cell or tissue of interest can allow one to make targeted interventions. It’s like walking in a room and having a specific switch to only turn on the light of a lamp in one of the many rooms with many lamps of a mansion- a complex task, simplified elegantly by the promise of BLI.

 

Works Cited:

Ruxana T. Sadikot and Timothy S. Blackwell. Bioluminescent Imaging. Proc Am Thorac Soc. Dec 2005; 2(6): 537–540.

Badr CE. Bioluminescence Imaging: Basics and Practical Limitations. Methods Mol Biol. 2014;1098:1-18

Haddock SHMoline MACase JF. Bioluminescence in the Sea. Ann Rev Mar Sci. 2010;2:443-93

Haddock, S.H.D.; McDougall, C.M.; Case, J.F. “The Bioluminescence Web Page”, http://lifesci.ucsb.edu/~biolum/ (created 1997; updated 2011; accessed 06/27/14).

Exquisite Scientific Art at Dulles International Airport

Image of a brain showing hallmarks of Alzheimer's disease by Alvin Gogineni, Genentech

Image of a brain showing hallmarks of Alzheimer’s disease (blue) by Alvin Gogineni, Genentech

I had just landed at the Dulles International Airport after flying non-stop for five hours from the Pacific to the Eastern Time zone, with a fussy toddler in my lap. It was two in the morning. Tired, hungry, and hauling about five different types of luggage, including a Hummer of a stroller, I was not feeling particularly up beat.

Yet, as I walked through the brightly lit passage on my way to the baggage claim, I was pleasantly struck by the sight of something very familiar adorning the otherwise bare walls- exquisite backlit microscopic images of biological cells and tissues.  Suddenly, I was at an art gallery, except that the images were authentic scientific data produced as a result of cutting edge biomedical research by scientists all over. Awe-inspiring pictures capturing the dynamic biological world, not visible to the naked eye, of mitotic cells with dividing DNA, viruses, the brain tissue and bacteria made me stop and take a look.

Life: Magnified,” is a result of a collaboration between the NIH’s Institute of General Medical Sciences, the American Society for Cell Biology, and the Metropolitan Washington Airports Authority’s Arts Program, and entails a display of 46 eclectic photographs selected from over 600 submissions by prominent researchers.

These images up till now have mostly been exclusive, often appearing in scientific journals or conferences, not readily accessible to laymen. By displaying the images at a venue which sees millions of passengers every year, the airport is contributing to the important task of increasing public awareness of the strides made everyday by researchers in solving the big questions facing us, including discovering cures to devastating diseases. Moreover, the images will inspire curious individuals to enter the world of scientific research. But most importantly, they provide a much-needed boost to fatigued travelers by reminding them of the beauty in the tiny things that surround us.

Mondrian_Composition_II_in_Red,_Blue,_and_Yellow

What’s the point of art?

If I ever win the lottery, I will fill my place with classic paintings by my favorite artists-Rembrandt, Vermeer, Monet, Titian- a dreamy aspiration shared by many around the globe. A fortunate few, and I mean both figuratively and literally, are actually able to realize this dream. In fact, some of the world’s most valuable art is owned by such moguls, like the famous Paul Cézanne painting The Card Players, sold to the Royal Family of Qatar at a jaw-dropping cost of $250 million to $300 million, or artist Willem Kooning’s Woman III, purchased by the American Hedge Fund manager, Steven Cohen, for an astounding $137.5 million, or Francis Bacon’s Triptych, bought by the Russian billionaire Roman Abramovich for $86.4 million. Even the fictional magnate Gail Wynard from The Fountainhead had his very own walk-in gallery of exquisite art right in his home- his authentic refuge from an artificial world.

Aside from the obvious monetary and investment values of these paintings, there is a more intangible value to art, almost spiritual in nature that unites us all. People from all socio-economic backgrounds, ages, nationalities, spend hours appreciating, creating, buying, discussing, and promoting art. Governments dedicate time and resources on setting up departments of art and culture, aimed at promoting and protecting art (sadly even destroying art incompatible with their ideologies). In fact, some of a child’s first modes of communication include not words, but art in the form of colors, drawings, objects, songs. Moreover, studying art alone can potentially reveal the entire history and evolution of mankind; from the first cave paintings in Spain etched on rock 40,000 years ago, to Rembrandt’s Anatomy lesson of Dr. Nicolaes Tulp from 1632, to the contemporary Obama murals by anonymous artists, adorning the dilapidated walls of Brooklyn.

Could the experience of looking at art be similar to meditation? A chance to be alone with your mind, a moment for introspection, to focus on just one thing—not on the echoing of Om– but on the vivid colors and textures of a painting, or the intricate carvings on a delicate porcelain vase– and channel your senses in a single direction to experience one’s own version of peace, love, or pleasure. Several scientific studies have used modern techniques such as functional magnetic resonance imaging (fMRI) (a technique that measures brain activity based on corresponding changes in blood flow) of the brain to reveal temporary and permanent effects from meditation on the brain. Do similar effects occur through thorough imbuement of the brain by art?

Other scientifically interesting questions arising from this prevalent and timeless phenomenon of art are: How does the brain process art? What about art gives us pleasure worth spending our limited time and money? In short, why do we, as a species, look at art? Is it because other, seemingly knowledgeable experts tell us that it’s something worth looking at? Would Van Gogh’s vase of twelve sunflowers be just an ordinary painting if it didn’t come with the brand name? Or do we just like looking at beautiful things (although plenty of famous art isn’t exactly beautiful)?

This fundamental human behavior has given rise to a burgeoning discipline of neuroscience: neuroaesthetics: a discipline dedicated to understanding the neurological basis of aesthetic experiences,

Using modern techniques and tools, scientists are working to understand why and how we look at art. For example, fMRI techniques can be used to determine the ways our brain activity changes in response to looking at art. Van Gogh’s paintings, as one study shows, activate the MT+ region of the brain (responsible for deciphering object locations), evoking a sense of movement in the viewer. Another study reveals that facial portraits activate a different region of the brain, when compared to landscape paintings. Moreover, beautiful faces activate the fusiform face region (responsible for facial recognition) and its adjacent areas, a neural activity that seems to increase with the beauty of an art piece*.

Neuroaesthetics studies have also provided insights into factors that influence our perception of art. For example, when labeled as belonging to a museum, an art piece receives better rating by its viewers, and greater neural activity is observed in certain areas of their brains. Moreover, different areas of the brain are activated in response to viewing an original masterpiece, or a copy* .

Another intriguing area of investigation is understanding the paradox of how certain neurological diseases enhance the artistic capabilities of patients, often allowing them to produce “realistic, obsessive, and detailed” art. Interestingly, some autistic individuals, given their characteristic obsessive-compulsive traits, are also predisposed to producing amazing art*.

It seems that when it comes to appreciating art, or even producing it, we rely on a combination of our built-in biology, as well as the experiences and environmental cues that influence our everyday experiences from the moment we are born. Thus, understanding why we look at art, can potentially enhance our understanding of complex concepts concerning human behavior, such as “mate selection, consumer behavior, and communication*.” Because even a mere still life can set into motion a surge of activity in the intricate neural circuitry of our complex brains.

*Chatterjee and Vartanian (2014) Trends in Cognitive Science

Narcissus-Caravaggio_(1594-96)_edited

Facing recession in early adulthood can prevent narcissism later in life

Finding a job is a humbling experience. As I go through the motions of a job search-applying, interviewing, networking- I find myself, inadvertently riding a roller coaster, precariously seated on the tracks of fickle emotions-confidence, self-doubt, poise, jubilation, and desperation.  Fortunately, once in a while,  I get a bolstering call or an email that offers me a positive direction or a much-needed nudge to stay strong to realize my unconventional career goals and interests.

In an economic recession, however, such a nudge is infrequent, or even non-existent, and the hardest hit are the young adults entering the workforce for the first time. A dearth of jobs enables employers to be selective and to only extend offers to highly skilled and experienced individuals, leaving young adults with limited to zero choices. The experience has a long-lasting effect on the psychology of these impressionable individuals, according to the results of a recent study by Emily Binachi at the Emory University.

Binachi started out by asking a reasonable question. “Does entering adulthood during a recession affect how narcissistic a person ultimately becomes? Narcissists regard themselves as superior to other people and believe that they are entitled to good outcomes, excessive admiration, and unyielding praise.”

To answer her question, Binachi surveyed thousands of individuals, asking them a variety of questions aimed at scientifically quantifying their level of narcissism, self-esteem, and economic conditions in emerging adulthood.

Binachi found that “entering adulthood during a recession tempered narcissism later in life, ” and the affected individuals were less likely to feel superior or entitled, related to others. Binachi also found that higher unemployment rates during emerging adulthood were associated with lower narcissism scores later in life, while economic conditions in the subsequent period were not as predictive of current narcissism. Most interesting was Binachi’s finding that CEOs of various companies who came of age in economic recessions paid themselves relatively less than those who entered adulthood in more prosperous times.

The results of Binachi’s studies offer a plausible explanation for the presence of narcissism in certain individuals. Other identified sources of such behavior include overindulgent and overprotective parenting and excessive and unearned praise during childhood. Personally, her study offers me a fresh perspective on my own job search- an opportunity in character building!