Let's Talk Bird Brains

Zachary Johnson

Originally published April 3, 2015

 photo by: kristen thomas

photo by: kristen thomas

For a long time we thought that language separated us from other animals, but it’s a bit more complicated than that. Chimpanzees, bonobos, gorillas, and orangutans can all learn sign language. Dogs can use body language, vocalizations, and even facial expression to communicate; and many birds can sing extraordinarily intricate songs to relay information. Even insects and plants can release chemicals that carry important information to their neighbors. So what’s unique about language?

While many animals can “speak,” or produce sounds, humans are uncommon because we can imitate sounds and mix and match them in new combinations to communicate information. This process is called “vocal learning,” and it requires using our vocal chords to imitate sounds. Neuroscientists believe we can do this because we have unique connections in our brains between higher processing areas at the front and motor areas further back that control our vocal chords; other primates—which can’t do vocal learning—don’t have these connections. But humans aren’t the only vocal learning animals, and scientists have turned their attention across 300 million years of evolution to learn more about this unique capacity.

While many birds can sing, their songs are often innate and fixed. Only three lineages possess the unique ability to learn, imitate, and modify their vocalizations based on what they hear: parrots, hummingbirds, and songbirds. Neuroscientists discovered that, like humans, these birds also have unique connections between frontal areas and motor areas controlling the vocal chords. These connections are absent in birds that can’t do vocal learning, like chickens. Both humans and vocal-learning birds that suffer damage to these connections have trouble imitating others’ vocalizations and stringing syllables together correctly. These discoveries had scientists scratching their heads: not only can distantly related birds do vocal learning, but their brains seem to be doing it in a similar way.

 photo by: kristen thomas

photo by: kristen thomas

Before diving deeper, it’s important to appreciate the explosion in technological capacity that biological research has witnessed in the past few decades. In 1950, we didn’t know what DNA was. Since then we’ve learned that the genetic codes, or “genomes,” of both humans and birds are made of billions of nucleotides (the building blocks of DNA). We know that every cell in the body contains the same genetic code, but specific kinds of cells turn parts of the genome “on” or “off,” depending on their jobs. Think of pianos; they all have the same 88 keys, but pressing those keys in different combinations and to different degrees results in different chords. Different types of cells in our bodies “express” different combinations of genes and to different degrees; each type has its own “chord,” or its own unique gene expression fingerprint. This is even true across species: gene expression fingerprints of skin, heart, and brain cells in humans may look different from each other, but they look very similar to gene expression fingerprints of skin, heart, and brain cells in other animals.

A team of Duke neuroscientists led by Dr. Erich Jarvis recently took these ideas a bit further: are the gene expression fingerprints of “vocal-learning” brain cells unique? In other words, maybe the animal genetic code can express certain genes to create vocal-learning brain cells across species, just like skin cells or heart cells. The scientists collected tiny samples of bird brain tissue from vocal-learning brain areas in parrots, hummingbirds, and songbirds and analyzed the gene expression fingerprints for each. Next, they tapped into a huge database of gene expression fingerprints spanning the entire human brain. Like forensic detectives, they searched the database for matches. Sure enough, the strongest matches in the human brain database were regions involved in human speech and language.

 photo by: kristen thomas

photo by: kristen thomas

So what? The idea here is that perhaps we aren’t quite as unique as we’d like to think. Scientists have known for a while that the genes guiding human body development are the same exact genes guiding body development across fishes, amphibians, reptiles, and birds. The Duke neuroscientists extended that idea to specific capacities of the human brain. The same genes that guide the development and wiring of areas involved in human vocal learning also guide the development and wiring of areas controlling vocal learning in birds.

It’s important because our language capacity is a huge part of being human, and it has indisputably shaped the course of our history. As biology advances, we will certainly continue to learn more about this unique capacity from parrots, hummingbirds, and songbirds, as well as our other vocal-learning relatives: bats, seals, elephants, and dolphins. In the meantime, the next time someone calls you “bird brain,” consider it a compliment, and take a moment to wonder what other capacities of the human brain and mind might be hidden in the animal genetic code.

Edited by: Bethany Wilson

The Mystery of Alzheimer’s: is it an Autoimmune Disorder?

Kevin Sullivan

Originally published April 2, 2015

 photo by: kristen thomas

photo by: kristen thomas

There is a good chance that you personally know someone suffering from Alzheimer’s disease. This is unsurprising, as it is estimated that one out of every nine people over 65 is affected, making it the most common form of dementia. Initially, someone with Alzheimer’s will show signs of forgetfulness and disorientation which may not be immediately noticeable. A person might find themselves losing their keys more often or asking the same question multiple times in a conversation without realizing it. These symptoms gradually get worse over a period of three to nine years, leading to more severe memory loss, mental and physical impairment, and eventually resulting in death. According to the 2014 World Alzheimer Report, 44 million people are living with dementia worldwide, with the number set to double by 2030. Aside from the devastating emotional costs imposed upon the individuals and their care providers, usually family members, the economic impact of dementia is an imposing figure. In 2010, the cost of care for dementia was $604 billion, with costs expected to exceed $1 trillion by 2030.

Decades of research have revealed several risk factors for the disease, such as age, head trauma, heart disease, and sex (women may be more susceptible than men). Despite information about these risk factors and studies revealing the differences between the brains of people with Alzheimer’s relative to those of healthy people, the exact cause still remains a mystery. In recent years, researchers have discovered many clues that have gotten us closer to solving this mystery. One of the key findings is that the degeneration of the brain in Alzheimer’s is associated with the presence of protein fragments called amyloid beta peptides. Amyloid beta is present in healthy brains as well, but problems arise in Alzheimer’s when these peptides become folded in an incorrect way, causing them to associate with one another and form clumps, called plaques, which deposit in the brain.

Another major finding is that tau proteins, which normally help to stabilize the structural components of cells, can become defective in Alzheimer’s disease, causing them to get tangled up and deposit in the brain. Both amyloid beta plaques and tau protein tangles are quite toxic to nerve cells and eventually result in the death of the neurons that make up the brain. Despite these and a variety of other clues that have been discovered, Alzheimer’s is plagued by the classic chicken-or-egg question: which of the observed problems are causes of the disease, and which ones are a result of the disease process? So far, this question has been very difficult to answer. Only one form of Alzheimer’s, known as early onset familial Alzheimer’s disease, has a definite cause involving a mutation in specific genes that produce amyloid beta proteins. However, these mutations are the cause of only 1 to 5 percent of cases, while the origin of the rest of the cases remains unclear.

The field of Alzheimer’s research is rapidly advancing, with new discoveries made nearly every day. One intriguing recent discovery suggests that an immune response may be responsible for the progression of Alzheimer’s disease. In a March 2015 review published in Nature Immunology, a group led by Michael T. Heneka from the University of Bonn explained some of these recent findings. One of these hypotheses proposed explains that, because amyloid beta is found in several different viruses and bacteria, the body developed an immune system response to the peptide in order to fight off these pathogens. In some cases, the immune response can become misdirected and targets the amyloid beta found in human tissue instead of that of an invader, which is known as an autoimmune response. When the immune system attacks tissue within the brain, it causes damage to the local neurons and leads to destruction of brain tissue.

 photo by: kristen thomas

photo by: kristen thomas

The immune response in the brain is controlled by cells called microglia. These cells act as the guard dogs of the central nervous system, both defending against infections and scavenging damaged cells and waste found around the brain. Much like certain dogs, they can have extremely strong reactions to even small disturbances. This sensitivity, while quite advantageous for quickly responding to threats, can also have major consequences if they become so sensitive that they start attacking human tissues. Once the microglia are activated, they release molecules that trigger inflammation in surrounding tissue. Inflammation is a process that normally helps to eliminate the initial cause of an injury and help with tissue repair, but persistent inflammation will result in significant cellular damage. Moreover, this response actually makes it more difficult for the body to clear beta amyloid plaques, causing a negative feedback loop that results in even more plaque deposition in the brain.

Adding more evidence to this theory, a new study published in the Journal of Alzheimer’s Disease on February 2015 by the Bieberich lab at Georgia Regents University demonstrated that an autoimmune response might be responsible for the progression of the disease. Researchers have discovered that a molecule called ceramide, mainly found in membranes surrounding cells throughout the body, can be targeted by the immune system. This immune response causes an increase in antibodies that destroy ceramide in the brain. The researchers found that when amyloid beta plaques start to build up in the brain, certain cells begin producing more ceramide. The ceramide is then targeted by the immune system, causing inflammation and increasing the amount of amyloid beta in the brain. These new studies suggest that our own immune response, then, may be what is ultimately responsible for the advancement of the disease.

While we may still not know the root cause behind the mystery of Alzheimer’s disease, these new findings have revealed another important clue, which is that autoimmune responses may play a significant role in the progression of the disease. One of the exciting aspects of this research is that it opens up a whole new set of opportunities to treat Alzheimer’s using therapeutics that target the microglia or reduce inflammation in the brain, which may be able to slow down the progression of the disease. More effective treatments are sure to significantly address the mounting healthcare costs associated with the growing population afflicted with this disease. More importantly, these new treatments have the potential to provide life-altering relief to those currently suffering from Alzheimer’s.

Edited by: Marika Wieliczko

Welcome to Inscripto: Letter from the Editor

Anzar Abbas

Originally published April 1, 2015

 photo by: kristen thomas and jadiel wasson

photo by: kristen thomas and jadiel wasson

Hello everyone, and welcome to the Spring 2015 Issue of Inscripto. My name’s Anzar Abbas and I’m a PhD student in the Neuroscience Program at Emory. I was approached last fall by Yun Wei, a fellow graduate student, about restarting an old student organization called the Science Writers Association of Emory. It was an effort made by past graduate students to write about science in a way that would be interesting to the public.

Unfortunately, as those students graduated, SWAE dissolved as well. Yun was able to drum up interest for the group from just enough people, and we embarked upon a mission to recover and relaunch SWAE and its publication, Inscripto. It’s been a challenge, but I’m glad to say we’re finally getting on our feet.The Spring Issue of Inscripto has twice as many contributors than the fall, and we’re proud to launch all of those insightful articles on our brand new website so they’re even easier to read and share amongst your friends.

SWAE’s aim is to provide an opportunity for students at Emory – particularly those working in the STEM fields – to participate in the popular communication of science. They are welcome to write about current issues in their field, topics of public interest, and even their own research. It’s an exercise that hopes to foster a generation of scientists that are better connected to the public, and play a more central role in the delivery of scientific knowledge to the masses.

We hope to do this partly through Inscripto, which aims to provide a comfortable introduction for a scientist to the world of popular science communication. I thank everyone that chose to contribute to the Spring 2015 Issue of Inscripto, especially those who were embarking upon popular science writing for the first time. Most of all, I invite all others to ponder the possibility of contributing as well. Sure, it’s a bit of effort and time. But it easily redeems itself in lessons and an appreciation of the difficulty of explaining complex ideas simply. There is beauty in communicating science in layman’s terms.

Lastly, this publication could not have been possible without every bit of effort from our entire team. I wanted to thank Brindar Sandhu, our Managing Editor, for her leadership and work in producing this Issue, along with our wonderful Associate Editors, Bethany Wilson and Marika Wieliczko. Responsible for the impeccable design behind the text on every page are our talented Design Editors, Kristen Thomas and Jadiel Wasson. If you aren’t reading this in print, you must be reading it online, and for that I would like to thank Sara List for countless hours towards the development of SWAE and Inscripto’s website.

Hope you enjoy the issue!
Until next time
Anzar Abbas
Editor-in-Chief

Alzheimer’s Disease: A Scary Monster for Adults

Claire Galloway

Originally published March 6, 2015

 photo by: kristen thomas

photo by: kristen thomas

As a child, you may have feared dying at the hands of ghosts, zombies, and witches. As an adult, you have probably outgrown your irrational fear of monsters creeping into your room to quickly kill you. Instead, now you may harbor an all-too-rational fear of Alzheimer’s disease creeping into your brain to kill you in a torturous and demeaning manner, and slowly stealing all your memories in the process. If so, you are not alone. Over 1 in 5 adults were more fearful of developing Alzheimer’s disease than almost any other disease – second only to cancer.

Unfortunately, simply learning the facts about Alzheimer’s disease prevalence and treatment options is enough to strike fear in the bravest of hearts. Currently, 5 million Americans 65 and older have Alzheimer’s disease. If the disease incidence is left unchecked, this number is expected to exceed 7 million over the next 10 years. Prepare yourself for the scarier news: no one has found a silver bullet to stop the disease. Although research into Alzheimer’s disease has been ongoing for over a century, it is still unknown what causes the vast majority of Alzheimer’s disease cases. Similarly, the three drugs that are FDA-approved for the treatment of Alzheimer’s disease prevent symptoms of the disease, such as cognitive decline… temporarily… in roughly half the patients. Many other drugs that were developed to target the underlying disease mechanisms have shown promise when tested in animal models, but none have proven to be viable treatment options when tested in humans.

If you haven't already thrown down this magazine and run away in terror, take heart. It is not as if you are completely defenseless against the Alzheimer's disease monster. In actuality, there are lifestyle choices you can make now to reduce your risk of Alzheimer's disease. As you may have guessed, many choices that are linked to overall health are also correlated with a reduced risk of Alzheimer's disease. For example, eating a diet low in saturated fat and high in fresh produce, as well as exercising - even if it's just a slow walk – may reduce your risk of developing Alzheimer’s disease.

In addition, new and creative research directions are flooding the shadowy field of Alzheimer's disease research with light. Using in vivo electrophysiology to record from animal models of Alzheimer’s disease has potential to help researchers understand how Alzheimer’s disease alters communication between brain regions as animals are awake and even performing memory tasks. In vivo electrophysiology studies the electrical properties of cells within living animals, and can be used to measure the activity of cells within a specific brain region at a millisecond time scale. In the context of Alzheimer’s disease, this technique could offer insight into if and how the protein abnormalities that characterize Alzheimer’s disease change the nature and quality of communication between regions of the brain before cells actually begin to die.

For example, studies in Alzheimer’s disease patients show that the hippocampus, a brain region that is important for memory and disproportionately targeted by Alzheimer’s disease pathology, changes dynamically as Alzheimer’s disease progresses. In very early stages of Alzheimer’s disease, hippocampal neurons are hyperactive. Later in Alzheimer’s disease, hippocampal neurons become underactive. One important function of hippocampal cells is that, by selectively increasing their firing rate in distinct locations of a given environment, collectively these cells create a mental map of the environment. The mental map of rodents who are aged, or given drugs that impair memory, is degraded. In vivo electrophysiology techniques will allow researchers to record from the hippocampus of rodent models of Alzheimer’s disease, and tell us whether brain changes during early stages of Alzheimer’s disease interfere with the ability of hippocampal cells to provide an accurate and reliable mental map of spatial location. Not only could this research help us gain a better understanding of how Alzheimer’s disease attacks our brains, it could be used as a sensitive measure to evaluate how new therapeutics affect brain function before being tested in humans.

So, if you or your loved ones can't sleep at night over the fear of Alzheimer's disease, rest a little easier knowing there are practical steps you can take to reduce your risk of disease, and that Alzheimer’s disease researchers are working around the clock to beat one of your scariest adult monsters.

White Noise Syndrome: An emergent disease battering North American Bat populations

Brilee Coleman

Originally published March 5, 2015

 Photo by: Brilee Coleman

Photo by: Brilee Coleman

If you think bats flying out of haunted houses are scary, imagine finding thousands of bat bodies lying around in the woods one morning. This is exactly what happened when White Nose Syndrome, or WNS, was discovered in 2006, and Myotis lucifugus (little brown bats) were discovered strewn outside of caves in New Albany, New York. WNS is a fatal disease named for a fungal infection found on the noses of hibernating bats. The disease kills bats by causing them to rouse from hibernation prematurely, after which bats wander out into the daylight in the middle of winter, where they die from lack of food and low temperatures. Typically, hibernating bats venture deep into caves where they seek shelter for the winter, called hibernacula. Bats affected by WNS, however, can be found hibernating at the mouths of caves, where temperatures are less stable. These changes in bat behavior have resulted in a loss of 5.7 million to 6.7 million bats of at least 11 different species since the discovery of WNS in 2006. It is believed that WNS was brought to North America from Europe, where the disease is present, but bats are unaffected. Because bats do not travel between continents, it is likely that WNS was transported on the shoes of cavers traveling from Europe to the United States. Since its arrival in North America, WNS has been documented in 25 states and several Canadian provinces.

So how does having a “white nose” result in strange hibernation behavior and death in bats? Hibernating bats have decreased metabolic activity, which allows them to survive the winter by slowly burning off fat stores for energy. Unfortunately for the bats, decreased energy expenditure also leads to suppressed immune function, leaving them vulnerable to infections. Research has shown that WNS is caused by a previously unidentified fungus, Pseudogymnoascus destructans. P. destructans is a psychrophilic (cold-loving) fungus that only functions at temperatures below 20°C, making bat hibernacula perfect environments for fungus growth. Infection of bat tissue with P. destructans leads to more frequent arousals during hibernation, which can result in increased energy expenditure and premature emergence from hibernacula. In the event that bats do survive through the winter, they emerge from hibernation in a weakened state. Because of WNS, even the little brown bat, the most common bat species in the United States, is in danger of extinction.

Why is preventing WNS important?

Bats are critical members of North American ecosystems, and humans benefit greatly from their presence. They are excellent pest control agents, consuming over 1,000 mosquito-sized insects per bat every hour. Many of these bugs are forest or agricultural pests that we would otherwise spend an estimated $3 billion per year paying to control. While bees may get most of the credit for pollination, bats are often-unsung heroes of pollination themselves. If you enjoy having tequila made from agave plants with a side of guacamole made from avocados, thank the bats responsible for pollinating both. Among other plants, bats are also known to pollinate bananas, mangoes, cocoa, and guava. Downstream of initial loss of pest control and pollination of avocado crops, the extinction of North American bat species would likely have major unknown consequences on both economic and ecological health in affected areas.

In addition to having an ecological impact, bats have also served as inspiration for human innovation. Bat Simultaneous Localization and Mapping (BatSLAM) is a radar system modeled on bat echolocation. BatSLAM helps solve the problem of robots navigating and localizing themselves in complex environments, allowing for the development of more autonomous robots.  In addition, biomimetic skins modeled on bat wing properties have allowed for unprecedented flying capabilities in small aerial vehicles, such as controlling various wing shapes and flight modes mid-flight.  Without access to bats for research purposes, these efforts would likely come to a halt.

What is being done about WNS?

There is currently no cure for WNS, although it remains an active area of research. In the absence of a cure, conservation of bat habitats and quarantine of affected caves are critical steps in the effort to prevent the spread of WNS. Current approaches include closing off caves known to be contaminated with WNS and using biosecurity measures to prevent cavers from introducing WNS to caves that are known to be clean. Some things that everyone can do to help prevent the spread of WNS are reporting strange bat behavior, such as flying during the day, to the Georgia Department of Natural Resources, staying out of bat hibernation sites, limiting disturbances to natural bat habitats around your home by reducing outdoor lighting and minimizing tree clearance, and educating others on the many values of bats.  For those interested in actively participating in bat conservation, the Georgia Department of Natural Resources provides information on how to build bat roosting boxes and other volunteer opportunities at their website: http://www.georgiawildlife.com/Conservation/Bats. For more information about WNS, visit: https://www.whitenosesyndrome.org/.

What missing link? Filling the 'holes' in the theory of evolution

Kristen Blanchard

Originally published March 4, 2015

 Photo by: Kristen Thomas

Photo by: Kristen Thomas

When Georgia Congressman Paul Broun was asked about his views on evolution, he claimed it was an idea “straight from the pit of hell.” However, despite being framed as a conflict between religion and science, the basic tenets of evolution do not preclude faith or religion. Unfortunately, the topic of evolution still evokes passionate debate from both supporters and detractors, such as the one that occurred between Ken Ham and Bill Nye earlier this year. Sadly, in many of these debates, those who disagree with so-called Darwinian evolution disseminate information that simply isn’t true. Such misinformation hinders the public’s conception of evolution and obscures the true questions that still remain in our understanding of how organisms change over time. What follows are some of the common misconceptions held by opponents of evolution and the reasons these talking points are false.

The fallacy: It’s possible to believe in both evolution and Intelligent Design.

Some proponents of Intelligent Design, Creationism, or other “alternatives” to the theory of evolution will argue that their views can coexist with those of evolution. They might argue, for instance, that there is no disagreement. They agree that organisms change over time, hence, they accept that evolution occurs. They just believe it occurs as part of a directed and pre-planned course.

The facts: The theory of evolution is directly antithetical to pre-planned, “directed” series of changes.

Evolution occurs through a series of random changes. In a large enough population, mutations will occur, leading to genetic diversity. The genes that are best at propagating (i.e., the “fittest”) will propagate the most and become the largest portion of the population. On an individual level, the organisms that are thus best at reproducing will reproduce the fastest, and overtake the population. To argue that these genetic mutations are not random, but rather preordained, runs directly counter to the definition of evolution. This distinction may seem like an issue of semantics – if both sides agree that organisms change over time through genetic mutations, why does it matter whether these changes are random or planned? The answer is because the latter runs contrary to what scientists see in the lab. As scientists monitor organismal changes over time, mutations are random. Populations experience both beneficial and deleterious mutations, not merely preordained changes according to a design. This observation forms the foundation how we understand genes, proteins, and whole organisms to change over time. Applications of evolutionary science, such as tracking infectious disease transmission, would be impossible without this framework for understanding how changes occur. Thus, to argue that evolution and Intelligent Design are synergistic theories is simply disingenuous.

The fallacy: Entropy disproves evolution – the natural tendency is for things to become more disordered, not more complex.

The second law of thermodynamics states that in a closed system, entropy can never decrease. Technical jargon aside, this immutable postulate means that absent outside influence, things cannot become spontaneously more ordered. An unordered set of molecules cannot suddenly become ordered without external force. For opponents of evolution, this argument means that the development of complex biological structures (i.e., living organisms) requires a designer in order to be consistent with this law of thermodynamics.

The facts: The energy provided by the sun powers the creation of ordered molecules.

The important caveat in the second law of thermodynamics is that it holds true for a closed system. With external input, entropy (or disorderedness) can decrease. This input can take many forms, without necessitating the existence of a designer. For example, we know that plants can utilize energy from the sun to form sugars from smaller molecules. Entropy decreases due to the addition of energy to the plant. Our natural environment is not a closed system. Energy is constantly added to the system and no external designing force is needed to explain the decrease in entropy as life forms evolved.

The fallacy: Scientists have never observed speciation, or seen the evolution of new or separate species.

Some opponents of evolution also make the distinction between “microevolution” and “macroevolution.” They might concede, for instance, that bacterial populations can develop antibiotic resistance over time, but argue that bacteria can’t evolve into separate species. Implicit in this claim is that such evolution, the development of offspring into separate or new species, has never been directly observed.

The facts: Large-scale organismal changes have been observed both in the lab and in nature.

The Cohan laboratory at Wesleyan University studied adaption over time in communities of Bacillus subtilis, a type of bacteria. In this experiment, not only did they observe B. subtilis descendants develop into unique ecological subtypes (“macroevolution”), they observed that these drastic changes occurred on a similar frequency as changes within an ecological subtype (“microevolution.”) In fact, most scientists do not make a distinction between microevolution and macroevolution. As the work of the Cohan laboratory shows, both small-scale changes and large-scale changes happen concurrently as organisms reproduce; microevolution and macroevolution are occurring through the same process.

Despite our certainty that evolution can and does occur, there are plenty of exciting questions that remain. Research is constantly underway to refine our understanding of evolution. In fact, labs here at Emory are currently investigating diverse topics ranging from evolution of antibiotic resistance to host parasite interactions. The question of how organisms evolve is still a rich and exciting mystery – but that they evolved, and continue to do so both in nature and in the laboratory, is simply not up for debate.

You Can Handle The Truth: What You Can Learn From Your Own DNA

Zachary Ende

Originally published March 2, 2015

 photo by: jadiel wasson

photo by: jadiel wasson

Samuel L. Jackson is known for a plethora of apoplectic soliloquies, but you’ve probably never heard him say, "Wow, get out of here! I have to Google Gabon immediately, and see what’s there!" If you thought this was hyperbole-laden acting, you would be surprised to learn that he was reacting genuinely. All it took was the science of DNA. On the television show "Finding Your Roots," Samuel L. Jackson learned his DNA matched that of the Benga tribe of modern day Gabon, sparking his interest in the Central African nation.

The connection was made possible by Africanancestry.com, one of nearly a dozen personal genome sequencing companies that have sprouted up to decipher your DNA. Why now? DNA sequencing costs have plummeted precipitously as technology has rapidly evolved. Decoding an entire human genome went from over $100,000,000, in the year 2000, to $1,000,000 in 2007, to under $10,000 today. Most personal genome sequencing companies probe short informative regions of your DNA. These private companies can tell you amazing things about yourself. What kinds of things are hidden in our DNA?

All of humanity originated in East Africa roughly 150,000 years ago subsequently spreading throughout the world. For about $200, the National Genographic Project traces your ancestors' migration to the present day solely from skin cells on the inside of your mouth. They decode small portions of your skin cell derived DNA known to differ between people (single nucleotide polymorphisms or SNPs, pronounced "snips").

At most times during human evolution, more than one hominin species lived concurrently. Our habitually besmearched cousins, the Neanderthals, lived alongside modern humans up to about 30,000 years ago. In a landmark study published in 2010, Green et al. examined Neanderthal DNA in modern humans and showed that "non-African haplotypes match Neanderthal at an unexpected rate." Since then, other publications have suggested mixing probably occurred in the Middle East about 50,000 to 60,000 years ago. For non-Africans the average match to Neanderthal DNA is ~2%. You may find out you are part Neanderthal, literally.

I am admittedly a bit of a Neanderthal. How do I know? I tried 23andMe for $100. I also learned much more relevant information about my genetic predispositions. Some of the propensities they test for may surprise you: drug side effects (i.e. statins for cholesterol), diseases (i.e. various cancers, asthma and dementias) and, physical and metabolic traits (i.e. height, food preference, and aging).

These tests also surprised the Federal Drug Administration (FDA) of the United States government. The FDA told 23andMe to "immediately discontinue marketing" in an official warning letter on November 22, 2013, until approval is granted for the health risk assessments (though they still give you the raw data). Why would the government block us from potentially valuable health information found in our own DNA?  

The warning letter cited concerns "about the public health consequences of inaccurate results." The FDA categorized the DNA service as a medical device and thus expressed concern about false negatives, false positives, and misinterpretations by consumers that could lead to bad healthcare decisions.

Not everyone supports the FDA's decision. Robert Green is one formidable dissenter if there ever was one. He is an M.D., M.P.H. in the Division of Genetics at Harvard Medical School and is also part of "The Impact of Personal Genomics Study." In a comment in the journal Nature, Green and Nita Farahany, a law professor at the Duke Institute for Genome Sciences and Policy, said that "a US drug-agency clampdown is unwarranted without evidence of harm," and, " we urge the FDA to let consumer genomics testing proceed." Most people (~60%) do nothing when learning of their genetic risk factors, while over a quarter of people change exercising and eating habits for the better. Other articles in the Journal of the American Medical Association and the New England Journal of Medicine support the FDA's decision, though Green and Farahany's arguments are the most convincing since they have actually studied the issues in play.

Putting aside the argument about the paternalistic stance of the FDA, maybe this information is too heavy for many of us to consider knowing on an emotional level. After all, besides the disease risks, we could find unknown half siblings (search "With genetic testing, I gave my parents the gift of divorce" for an interesting story about an anonymous 23andMe customer who reported just that). On the other hand, knowledge is power, and perhaps you will discover important facts about your genetic risk factors for you and your children.

Of utmost concern is privacy and data security. The Genetic Information Nondiscrimination Act of 2008 protects those in the United States from discrimination based on genetic information in the realm of insurance and employment. That information alone is not enough to allay most people's fears. Most would-be consumers I have spoken with said privacy is paramount in their minds and the top reason for not participating in personal genome sequencing.

23andMe may as well be considered a side project of Google given that 23andMe CEO Anne Wojcicki is the wife of Google Co-Founder Sergey Brin (it is not just gossip, it is also a $3.9 million investment in 2007). Google's connection is unsettling on the one hand given the fear that our own DNA could end up being "Googled" or worse yet added to the ungodly amounts of data Google has on us.  On the other hand, Google is a technological mammoth that one would imagine has resources and know-how to protect private information—if anyone can.

I shared my 23andMe results with any of my family members that would listen—both ancestry and health-related analyses. My own experience was a journey of self-discovery and personal empowerment; friends who have tried the service have echoed that sentiment on the whole. Nevertheless, improved sequencing methods leading to lower costs and a better understanding of the results will enable a more complete DNA decoding experience than the "snips" currently offer. That is why, for those considering paying for DNA sequencing services, like those considering purchasing the newest computer or smart phone, you will likely be rewarded for your hesitation and indecision. As soon as you buy the new version, the newer improved version comes out a day later. But hey, like DNA, to each his own.

Ebola: From Science to Treatment

Erica Bizzell

Originally published October 31, 2014

ebola.jpg

Ebola… this is the word on everyone’s lips over the past few months, and rightly so. Since its discovery in the late ‘70s, there have been five species of the Ebola virus in circulation, which up until recently caused a little over 2,300 total cases of human infections.  With close to 9,000 cases of Ebola in West Africa just since March of this year, and a mortality rate of at least 50%, this is by far the most widespread Ebola outbreak in recorded history. The Zaire strain of Ebola (EBOV) has been the culprit behind the majority of major human outbreaks throughout the past four decades, and is the strain currently in circulation.  However, two major questions remain: (1) What makes this Ebola outbreak so different than all the previous ones, and (2) What steps are currently and should be taken to combat this deadly virus?

So what is it that makes this particular outbreak so unique?  Your first response may be to “blame the virus”.  Some viruses, such as HIV, are known to have rapid mutation rates that alter the course of disease over time, which leads many to wonder if this is what underlies this particular outbreak.  However, mutations do not appear to be responsible for the current spread of Ebola. The first Ebola case study, reported in the New England Journal of Medicine by Dr. Sylvain Baize et al., revealed that the virus is 97% identical to EBOV strains from the DRC and Gabon.  With viral mutations not being the driving force behind the outbreak, we must turn our attention to something besides the virus.  The unprecedented magnitude of this outbreak is mostly due to a host of social factors, including inadequate basic hygienic tools during treatment (such as private bathrooms), distrust of government due to continued civil unrest, as well as porous borders allowing for unchecked travel between affected areas.  All of this has contributed to the formation of a “perfect storm” scenario for the spread of this virus.  

Considering that the current Ebola species in circulation has been around since the discovery of the virus, one can’t help but wonder what advances have been made to contribute to treatment or prevention.  Many people have now heard of the experimental drug ZMapp, which was used during treatment of the first two Ebola patients in the United States.   Through research conducted in the lab of Dr. Gary Kobinger, this drug, consisting of a cocktail of antibodies against Ebola, was shown to be effective in primates when administered early (up to five days post-infection) during viral infection.  While no studies have been published to determine the effectiveness of the drug further into disease progression, this is a significant step in the right direction for treatment of Ebola.  

Measures are currently being taken to address prevention of Ebola.  At the WHO Consultation on Ebola Vaccines on September 29-30 of this year, it was decided that the testing and production of the two most promising Ebola vaccines be expedited.   Both vaccines are currently ready for phase I trials, meaning that they have already shown adequate safety and efficacy in at least two different animal models.  One of these vaccines, now being produced by GSK in collaboration with the US National Institute of Allergy and Infectious Diseases, has had very promising results in initial studies with primates.  In a publication from the NIH Vaccine Research Center lab of Dr. Nancy J. Sullivan this September, the ChAd3(Z) vaccine conferred 100% protection to animals challenged with a lethal dose of Ebola. These along with various other studies provide some hope for the future of Ebola treatment and prevention.  

Here at Emory, much is already being done at the clinical level to fight Ebola.  At the Emory University Public Health Sciences Grand Rounds on September 19th, the Emory community was given a peek into the treatment regimen of the first two United States citizens infected with Ebola treated here at Emory.  Dr. Marshall Lyons explained the many considerations that had to be addressed in order to treat these patients here in the U.S.  One can only imagine the logistics behind coordinating a team of over 120 people for the care of these two patients.  While the experimental drug ZMapp was included in the patients’ treatment regimen, there was a host of supportive therapy that was critical for the survival of these two patients including but certainly not limited to administration and monitoring of fluids, electrolytes, ventilation, life support, and blood transfusions. The use of adequate sanitation, full isolation of the patients during treatment, and the work of professionals in proper personal protective equipment made it possible for both patients to walk out of the hospital completely healthy. Through the panel discussion at this event, we learned that collaborative efforts are now being made by the CDC along with other health groups around the world to bring some of the more basic medical standards, which we have in the US, to the West African countries most affected by the current epidemic.  It is clear, however, that in order for there to truly be a long-term resolution to the issue of Ebola in this region, more efforts will need to be made both to restore public trust in government and to build an adequate infrastructure for health care in the countries affected.

Possessed: Demons of the Mind

Kristen Thomas

Originally published October 31, 2014

 photo by: kristen thomas

photo by: kristen thomas

One day your teenage son becomes convinced that someone is in his head. This person provides a running commentary on your son’s life and every move he makes. Your son can hear this voice as clearly as yours when you stand before him. Your son socially withdraws from you, his friends, and everyone else, and this voice becomes his only companion. When your son does speak to you, it seems disjointed and confused. Then one day reveals that the voice in his head belongs to a demon, and this demon has taken control.

Although this may sound like the first 30 min of the latest exorcism movie, psychiatrists would recognize these behaviors as symptoms of schizophrenia, a neurodevelopmental disease that affects approximately 1% of the world’s population. Hallucinations (e.g. hearing voices) and delusions (e.g. believing someone possesses control over a person’s actions) are perhaps most commonly associated with schizophrenia, but the symptoms of schizophrenia are diverse and complex. Other symptoms may be cognitive (e.g. disorganized thinking and speech) or negative (e.g. social withdrawal and depression). No two patients have exactly the same symptom profiles. Most patients first develop symptoms in their late teens or early 20s and battle this disease for their entire lives.

The Dark History of Schizophrenia and Mental Illness

According to a 2008 survey, 85% of people understand that schizophrenia is an illness with a physical basis, yet throughout history schizophrenia and other forms of mental illness were thought to be the result of demonic possession or witchcraft. During the Middle Ages and Renaissance, the Catholic Church promoted the view that people who suffered from mental illness should be treated through religious means: confession in the case of witchcraft or exorcism to remove the demon spirit. Perhaps consequently, those who suffered from mental illness were treated with fear and disgust.

The first asylums opened in the 14th century and used brutal means to control its mental patients. Patients were often chained to the walls or fastened to their beds. In extreme cases flaming pitch was applied to the patient’s head. Mental patients only began to experience more humane treatment in the 18th and 19th centuries. However, even these “humane” treatments included bloodletting, a prolonged withdrawal of blood that also sedated unruly patients by weakening them. Throughout history the horrors suffered by mental patients have been far more worthy of Hollywood’s horror film genre than the behaviors of the patients themselves.

Although schizophrenia patients receive more humane treatment today, the belief that their condition may be the result of demonic possession rather than a brain disorder still resurfaces. Any Google search for “demons and schizophrenia” will yield a variety of spiritual and occult websites claiming to be able to differentiate demonic possession from schizophrenia. In June of this year, the Journal of Religion and Health published an article by the Turkish researcher M Kemal Irmak. According to the author, demons reside in a parallel world, unseen by most humans, but they may also possess and control humans. He also claims that many modern cases of demonic possession have been misdiagnosed as schizophrenia and urges medical doctors to enlist the services of faith healers in such cases.

A Scientific Interpretation: Debunking the Demon Myth

Science is equipped to deal with exploration of physical phenomena within our own world––not that of demons. However, decades of research have shown that the symptoms of schizophrenia are due to physical changes within the brain, and they may be treated using medical rather than religious means.

The first antipsychotic medications were introduced during the 1950s. Early and modern antipsychotics alleviate positive symptoms as well as some of the cognitive symptoms of schizophrenia by blocking the activity of dopamine, a signaling molecule within the brain. No approved antipsychotics treat the negative symptoms, which are often debilitating. Fortunately, many schizophrenia patients are still able to lead productive, independent lives under a lifelong treatment regime.

The last few decades have also greatly expanded our understanding of the physical basis of this disease. Schizophrenia is highly heritable: if one identical twin is diagnosed with schizophrenia then the other twin has about a 50% chance of also developing the disease. The genetics of schizophrenia are highly complex, and thousands of different genes have been linked to schizophrenia, many of which have also been linked to autism, Tourette’s syndrome, or other cognitive disorders. Environmental factors, including early life stress and drug abuse, also appear to interact with genetic factors to further influence disease development.

Perpetuating the Stigma of Schizophrenia

Despite the advances made in our understanding and treatment of schizophrenia, the average patient experiences a nine year delay between their first symptoms and first diagnosis and treatment. Part of the problem is misdiagnosis: other mental diseases, including major depression, can have similar symptoms. Furthermore, many physicians are reluctant to diagnose a patient with schizophrenia due to the stigma that many patients experience following diagnosis.

Schizophrenia is one of the most highly stigmatized diseases in our society. Many patients are reluctant to tell others about their diagnosis because many people are afraid to work with, date, or admit that they are related to someone with schizophrenia. This stigma not only delays diagnosis but also means that at any given time more schizophrenia patients are homeless or imprisoned than in a mental hospital. Stigma also affects the allocation of research funds: schizophrenia receives less funding per person affected than other mental disorders, e.g. Alzheimer’s disease or depression, yet schizophrenia is one of the most costly diseases to society.

 photo by: kristen thomas

photo by: kristen thomas

If most people recognize that schizophrenia is a physical illness, then why does this stigma still exist? After millennia of association with supernatural and often evil forces, our society has been slow to accept the mentally ill without fear or reservation. The news media reinforces this stigma by reporting on crimes committed by those suffering from untreated mental illness, though patients are far more likely to harm themselves than others. As you view The Exorcist and similar horror flicks this Halloween, ask yourself whether these films also perpetuate the stigma. The myth of demonic possession and the history of schizophrenia have been closely entwined for centuries, and science must continue its work to disentangle them within our society.

A Murder of Crows

Jadiel Wasson

Originally published October 31, 2014

 Photo by: Kristen Thomas and Jadiel Wasson

Photo by: Kristen Thomas and Jadiel Wasson

In the spirit of Halloween, this is a tale of fiction shrouded in fact: A slight exaggeration of the natural ability of the magnificent family of birds known collectively as the Corvidae family.

Imagine this: You are walking alone in the park on a foggy morning with only the pale morning sun to guide you. *Caww*  What was that? *Swoosh.*  Something lands on your bag. You swing it in an attempt to thwart the menacing perpetrator. You move to investigate the damage and realize it is only a crow with a piece of your bagel in its mouth. Your sigh of relief is stifled with the thickening of the air with sounds like the fluttering of thousands of bird wings. A murder of crows has been incited. You immediately make your exit and run to work, afraid of what you have started.

You may have escaped the peril. But what you do not know is that the crows will remember your face.

Crows have an unparalleled ability to recognize and remember faces. To test this ability, a Seattle group of scientists captured and tagged crows while wearing a variety of different masks. Two years later, the crows were able to recognize the masks and remember the misdeeds of the researchers leading to harassment and admonishment of the researchers. This ability to create a negative association with certain people and their behaviors was traced to a particular brain region by another group of researchers. They also observe differential brain regions becoming activated as crows processed human faces. These studies reveal how crows can integrate memory and perception to adapt accordingly to their surroundings.

That night, you are walking home from work, forgetful of your early morning transgression. *Squawk! Squawk!* It begins with one. Then like an avalanche, all of the crows join in a chorus of horror. They dive bomb as only angry birds can. *Crack* You’ve just been hit with a massive object… was that a weaponized nut? It is almost as if the crow who threw it knew what angle and height to drop it from to incur the most damage.

  PHOTO BY: KRISTEN THOMAS AND JADIEL WASSON

PHOTO BY: KRISTEN THOMAS AND JADIEL WASSON

In fact, it has been well documented that crows can calculate the height and velocity it takes to crack a nut with the least possible damage to the treasure inside. They are even able to deduce environmental clues as once the nut has been dropped on the street, they have the cognizance to wait for traffic to stop in order to jump into the street and collect the spoils. This cold calculation also extends to food storage. Crows, like few other animals, store food away for future use but take it two steps further. In a series of studies analyzing the ability of crows to adjust storage tactics, crows demonstrated not only an ability to deceptively hide food from thieving on-lookers with a “slight of hand” stratagem, they also altered food storage times to account for perishability of food.  These behaviors demonstrate predictive and causal thinking, signs of higher cognition.

Once the crows start using heavy artillery, you realized how much danger you really are in. You sprint home and lock the doors. From your balcony window, you can see that they have tracked you down. They appear to be fashioning small tools from the barbed succulents outside of your apartment, all in the same manner with the same directional tendency.

The ‘handedness’ of crows has been documented to be not only at the individual level but also appears to exist at the social/cultural level in crow species. It hints to brain laterality where there is a division of labor between the two hemispheres, leading to the ability to coordinate actions. It is also important to note that crows do in fact have “cultural” behaviors as it has been documented that crows talk to each in regional dialects.  

Stepped tool making, which has mostly been observed in primates, has been well documented in crows, highlighting their high cognitive function. Studies show that not only can crows decipher which tools would be the most appropriate to complete a specific task (i.e. . choosing proper diameter and length of a stick to retrieve food), they also have the ability to generate these tools. Crows have been documented to independently generate tools in order to complete specific artificial tasks that would not be encountered in the wild. Imagination is considered one of the hallmarks of high cognitive function.

What are they going to do with these barbed tools? The thought is maddening as they fly up towards your balcony window and realize you pet tarantula has been left out for air. As they spear your beloved pet before your eyes, you begin to realize this probably will not end well. They begin to pick the lock to gain access to your apartment. Why are they so smart?

In fact, crows do in fact use small spear-like tools in the wild to forage for insects along the forest floor. Small hook shaped tools are used to gather larvae from trees.

Based on brain to body size ratio, crows have a brain capacity on par with non-human primates. Structurally, their brains are very different while functionally there are certain areas of their brains that are analogous to primates. The region of the brain that is responsible for cognition is enlarged in the Corvidae family compared to other birds. They share the four basic hallmarks of cognition with apes: imagination, flexible knowledge and learning ability, causal learning and prospection. Granted, they cannot pick a lock, but they do have the ability to generalize knowledge and apply what they have previously learned to a novel situation. This allows them to be highly adaptive animals, which is a large reason for their success in urban areas.

*Click* The lock has been picked. The last thing you hear: the fluttering of wings. Who knew how intelligent a bird could be?

What makes crows an interesting paradigm in evolutionary history is that their intelligence is an extreme example of parallel evolution.  Crows have diverged on the evolutionary tree over 100 million years, and as a result have very differently structured brains compared to mammals. Mammals were thought to be the only animals that can possess high cognitive function, thus leading to the idea that their brain structure conferred this ability. Despite the large differences in brain structure, crows are becoming recognized as being just as intelligent as primates. Ultimately, crows represent a great model for how intelligence and cognition can evolve independently throughout evolution.