A Study in Vivo (A Diagnosis of Will Graham)

Even for a fictional character whose daily work is chasing after psychopaths and serial killers, Will Graham has some pretty poor health habits. He drinks – and I mean drinks whiskey and tea and coffee (anything but water) – and pops aspirins like he’s eating candy. He is sleep-deprived and hallucinates (later we discover that he has encephalitis). Halfway through season two of Hannibal, I found myself wondering whether these symptoms were realistic, or exaggerated for the television screen. Thus began the research.

Now, for the entirety of my life, up until one week ago, I did not know what a kidney was.

I knew what a kidney was – I’d heard of kidney transplants and organ donors and the organ black market. But truly, I didn’t know what a kidney did.

So for those of you who don’t know what a kidney does – this is what a kidney does.

The digestive system is where you eat food and secrete unabsorbed matter in the form of feces. An entirely unrelated system is the excretory system, where you filter bad stuff out of your blood and dispose of it (mostly nitrogenous waste) in the form of urine. I did not know that two weeks ago. Truly.

A kidney, along with your skin, intestine, liver, and lungs, helps your body with osmoregulation – the active regulation of bodily fluids to maintain homeostasis. Your kidney has several key functions: filtration of unnecessary solutes and some water out of your circulatory blood, selective reabsorption of needed water and solutes back into your blood, secretion of unwanted solutes into urine, and excretion of concentrated urine (which now consists of nitrogenous waste, unnecessary solutes, and toxins. See image one).

When there are too many solutes in your blood, or high blood osmolarity, the body releases a hormone called antidiuretic hormone, or ADH. ADH is responsible for increasing the retention of water in your kidneys. In other words, when there’s ADH floating around, your kidneys recognize that you need to decrease the osmolarity of your blood; thus, they reabsorb water from what would eventually become your urine.

ADH amplifies water reabsorption, which in turn, reduces urine volume, and overall, helps prevent the increase in blood osmolarity.

High blood osmolarity leads to a high blood pressure. Which is bad. Because, heart attacks. And extra stress on your heart.

The opposite occurs when your body detects low blood osmolarity levels. Little ADH is produced, leaving your body to decrease the permeability of the tubes on your kidney, allowing less water to return to your body (see image two). Little ADH increases the volume of your urine.

However, alcohol and caffeine can disturb water balance by inhibiting the release of ADH, which causes excessive urinary water loss and dehydration – which may cause some symptoms of a hangover.

With that in mind, let’s think about our friend Will Graham for a minute, from NBC’s Hannibal. Mr. Graham is rather fond of coffee. And tea. And whiskey. All of which are sources of alcohol and caffeine. Never once, in all of the shows’ three seasons, can I remember Will Graham drinking water. Maybe I forgot.

Either way, dehydration is bad.

Secondly, aspirin. The purpose of aspirin is to reduce the pains of headaches, fever and inflammation.

In a localized inflammatory response, damage to human tissue by pathogens or physical injury leads to the release of histamine. Histamine is a chemical that triggers dilation and increases the permeability of capillaries and veins. Other activated compounds like prostaglandins promote blood flow to the affected area, subsequently causing inflammation as expanding capillaries leak into neighboring tissues. Blood clotting serves as a blockade, preventing the spread of microbes. However uncomfortable, this inflammation is an innate process that assists with defense against bacteria.

Back to aspirin. Aspirin prevents platelet aggregation and subsequently “thins” out blood by preventing any blockage. Aspirin reduces fever and pain by inhibiting the production of prostaglandins (compounds that promote blood flow to injured sites). However, prostaglandins are very important.

Among many other things, prostaglandins produce inflammation (as mentioned above) and feelings of pain (this is to alert the body that there is something bad going on, i.e. if touching this hot pan hurts, I’m going to stop doing it). Aspirin blocks the production of prostaglandins, therefore reducing inflammation, fever and pain.

But this also means that when your immune system is attacked – say a needle pierced your skin and left behind bacteria – prostaglandins won’t be able to promote blood flow to the site. Your blood, which is thinned from the aspirin, continues to flow around your body, possibly spreading the pathogen. Reduced dilation and permeability of veins reduces the number of defense cells that can congregate at the site, destroying the infection.

Therefore, taking aspirin – as much as Will does, anyway – can potentially weaken your immune system.

Thirdly, encephalitis – an inflammation of functional tissue in the brain, caused by viral infections or a mistake in the immune system. Some of the factors in increasing potential contraction of encephalitis include a weakened immune system, an environment with mosquitos or ticks, and age. (Weakened immune system? From taking the aspirin?)

Later, we discover that Graham has autoimmune anti-NMDA encephalitis, a condition wherein the sickness stems from his body’s own destruction of NMDA receptors. Essentially, the brain works because of these things called neurons, the most specialized cells in animals (see image three. Also, the longest cell is a blue whale neuron, which can grow anywhere from ten to thirty feet long).

The neuron is the structural unit of the nervous system. Each neuron consists of a cell body that has little spider-leg like things coming out of it called dendrites. These dendrites receive signals from other cells. The cell body tapers down into a narrow axon – the longest part of the neuron. This is where the major of neuron length comes from. An electrical signal comes from another neuron to the dendrites, to the cell body, down the axon, and finally comes to terminal branches at the end of the axon, each one ending with a synaptic terminal. The synaptic terminal then attaches to another neuron’s dendrites, passing the signal on from one neuron to the next.

The neuron conveys signals through a travel of action potential; essentially, if a stimulus on the neuron reaches a certain voltage, an action potential is triggered, and a cascade of channels in the axon are opened and closed, generating varying amounts of electrical and chemical potential across the cell membrane. This potential is self-propagating, propelling itself down the axon to the synaptic terminals.

At the very end of the neuron, at the synaptic terminal, the presynaptic neuron (the neuron delivering the potential to the next neuron) must release neurotransmitters into something called the synaptic cleft, the space between the presynaptic neuron and the postsynaptic neuron (the neuron receiving the signal). As neurotransmitter molecules diffuse across the space between the two neurons, they bind to receptors in the postsynaptic membrane (see image four). This binding alters the membrane potential of the postsynaptic cell and results in a response – either inhibition or excitation.

Neurotransmitters can be chemicals like acetylcholine, serotonin, dopamine, and glutamine. A derivative of glutamine is the amino acid NMDA, which stands for N-Methyl-D-Aspartic acid. When vesicles of NMDA release NMDA into the synaptic cleft (after a signal has traveled down the length of a neuron), NMDA floats through the space between the presynaptic and postsynaptic and binds to a specific receptor – NMDA receptors.

NMDA receptors, or NMDAR, are found on the dendrites of neurons; they allow the transmission of electrical impulses from neuron to neuron. NMDA, the molecule, acts as an agonist – a molecule that binds to and activates a receptor. In the case of NMDA and NMDAR, the binding of NMDA to NMDAR triggers the opening of the receptor protein and allows for an influx of calcium and salt and an outflow of potassium. Calcium functions at a second messenger in many signaling pathways in the cell.

However, if there are no receptors, then the signal cannot be transmitted, and is lost. Destruction of these receptors, like in anti-NMDA encephalitis, causes “functions [] critical for judgement, perception of reality, human interaction, the formation and retrieval of memory, and the control of unconscious activities (such as breathing, swallowing, etc), also known as autonomic functions” to be damaged (source: Anti-NMDA).

The capacity for the nervous system to be remodeled, especially to itself – according to the tenth edition of Campbell Biology – is called neuronal plasticity. This reshaping occurs mainly at synapses and depends mainly on the amount of activity present around the synapse. Among many other things, neuronal plasticity is the cornerstone of formation and storage of memories. In turn, NMDA is the cornerstone of neuronal plasticity.

NMDA receptors are particular because they will open only if two conditions are met: a high-frequency series of action potentials in the presynaptic neuron, and these action potential arriving at the synaptic terminal at the same time that the postsynaptic cell receives a depolarizing stimulus from another synapse. In other words, the postsynaptic must simultaneously receive, from the synaptic terminal of two different presynaptic cells, a) action potentials and b) a depolarizing stimulus (see image five). The net effect results in a strengthening of action potential. Depolarizing the membrane of the postsynaptic cell raises the potential of the cell membrane from resting potential (usually a negative voltage) to the threshold. This threshold must be crossed in order for the action potential to be passed on from neuron to neuron. Essentially, the depolarizing stimulus raises membrane potential, allowing the action potential to occur.

At their resting potential, cells with NMDA receptors can allow NMDA to bind to them, but they are blocked by magnesium ions. When depolarization occurs, magnesium is realized from NMDAR and the unblocked receptors can then respond to NMDA. This allows for an influx of calcium ions and salt ions (see image six).

The particulars of NMDA receptors result in long-term potentiation, or LTP, a lasting increase in the size of the postsynaptic potentials at the synapse. This is one of the fundamental processes through which memories are stored, because LTP can last for days or weeks.  With that in mind, the destruction of these receptors creates a detrimental effect to the efficiency of storage and retrieval of memories.

In addition to memory, glutamine and NMDA play roles in schizophrenia and hallucinations. About 1% of the world suffers from schizophrenia – it’s a mental disturbance wherein the patient experiences hallucinations, delusions, and a general distorted sense of reality. Sound familiar?

Think back for a minute. Remember agonists? NMDA is an agonist for NMDA receptors; it binds to the receptor and triggers a response. In the case of NMDA, the reception results in the opening of the protein and an influx of several essential ions, like calcium. An antagonist is the counterpart of the agonist. Both agonist and antagonist bind to the NMDAR, but only the agonist triggers an efficacy. An antagonist takes the spot of the agonist and blocks the agonist from being able to bind – an example of allosteric inhibition. The antagonist has absolutely no efficacy; binding of the antagonist to the receptor results in pretty much nothing (I think).

While NMDA is the agonist for NMDA receptors, there are a multitude of antagonists for NMDA receptors as well. The street drug PCP, also known as ‘angel dust,’ is made of phencyclidine, a chemical antagonist for NMDAR. Usage of PCP induces strong schizophrenia-like symptoms. Another antagonist is ethanol, or drinking alcohol. Yes, drinking alcohol.

Dehydration, a weakened immune system that leads to his own body destroying his neuron receptors, hallucinations – almost like he’s on PCP – and a very sneaky and deceptive psychiatrist and a pushy boss. Poor Will. At least he has his dogs.

1- Blood going into the kidney, waste filtered out, blood going out of the kidney

2 - An overly complicated diagram of something that's kind of complicated, aka maintaining blood osmolarity

3 - A neuron

4

5 - A combination of postsynaptic receipts result in a greater potential (C)

6

“Does anyone have any aspirin?” – Will Graham

Sources:

http://patient.info/health/aspirin-and-other-antiplatelet-medicines

http://www.wiley.com/legacy/college/boyer/0471661791/cutting_edge/aspirin/aspirin.htm

http://www.thenakedscientists.com/forum/index.php?topic=956.0

http://www.mayoclinic.org/diseases-conditions/encephalitis/basics/risk-factors/con-20021917

http://www.antinmdafoundation.org/the-illness/what-is-anti-nmda-receptor-encephalitis/

http://www.hindawi.com/journals/tswj/2012/267120/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645546/

Revising the Consensus (JOURNYS Original Research Article on Epigenetics)

In the past it was believed that DNA was something finite and unchangeable, determining everything from your height to your intelligence to your metabolism. Recently, however, epigenetics, the study of the epigenome, has revealed that DNA can be affected by how we live and what we do.

An individual’s DNA maintains its original sequence throughout his or her life, even after epigenetic changes have affected the way the sequence is transcribed and translated. Epigenetic changes occur in many ways, but the two major mechanisms are chromatin remodeling and DNA methylation. These systems modify the function of DNA without changing its sequence [1]. But what are these changes, what causes them, and how do they help us change?

             

In the nucleus of eukaryotic cells, DNA is found wrapped around proteins for packaging and structure – this protein and DNA complex is called chromatin. The main element of this complex is a protein molecule called histones. Histone tails extend from the histone, allowing for chemical changes that are catalyzed by particular enzymes.  DNA binds to the histones in clumps so that each group of histones forms a bead-like structure called a nucleosome. The DNA holds nucleosomes together like beads on a string [2].

Chromatin remodeling is regulated by the presence of chemical modifications to these proteins. For example, the addition of chemical groups to histone tails can promote or inhibit DNA replication and transcription [3]. But while mutations in genetic information are permanent, epigenetic changes can be reversible. For example, adding acetyl groups to histone tails – histone acetylation – loosens the formation of chromatin, allowing the DNA to become more accessible and easier to transcribe. Adding methyl groups – histone methylation – brings DNA close together to inhibit transcription. Since these biochemical groups do not change the actual content of DNA, they are considered to be epigenetic changes [4].

In DNA methylation, a methyl group is added to cytosine (one of the four main bases in DNA), maintaining the condensed structure of DNA and subsequently preventing transcription [5]. Methylation is found across most of the genome in animals, with varying patterns and concentration. For example, female bee workers and the queen bee are genetically very similar, but when methyl-adding enzymes were reduced in bee larvae, all of the larvae hatched as queen bees. Therefore, the lack of methyl groups allowed special genes to be read and eventually led to the development of queen bees [6]. Out of the many epigenetic mechanisms, DNA methylation was the first discovered and the most well-researched [7].

Epigenetic processes vary in effects, from responses aiding development in the body to epigenetic changes due to pernicious conditions.

As the body matures, epigenetic factors involve themselves in the specialization of cells, in addition to helping regulate gene expression. Epigenetic changes allow for the differentiation between identical pluripotent stem cells as they develop. Even though all the cells in one body contain the exact same DNA, epigenetic processes make it possible for stem cells to differentiate – into eye cells, muscle cells or brain cells [8].

Along with responding to stimuli from inside the body, the epigenome can respond to factors from outside the body as well. The two major factors in epigenetic response to external agents are nutrition and environment. Animal studies reveal that mothers with too little methyl in their diet before childbirth can induce parts of the child’s genome to have a methyl deficiency for the rest of their lives [9]. Exposure to cigarette smoke, ionizing radiation, and pesticides can also modify epigenetic mechanisms. In vitro studies show that this exposure can result in hypomethylation, or a loss of methylation. This hypomethylation in DNA in exposed animals can be linked back to genomic instability – an increase in the likelihood of mutation in the genome [10, 11, 12]. Furthermore, genomic instability is a “driving for tumorigenesis,” the formation of cancer [13].

So epigenetic changes are influenced by a multitude of things, both natural – like cell differentiation – and pernicious – like exposure to cigarette smoke and pesticides. But can these changes be passed on?

Typically, the pattern of methyl groups attached to DNA is mostly destroyed and then reformed during the formation of gametes [2]. But some research has found that alterations in the epigenome can be passed down from generation to generation.

Mice placed under stress can pass their epigenetic changes onto their offspring. One study involved scientists exposing a parent generation of mice to the smell of cherry blossoms. Simultaneously, the mice were electrically shocked. The parents consequently associated pain with the smell of cherry blossoms. And when they had offspring, though the progeny had never been exposed to cherry blossom smell, the mice pups responded anxiously and fearfully in the presence of the smell [14]. This case and many others support the claim that epigenetic changes can be inherited from generation to generation.

Advances in the epigenetic field have paved the way for other opportunities for health improvements as well. Epigenetics is a new, albeit burgeoning, study and the elucidation of the mechanisms of epigenetic changes can be useful in many different ways. Researchers are amassing evidence that epigenetics can be involved in mental disorders [15]. And unlike genetic disorders, epigenetic changes are potentially reversible; techniques like exposure therapy are already used to help treat patients with PSTD [16].

Additionally, recent research has shown that aberrations in epigenetic mechanisms can contribute to the proliferation of malignant cells, and subsequently lead to cancer. Data from Johns Hopkins School of Medicine Center for Epigenetics in Baltimore, Maryland suggests that epigenetic changes are seen in all cancers, and the epigenome is modified in most cancer mutations [17]. With that in mind, the burgeoning field of epigenetic therapy involves drugs inhibiting enzymes that modify histones. Epigenetic therapy has been a promising new treatment for cancer [18].

As mentioned before, the differentiation of cells comes mainly from epigenetic factors. Further investigation into this mechanism promises manifold prospects in regards to the production and development of stem cells, another reason as to why studies of the epigenome can play a vital role in future medicines and treatments.

There are many positive reasons as to why the epigenome should be studied carefully – finding a cure for mental illnesses, understanding cancer, and possibly harnessing the power of stem cells. However, there are also many concerns linked to epigenetic treatments. This includes the effects of epigenetic therapy in cancer or mental illness patients unintentionally inherited by the patients’ children, and the potential for dangerous repercussions of artificially creating or inhibiting epigenetic changes.

The science of epigenetic changes and epigenetic inheritance is still in its early stages. There are many challenges being faced in the study of the epigenome; the interdisciplinary nature of the science behind the epigenome makes research difficult. Even when manipulations of epigenetic mechanisms are successful, providing evidence for the fact that an in vitro epigenetic change might have caused a particular phenotype to be present in the organism remains a quixotic notion [19]. Regardless, potentials and possibilities linked to the epigenome have already been discovered, with many more to come. 

Sources:

1. Berger, S. L., T. Kouzarides, R. Shiekhattar, and A. Shilatifard. "An Operational Definition of Epigenetics." Genes & Development 23.7 (2009): 781-83. Genes & Development. CSH Press, 2009. Web. 16 Apr. 2016. <http://data2discovery.org/dev/wp-content/uploads/2013/05/Berger-et-al.-2009-epigenetics-definition.pdf>.

 2. Reece, Jane B., and Neil A. Campbell. Campbell Biology. Boston: Benjamin Cummings / Pearson, 2011. Print.

3. Glyphis, John. "NOVA ScienceNOW: Epigenetics." PBS. PBS, Aug. 2007. Web. 15 Feb. 2016. <http://www.pbs.org/wgbh/nova/education/activities/3411_02_nsn.html#backgrou>.

4. Balogh, Peter, Dr., and Peter Engelmann, Dr. "Transdifferentiation and Regenerative Medicine." Digitális Tankönyvtár. Educatio.hu, 2011. Web. 16 Apr. 2016. <http://www.tankonyvtar.hu/en/tartalom/tamop425/0011_1A_Transzdifferenciation_en_book/ch01s03.html>.

5. "DNA Methylation." What Is Epigenetics. Whatisepigenetics.com, n.d. Web. 16 Apr. 2016. <http://www.whatisepigenetics.com/dna-methylation/>.

6. Cowell, Ian, Dr. "Epigenetics - It's Not Just Genes That Make Us." British Society for Cell Biology. N.p., n.d. Web. 9 Mar. 2016. <http://bscb.org/learning-resources/softcell-e-learning/epigenetics-its-not-just-genes-that-make-us/>.

7. "Epigenetic Modifications Regulate Gene Expression." SABiosciences. QIAGEN, 2010. Web. 16 Apr. 2016. <http://www.sabiosciences.com/pathwaymagazine/pathways8/epigenetic-modifications-regulate-gene-expression.php>.

8. "Epigenetics for Health and Disease." Crg.eu. Centre for Genomic Regulation, 11 May 2011. Web. 16 Apr. 2016. <http://www.crg.eu/en/news/epigenetics-health-and-disease>.

9. "Nutrition and the Epigenome." Learn.Genetics. Genetic Science Learning Center, 22 June 2014. Web.

16 Apr. 2016. <http://learn.genetics.utah.edu/content/epigenetics/nutrition/>.

10. Knopik, Valerie S., Matthew A. Maccani, Sarah Francazio, and John E. McGeary. "The Epigenetics of Maternal Cigarette Smoking During Pregnancy and Effects on Child Development." Development and Psychopathology. U.S. National Library of Medicine, Nov. 2012. Web. 16 Apr. 2016. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581096/>.

11. Merrifield, Matt, and Olga Kovalchuk. "Epigenetics in Radiation Biology: A New Research Frontier." Frontiers in Genetics. Frontiers Media S.A., 4 Apr. 2013. Web. 16 Apr. 2016. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616258/>.

12. Collotta, M., P. A. Bertazzi, and V. Bollati. "Epigenetics and Pesticides." National Center for Biotechnology Information. U.S. National Library of Medicine, 10 May 2016. Web. 22 Feb. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/23380243>.

13. Shen, Z. "Genomic Instability and Cancer: An Introduction." National Center for Biotechnology Information. U.S. National Library of Medicine, Feb. 2011. Web. 8 Feb. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/21278445>.

14. Kim, Meeri. "Study Finds That Fear Can Travel Quickly through Generations of Mice      DNA." Washington Post. The Washington Post, 7 Dec. 2013. Web. 16 Feb. 2016. <https://www.washingtonpost.com/national/health-science/study-finds-that-fear-can-travel-quickly-through-generations-of-mice-dna/2013/12/07/94dc97f2-5e8e-11e3-bc56-c6ca94801fac_story.html>.

15. Schmidt, U., F. Holsboer, and T. Rein. "Epigenetic Aspects of Posttraumatic Stress Disorder." National Center for Biotechnology Information. U.S. National Library of Medicine, 2011. Web. 15 Feb. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/21508512>.

16. "Prolonged Exposure Therapy." PTSD: National Center for PTSD. U.S. Department of Veterans Affairs, 14 Aug. 2015. Web. 16 Feb. 2016. <http://www.ptsd.va.gov/public/treatment/therapy med/prolonged-exposure-therapy.asp>.

17. Taylor, Ashley. "Epigenetic Changes Can Cause Cancer." TheScientist. N.p., 25 July 2015. Web. 16 Apr. 2016. <http://www.the-scientist.com/?articles.view/articleNo/40592/title/Epigenetic Changes-Can-Cause-Cancer/>.

18. Sharma, Shikhar, Theresa K. Kelly, and Peter A. Jones. "Epigenetics in Cancer." Carcinogenesis: Oxford Journal. Oxford University Press, 13 Sept. 2009. Web. 16 Apr. 2016. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802667/>.

19. Bohacek, Johannes, and Isabelle M. Mansuy. "Epigenetic Inheritance of Disease and Disease Risk." Neuropsychopharmacology. 2016 American College of Neuropsychopharmacology, 8 May 2012. Web. 16 Apr. 2016. <http://www.nature.com/npp/journal/v38/n1/full/npp2012110a.html>.

The Theory of Everything (Review of ‘The Accidental Universe’ by Alan Lightman)

In the first of his essays about the universe, The Accidental Universe, Alan Lightman reflects upon the miniscule probabilities of life emerging within the universe. There are specific parameters that must be met for life to be able to exist – there cannot be too much nor too little dark matter in the universe (because the universe would expand too fast or too slow respectively), there cannot be too much nor too little distance between the prospective planet and its sun, there cannot too much nor too little force within the nucleus of an atom, and so on and so forth.

Some use this probability to prove the existence of God – how can our universe exist? The chances of life emerging in a universe are so infinitesimal, how can there not be a God?  And there are others, Steven Hawking among them, who believe there are an infinite number of universes, combining together in a number of alternate universes, creating something called the multiverse.

While some believe that alternate universes can portray the differences between the two paths forming the fork in the road – in one universe, I could’ve become a ballet dancer, and in another, a world-renowned pianist – physicists believe that each alternate universe has varying fundamental properties. In one universe, there is a slightly larger amount of dark matter (larger than ours) and the universe accelerated so quickly in its early stages that matter couldn’t congregate to form stars. In another universe, the nuclear force is slightly stronger than it is in our universe, and all of the hydrogen atoms in that other infant universe would’ve merged with other hydrogen atoms to make helium, leaving no hydrogen and subsequently eliminating water from the universe completely.

In the theory of the multiverse, our universe just happens to be the one where the amount of dark matter is just right, the nuclear force and the distance between Earth and the sun slides right into the parameters that life can grow within.

If that is the case, Lightman postulates, then search for the theory of everything – the mission of every physicist to describe all of the properties of the universe – is meaningless. The properties of our universe simply are. You are here. I am here. Humans are here in this universe because the properties permit life to exist. This means that our universe is one in an infinite amount of others. According to Lightman, “the basic properties of our universe are accidental and incalculable. In addition, we must believe in the existence of many other universes. But we have no conceivable way of observing these other universes and cannot prove their existence. Thus, to explain what we see in the world and in our mental deductions, we must believe in what we cannot prove,” which Lightman furthers in his third essay, The Spiritual Universe.

From Beast to Bronze (Research & Thoughts on the Animal Sculptures of Arthur Putnam)

In the San Diego Museum of Art, on the right wing of the base floor is a gallery entitled Ferocious Bronze, a collection of cire-perdue sculptures of pumas, tigers, lions, horses, and other animals, their movements stilled within their bronze molds. The dark, aged-bronze stands out against the sharp yellow walls, and the overhead lights throw distorted shadows onto the floor.

The jaws of each puma are wide and gaping, claws extended and muscles rippling. How were these sculptures made? And how did Arthur Putnam capture the essence of these animals so vividly? Although the sculptures are not smooth in texture and the features of the beasts are rough, the tension of the joints and the limbs of the pumas portray a sense of motion. The eye of the observer is drawn from a snarling maw to the sloping of a spine to the sharp curve of claws. In all, the sculptures portray a sense of carnality and rawness.

Putnam never received formal education in the arts – he had the most basic instruction in drawing techniques then drew from his own innate ability to sculpt and to transform, preserving the most constituent qualities of blood and bone to bronze. Even after Putnam became successful enough to travel to Europe, he didn’t travel to receive an education; instead, he sought out a visual experience.

In San Diego, Putnam was notorious in the zoo, where he would draw animals, and in the wild as well. While his lack of a formal education in the arts leaves his sculptures less polished and precise than his contemporaries, Putnam’s sculptures are visceral and raw.

Cire perdue, French for lost wax, was the process that Putnam used to create his metal sculptures. Cire perdue is a long and arduous process, but the resulting sculpture retains the finer details in the sculptor’s original model.

The process begins when a model is made of wax or clay. Putnam began by creating a crude, wire skeleton – four legs, a head, and a tail. Clay is molded around the skeleton. The model is then sectioned off; each section has its own plaster mold made. After assembling the molds, the sculptor casts a thin shell of the sculpture in wax. On top of the wax is comes a ceramic mold – the bottom layer is plaster mold, then wax, then ceramic mold. After pouring wax out of the mold, molten bronze takes its place. The layers are now plaster mold, bronze, ceramic mold. Then when the bronze solidifies, the mold is cracked open, revealing the finished bronze sculpture. Any remaining imperfections are removed by chasing – filing and polishing. The bronze is finished with a torch while applying a chemical to create a patina – a surface tone.

The sculptures of Arthur Putnam are lively and ragged with an animalistic kind of edge. But why pumas? Why lions and snakes and horses and, in some of his sculptures, man? The creatures that Putnam chose to depict were muscular, toned, and noble. There was something extremely attractive to Putnam in the rawness of each creature. To him, there was beauty in their roughness, a characteristic evident in his work.

Sources:

http://jacklondontablet.com/biography.htm

https://americansculptors.wordpress.com/2011/06/16/arthur-putnam/

http://www.sdmart.org/art/exhibit/ferocious-bronze

The Invisible City (Research & Thoughts on Dadaab’s Refugee Camp)

In the film Jurassic Park, there is a scene wherein Tyrannosaurus Rex attempts to kill a group of humans. A doctor calls out, “Don’t move! He can’t see you if you don’t move!” While the scientific accuracy of this statement is dubious, it is interesting when applied to life, human attention, and social media.

A little more than sixty miles from the western border of Somalia – into its neighboring country, Kenya – lies a town with a population the size of Minneapolis. Its residents? Refugees from Somalia who fled from war in their homeland.

The camp was first set up in 1992 and has grown to house more than 350,000 permanent residents. Lately, with Europe struggling with an influx Syrian refugees, Dadaab has been forgotten. How can the largest refugee camp in the world be forgotten?

The United Nations Refugee Agency has worked to supply Dadaab with resources and recently the German minister has paid a visit to Dadaab, but deforestation has left Dadaab with little to no resources, making the refugee camp prone to illnesses, like the cholera epidemic in January of 2016.

But even with the assistance from other countries and the UN, Dadaab has slipped from the media’s attention. Why?

Refugees have lived in Dadaab for almost twenty-five years. Some children born in the camp have known nothing but the red sand and thorned fences their whole lives. How has the problem not been solved?

The Kenyan government tolerates the existence of Dadaab, but only just. More than often, Dadaab is used as a scapegoat, to blame for terrorist attacks unrelated to the refugees.

Three-hundred and fifty thousand people. Dilapidated huts covered with plastic, squatting in the sand, forming rows upon rows of makeshift homes. Twenty-five years. The largest refugee camp in the world. Dadaab.

Why is it that nobody knows? When I learned of Dadaab, I was shocked to discover that such a place existed. How could a city become so invisible to mainstream media? And I’m sure that there are many other horrible things going on in the world that I have no idea of.

Is it because their existence is a peaceful one? In a country across the globe, in a remote city, in the middle of a red and sandy landscape that offers nothing but rock and poor soil, lies a city – unmoving – but very much alive. We focus on things that move, that are violent, that affect us. Dadaab’s lack of appearance in the news and media reflects upon the very nature of human attention.



Sources:

http://www.cartographie.ird.fr/publi/Refugies/Final_report.pdf

http://www.latimes.com/books/la-ca-jc-ben-rawlence-20160103-story.html

http://www.theguardian.com/global-development-professionals-network/2016/feb/01/dadaab-somalia-home-cannot-leave-refugees

http://www.npr.org/sections/goatsandsoda/2016/01/11/462698276/the-worlds-largest-refugee-camp-looks-like-a-slum-from-star-wars

http://data.unhcr.org/horn-of-africa/region.php?id=3

http://www.cnn.com/interactive/2015/10/world/dadaab-refugees/

An Unhealthy Obsession (Thoughts on the Obsession with Calories and Body-Image)

As a tutor at my local library, I often see students coming in and carrying boxes of things to sell for fundraising purposes – cookies, cookie dough, buffet tickets et cetera. One day I happened to be tutoring a young girl who was selling bars of chocolate. She asked if I could buy one to support her cause and I agreed.

“What flavors do you have?” I had asked.

“Lots!” she answered, and indeed, as she opened her box, inside were five to six varieties of milk and dark chocolate.

I chose a caramel milk-chocolate bar.

“Those are good,” she had said, “But watch out. Those are two-hundred calories!”

At first, I wondered if she told the nutritional values of each chocolate bar to her customers. Then I wondered if I looked as though I needed to be counting calories. Then I remembered that the previous week, she had shown me a mobile app called MyFitnessPal, an online diary used to log the amount of calories burned and consumed every day.

My student was only in middle school, but already, she was logging down how many calories every piece of food she ingested was. Many menus in restaurants, bakeries and coffee shops now boast a nutritional value next to each item. Is this another way for our society to impose beauty standards on individuals? Or is it simply a decision meant to inform curious customers?

Either way, there are many ideal body types – the quixotic figure varies from country to country, and era to era.

In the year 28,000 BCE, humanoids carved a small statuette, depicting a female figure with grotesquely exaggerated features, corpulent and bulging. Some think that the Woman of Willendorf depicts the ideal body type in that time. In many ancient African societies, rolls of fat were beautiful, since they represented wealth and an abundance of food. In the year 1501, Michelangelo carved a marble sculpture of the biblical figure David, depicting a strong and youthful individual with taut muscles.

From the mathematical proportions in da Vinci’s Vitruvian man to the rigid lines of ancient Egyptian depictions of pharaohs, it is clear that ideal body types have changed as time passes. Even today, society portrays the ideal figure in everything from books and literature to billboard advertisements to commercials.

A Matter of Circumstance (Review & Research on “A Sound of Thunder” and the Side-Effects of Time Travel)

The year is 2055. Time travel has been invented, but the nature of this new advancement is used more for entertainment purposes than everything; the wealthy use time travel to transport themselves to the past and kill for sport. The game? Dinosaurs.

One man decides to go back and hunt dinosaurs for the first time in his life. Before the group leaves, they discuss how a fascist presidential candidate was defeated by a much better one, to everyone’s relief.

As they begin the tour, the tour guide reminds everyone to only kill the dinosaurs with the special tags, and to stay on the path at all times. These precautions serve to minimize the changes that the hunters will leave on their timeline. As Ray Bradbury explains it, a “small thing [] could upset balances and knock down a line of small dominoes and then big dominoes and then gigantic dominoes, all down the years across Time,” creating an enormous impact from one small incident (Bradbury).

The man arrives in the Jurassic time period. The T-Rex that they wish to kill has been observed by the tour guide before – the death of the T-Rex is very close to when the hunters will kill him, so the death will not largely impact their timeline. All the tagged dinosaurs would’ve died within minutes without the hunters, so their death was inevitable anyway.

The man hears the roar of the T-Rex. Frightened, he accidentally steps off the path. Immediately, the tour guide yells at him to get off, to return to the time machine.

The tour guide is very upset, and barely lets the man return with them to the future. As they arrive in the lobby of the time travel company, they notice that the air smells strange. The words on the wall are slightly different. Quickly, they ask the receptionist who won the election, to which he replies, “Deutscher of course!” who was the fascist candidate. The man who stepped off the path looks down at his boot in horror. Underneath his boot is a single butterfly. He hears the sound of thunder, then dies as the tour guide shoots him.

Although the ending is rather abrupt, Ray Bradbury’s A Sound of Thunder explores several ideas.

First of which, the chaos theory. A study in initial events and how essential they are in dynamic systems, commonly referred to as the butterfly effect. The butterfly on the bottom of the man’s boot is Bradbury’s nod to this theory – that very simple events can have profound and complex effects. The man steps on a butterfly and thousands of years later, a dictator has won America’ presidential election and the English language is forever changed.

Secondly, the danger associated with time travel. The human immune system works in two ways: innate immunity – general defenses that the body is born with, including inflammatory responses, fever, and other symptoms of the common cold; adaptive immunity – a specific kind of defense that responds to the pathogen that has made its way into an individual’s system. Adaptive immunity is unique in the way that there are first and secondary adaptive immunity responses. The first time a pathogen is detected, the body produces cells specific to destroying that pathogen. However, these cells will then proliferate into memory cells. The second time there is an exposure, the body (specifically, the memory cells) elicit a secondary immune response that is more rapid and more intense than the first immune response. This is immunological memory.

The Greek historian Thucydides observed that victims of the plague who had recovered could then tend to others with the disease, “for the same man was never attacked twice” (MIT). In regards to time travel, transporting to a different time period would expose the traveler to numerous diseases that they had never been exposed to before. Immunological memory serves as the cornerstone of the human immune system. Time travelers’ immune systems would be responding with the slower, weaker immune response to new pathogens. In her novel, The Time Traveler’s Wife, Audrey Niffenegger even portrays time travel as a disease itself.

And thirdly, the theory of the multiverse. Originally conceived by the physicist Hugh Everett, the theory suggests that there are an infinite number of universes, each one slightly different from the next, resulting from the infinite possible ways a decision or a choice can affect a timeline. Physicist David Deutsch wrote that “if time travel to the past were indeed possible, the many worlds scenario would result in a time traveler ending up in a different branch of history than the one he departed from” (New Dawn). Does this mean that, in some alternate universe, the man in A Sound of Thunder never stepped on the butterfly? And in another, he was left behind in the Jurassic time period? Or another where he never went time traveling in the first place.

Did the man return to a different universe than the one he left? Or did his actions impact his timeline, the same universe he left? Parallel universes open up thousands of possibilities, side-stepping paradox limitations by allowing travelers to hop from universe to alternate universe. However, the ideas are all hypothetical – the basis of all these theories and stories stems from time travel, something we’ve yet to discover.

Sources:

A Sound of Thunder, Ray Bradbury.

http://www.newdawnmagazine.com/articles/time-travel-the-multiverse-many-worlds-many-timelines

http://classics.mit.edu/Thucydides/pelopwar.2.second.html

More than Meets the Eye (JOURNYS Original Research Article on Sleep Published in Volume 7, Issue 1)

More Than Meets the Eye

Sleep is a mysterious and bizarre concept that has puzzled many people for centuries. Why do our bodies spend so much time inefficiently when we sleep? Yes, we need sleep to function, but what are our bodies really doing? Does our body just replenish energy during the precious time we spend asleep?

During one night, our bodies transition through four stages and two types of sleep. The four stages occur in cycles and the two types of sleep are NREM (non-rapid eye movement) sleep and REM (rapid eye movement) sleep. As we fall into unconsciousness, our bodies begin the sleep cycle with Stage 1. Stage 1 normally lasts five to ten minutes and is the transition between consciousness and sleep. It is also the stage where one may experience hallucinations, the feeling of falling, or floating weightlessly. The brain will begin to produce sleep spindles during Stage 2, which are rapid, rhythmic brain waves.¹ Stage 2 lasts for about 20 minutes, during which body temperature decreases and heart rate begins to slow. Following Stage 2 is delta sleep, or Stage 3. Here the brain starts to produce deep, slow brain waves called delta waves – hence the name of Stage 3. As Stage 1 was the transitional period between consciousness and sleep, Stage 3 is the transitional period between light sleep and deep sleep. Up until the end of Stage 3, our bodies have been in NREM sleep. As Stage 3 concludes, the body begins to enter REM sleep.² REM sleep characteristics can include the fluttering of eyes under the eyelids, irregular and shallow breathing, and loss of muscle control. REM sleep occurs about an hour after one first falls asleep and is also called Stage 4. The body is still and relaxed, save for a few occasional twitches, and blood pressure rises. This is also the stage in which dreaming will occur.³

The structure of sleep follows a pattern alternating between NREM sleep and REM sleep. The body usually goes through Stage 1 once throughout the night, passing through Stages 2 and 3 and finally entering REM sleep. After about 10 minutes of REM sleep, the body will return to Stage 2 and repeat this cycle throughout the night. The first time your body enters REM sleep, the stage will only last about ten minutes but by the end of the night, the last cycle of REM sleep can be up to 60 minutes long. For every cycle of sleep the body experiences, the length of REM sleep will increase while the length of delta sleep will decrease. By the end of the night, there is almost no delta sleep left in the cycle. Each cycle takes approximately 90 minutes and the body will go through the cycle of stages four to five times a night. When you awaken naturally, you will have just finished a period of REM sleep.¹

Sleep is vital to human health. When our bodies fall into unconsciousness, they do a lot more than what it looks like they’re doing. Although it doesn’t seem like it, the amount of energy consumed by the brain does not decrease when the body enters sleep, primarily because of several systems in the brain active during sleep.

The first is a system that flushes waste from the brain. During consciousness, by-products of neural activity build up and every night sleep clears this build up. Since the brain is enclosed by a set of molecular gateways – the blood-brain barrier – the system that clears waste in the body does not extend to the brain. During sleep, cerebral spinal fluid (CSF) is pumped through the brain’s tissue and the waste is then flushed back into the circulatory system where it eventually works its way to the liver. As this system cleans the brain, brain cells shrink to allow CSF to flow more smoothly through tissue. This system is called the glymphatic system and is ten times more active during sleep versus consciousness.⁴

Another active region of the brain during sleep is waves produced during different stages of sleep. These different waves are characterized by frequencies corresponding to the nature of the stage it is released in. These waves show the amount of activity in the brain and our level of consciousness.

In Stage 1 and REM sleep, the brain produces theta waves which are usually measured at 4 to 7.5 cycles per second, or 4 to 7.5 hertz. These waves are also experienced during deep meditation. Theta state heightens receptivity and can be produced fleeting as the body wakes or falls asleep. In addition, during REM sleep, the brainstem blocks information from leaving the brain’s motor cortex so your muscles are relaxed and unmoving.⁵ Throughout Stage 2, sleep spindles will occur periodically as they are rhythmic waves and unvarying in form. The sleep spindles are measured between 10 and 14 hertz.⁶ In Stage 3, delta waves are produced. Their frequency ranges from 0 hertz to 4 hertz and they are the lowest set of frequencies a human brain will experience. Certain frequencies of delta waves trigger the release of growth hormone and are essential to the restorative process of sleep.⁵ These active portions of the brain during sleep contribute to the remedial nature of sleep. This means that our time sleeping is absolutely critical to our performance; the human body is actively working and cleansing itself when we are not aware.

              Throughout a night of sleep, dreams are perhaps the most least understood stage of unconsciousness. What are their purposes and what do they mean? Although there are no solid facts on the purposes of dreams, there are many theories as to why dreaming occurs.

              Dr. J. Allan Hobson, a psychiatrist and sleep researcher, believes that since we always wake after a period of REM sleep, dreaming is a way for the brain to “warm-up”. In dreams we anticipate the emotions, sights and sounds we’ll experience upon waking up. In this sense, dreams prepare our bodies to return to consciousness.⁷

              Another theory comes from Carl Jung, who believed that dreams are meant to recompense for the parts of our personality that are less developed when we are awake. However, a contradicting theory is claimed by Calvin Hall, who studied 2 week journals from test subjects. Hall states that dreams are continuous with ideas and behavior when we are awake.⁸ Even still, there are more opinions and arguments over what dreams are meant to do. A Nobel laureate named Francis Crick believed dreams were a way for the brain to discard bits and pieces of memories that were deemed irrelevant. Crick theorized that dreams were the accumulation of excess thoughts and ideas that didn’t make it into the brain’s memory.⁹ Thus, the reason why we hardly ever remember our dreams.

              To this day, scientists and experts still debate over the meaning of dreams, but across the controversy, all sides of the debate can agree that everyone has dreams – although most people forget them by the end of the night.

              At a glance, the mechanics of sleep seem simple: four stages of sleep and dreaming in between. However, with a closer look sleep is intricately complex and much more than meets the eye. This time that we spend asleep is not just our body lying around doing nothing - our bodies use the same amount of energy during asleep as consciousness, and sleep is just as complicated as being awake. Even today, extensive knowledge on sleep is not known, but every day experts learn more and more.

Bibliography

1. Russo, Michael. "Sleep: Understanding the Basics Causes, Symptoms, Treatment - Stages of Sleep." EMedicineHealth. Web. 14 Jan. 2015. 

2.  "What Happens When You Sleep?" National Sleep Foundation. Web. 8 Dec. 2014.   

3. Dement, W., and N. Kleitman. "Cyclic Variations In EEG During Sleep And Their Relation To Eye     Movements, Body Motility, And Dreaming." Electroencephalography and Clinical        Neurophysiology 9.4 (2003): 673-90. ScienceDirect. Web. 14 Jan. 2015.  

4. Iliff, Jeffrey, Minghuan Wang, et al. "A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β." National Center for Biotechnology Information. U.S. National Library of Medicine, 15 Aug. 2012. Web. 14 Jan. 2015.

5.  "The Four Brain States." Tools for Wellness. Web. 14 Jan. 2015.              

6.  Lüthi, A. "Sleep Spindles: Where They Come From, What They Do." National Center for         Biotechnology Information. U.S. National Library of Medicine, 27 Aug. 2013. Web. 14 Jan. 2015.

7. Hobson, J. Allan. "REM Sleep And Dreaming: Towards A Theory Of Protoconsciousness." Nature     Reviews Neuroscience (2009): 803-13. Nature Review Neuroscience. Web. 14 Jan. 2015.

8. Domhoff, G. William. "The Purpose of Dreams." DreamResearch.net. Web. 14 Jan. 2015.

9. Breecher, Maury. "The Biology of Dreaming: A Controversy That Won't Go to Sleep." Columbia University. Web. 14 Jan. 2015.