Mastering Mega Minds: Our Quest for Cognitive Development

Catalyst Volume 9

Humans are continuously pursuing perfection. This drive is what motivates scientific researchers and comic book authors to dream about the invention of bionic men. It seems inevitable that this quest has expanded to target humankind’s most prized possession: our brain. Cognitive enhancements are various technologies created in order to elevate human mental capacities. However, as scientists and entrepreneurs attempt to research and develop cognitive enhancements, society faces an ethical dilemma. Policy must help create a balance, maximizing the benefits of augmented mental processing while minimizing potential risks.

Cognitive enhancements are becoming increasingly prevalent and exist in numerous forms, from genetic engineering to brain stimulation devices to cognition-enhancing drugs. The vast differences between these categories make it difficult to generalize a single proposition that can effectively regulate enhancements as a whole. Overall, out of these types, prescription pills and stimulation devices currently have the largest potential for widespread usage.

Prescription pills exemplify the many benefits and drawbacks of using cognitive enhancements. ADHD medications like Ritalin and Adderall, which stimulate dopamine and norepinephrine activity in the brain, may be the most ubiquitous example of available cognitive enhancements. These drugs are especially abused among college students, who use these pills to stay awake for longer periods of time and enhance their attention while studying. In a collection of studies, 4.1 to 10.8% of American college students reported recreationally using a prescription stimulant in the past year, while the College Life Study determined that up to a quarter of undergraduates used stimulants at least once during college.^1,2 Students may not know or may disregard the fact that prolonged abuse has resulted in serious health concerns, including cardiopulmonary issues and addiction. When these medications are taken incorrectly, especially in conjunction with alcohol, users risk seizures and death.³

In addition to stimulants, there are a variety of other prescriptions that have been shown to improve cognitive function. Amphetamines affect neurotransmitters in the brain to increase consciousness and adjust sleep patterns. They achieve this by preventing dopamine reuptake and disrupting normal vesicular packaging, which also increases dopamine concentration in the synaptic cleft through reverse transport from the cytosol.⁴ These drugs are currently used by the armed forces to mitigate pilots’ fatigue in high-intensity situations. While usage of these drugs may help regulate pilots’ energy levels, this unfortunately means that pilots face heavy pressure to take amphetamines despite the possibility of addiction and the lack of approval from the U.S. Food and Drug Administration.⁵

Besides prescription medications, various technological devices exist or are being created that affect cognition. For instance, transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are devices currently marketed to enhance cognitive functioning through online websites and non-medical clinics, even though they have not yet received comprehensive clinical evaluations for this purpose.⁶ tDCS works by placing electrodes on the scalp to target specific brain areas. The machine sends a small direct current through electrodes to stimulate or inhibit neuronal activity. Similarly, TMS uses magnetic fields to alter neural activity. These methods have been shown to improve cognitive abilities including working memory, attention, language, and decision-making. Though these improvements are generally short-term, one University of Oxford study used tDCS to produce long-term improvements in mathematical abilities. Researchers taught subjects a new numerical system and then tested their ability to process and map the numbers into space. Subjects who received tDCS stimulation to the posterior parietal cortex displayed increased performance and consistency up to six to seven months after the treatment. This evidence indicates that tDCS can be used for the development of mathematical abilities as well as the treatment of degenerative neurological disorders such as Alzheimer’s.⁷

Regulation of cognitive enhancements is a multifaceted issue for which the risks and benefits of widespread usage must be intensively examined. According to one perspective, enhancements possess the ability to maximize human efficiency. If an enhancement can enable the acceleration of technological development and enable individuals to solve issues that affect society, it could improve the quality of life for users and non-users alike. This is why bans on anabolic steroids are not directly comparable to those on cognitive enhancements. While both medications share the goal of helping humans accomplish tasks beyond their natural capabilities, cognitive enhancements could accelerate technological and societal advancement. This would be more beneficial to society than one individual’s enhanced physical prowess.

While discussing this, it should be noted that such enhancements will not instantaneously bestow the user with Einsteinian intellectual capabilities. In a recent meta-analysis of 48 academic studies with 1,409 participants, prescription stimulants were found to improve delayed working memory but only had modest effects on inhibitory control and short-term episodic memory. The report also discussed how in some situations, other methods, including getting adequate sleep and using cognitive techniques like mnemonics, are far more beneficial than taking drugs such as methylphenidate and amphetamines. Biomedical enhancements, however, have broad effects that are applicable to many situations, while traditional cognitive techniques that don’t directly change the biology behind neural processes are task-specific and only rarely produce significant improvements.⁸

However, if we allow enhancement use to grow unchecked, an extreme possibility is the creation of a dystopian society led by only those wealthy enough to afford cognitive enhancements. Speculation about other negative societal effects is endless; for example, widespread use of cognitive enhancements could create a cutthroat work environment with constant pressure to use prescription pills or cranial stimulation, despite side effects and cost, in order to compete in the job market.

The possibility of addiction to cognitive enhancements and issues of social stratification based on access or cost should not be disregarded. However, there are many proposed solutions to these issues. Possible governmental regulation proposed by neuroethics researchers includes ensuring that cognitive enhancements are not readily available and are only given to those who demonstrate knowledge of the risks and responsible use of such enhancements. Additionally, the creation of a national database, similar to the current system used to regulate addictive pain relievers, would also help control the amount of medication prescribed to individuals. This database could be an integrated system that allows doctors to view patients’ other prescriptions, ensuring that those who attempt to deceive s pharmacies to obtain medications for personal abuse or illegal resale could not easily abuse the system. Finally, to address the issue of potential social inequality, researchers at Oxford University’s Future of Humanity Institute proposed a system in which the government could support broad development, competition, public understanding, a price ceiling, and even subsidized access for disadvantaged groups, leading to greater equalized access to cognitive enhancements.⁹

Advancements have made it possible to alter our minds using medical technology. Society requires balance to regulate these enhancements, an environment that will promote safe use while preventing abuse. The regulation of cognitive enhancement technologies should occur at several levels to be effective, from market approval to individual use. When creating these laws, research should not be limited because that could inhibit the discovery of possible cures to cognitive disorders. Instead, the neuroethics community should focus on safety and public usage regulations with the mission of preventing abuse and social stratification. Cognitive enhancements have the potential to affect the ways we learn, work, and live. However, specific regulations to address the risks and implications of this growing technology are required; otherwise the results could be devastating.

References

1. McCabe, S.E. et al. J. Psychoactive Drugs 2006, 38, 43-56.
2. Arria, A.M. et al. Subst. Abus. 2008, 29(4), 19-38.
3. Morton, W.A.; Stockton, G. J. Clin. Psychiatry 2000, 2(5), 159-164.
4. España, R.; Scammel, T. SLEEP 2011, 34(7), 845-858.
5. Rasmussen, N. Am. J. Public Health 2008, 98(6), 974-985.
6. Maslen, H. et al. J. of Law and Biosci. 2014, 1, 68-93.
7. Kadosh, R.C. et al. Curr. Biol. 2010, 20, 2016-2020.
8. Ilieva, I.P. et al. J. Cogn. Neurosci. 2015, 1069-1089.
9. Bostrom, N.; Sandberg, A. Sci. Eng. Ethics 2009, 15, 311-341.

Defect Patch: The Band-Aid for the Heart

Catalyst Volume 9

Imagine hearing that your newborn, only a few minutes out of womb, has a heart defect and will only live a couple more days. Shockingly, 1 in every 125 babies is born with some type of con-genital heart defect, drastically reducing his or her lifespan.¹ However, research institutes and hospitals nationwide are testing solutions and advanced devices to treat this condition. The most promising approach is the defect patch, in which scaffolds of tissue are engineered to mimic a healthy heart. The heart is enormously complex; mimicking is easier said than done. These patches require a tensile strength (for the heart’s pulses and variances) that is greater than that of the left ventricle of the human.¹ To add to the difficulty of creating such a device, layers of the patch have to be not only tense and strong, but also soft and supple, as cardiac cells prefer mal-leable tissue environments.

Researchers have taken on this challenge and, through testing various biomaterials, have de-termined the compatibility of each material within the patch. The materials are judged on the ba-sis of their biocompatibility, biodegradable nature, reabsorption, strength, and shapeability.² Natural possibilities include gelatin, chitosan, fibrin, and submucosa.¹ Though gelatin is easily biode-gradable, it has poor strength and lacks cell surface adhesion properties. Similarly, fibrin binds to different receptors, but with weak compression.³ On the artificial side, the polyglycolic acid (PGA) polymer, is strong and porous, while the poly lactic co-glycolic acid (PLGA) polymer has regulated biological properties, but poor cell attachment. This trade-off between different components of a good patch is what makes the building and modification of these systems so difficult. Nevertheless, the future of defect patches is extremely promising.

An unnatural polymer that is often used in creating patches is polycaprolactone, or PCL. This material is covered with gelatin-chitosan hydrogel to form a hydrophilic (water-conducive) patch.¹ In the process of making the patch, many different solutions of PCL matrices are pre-pared. The tension of the patch is measured to make sure that it will not rip or become damaged due to increased heart rate as the child develops. The force of the patch must always be greater than that of the left ventricle to ensure that the patch and the heart muscles do not rupture.¹ Although many considerations must be accounted for in making this artificial patch, the malleability and adhesive strength of the device are the most important.¹ Imagine a 12-year-old child with a defect patch implanted in the heart. Suppose this child attempts to do a cardio workout, including 100 jumping jacks, a few laps around a track, and some pushups. The heart patch must be able to reach the ultimate tensile strain under stress without detaching or bursting. The PCL core of the patch must also be able to handle large bursts of activity. Finally, the patch must be able to grow with the child and the heart must be able to grow new cells around the patch. In summary, the PCL patch must be biodegradable, have sufficient mechanical strength, and remain viable under harsh conditions.

While artificial materials like PCL are effective, in some situations, the aforementioned design criteria are best fulfilled by patches made from natural biomaterials. For instance, chitosan serves as a good template for the outside portion of the patch.⁴ This material is biocompatible, bioabsorbable, and shapeable. Using natural materials can reduce the risk of vascularization, or the abnormal formation of blood vessels. They can also adapt to gradual changes of the heart. Natural patches being developed and tested in Dr. Jeffrey Jacot’s lab at Rice University include a core of stem cells, which can differentiate into more specialized cells as the heart grows. They currently contain amniotic fluid-derived stem cells (AFSC) which must be isolated from hu-mans.⁵ Researchers prepare a layer of chitosan (or fibrin in some cases) and polyethylene gly-col hydrogels to compose the outside part of the patch.⁴ They then inject AFSC into this matrix to form the final patch. The efficiency of the patch is measured by recording the stem cells’ ability to transform into new cells. In experiments, AFSC are able to differentiate into virtually any cell type, and are particularly promising in regenerative medicine.⁵ These initial prototypes are still being developed and thoroughly tested on rodents.⁶ A major limitation of this approach is the ina-bility of patches to adapt in rapidly developing hearts, such as those of human infants and patch testing on humans or even larger mammals has yet to be done. The most important challenges for the future of defect patches are flexibility and adaptability.⁶ After all, this patch is essentially a transformed and repaired body part. Through the work of labs like Dr. Jacot’s, cardiac defects in infants and children may be completely treatable with a patch. Hopefully, in the future, babies with this “Band-Aid” may have more than a few weeks to live, if not an entire lifetime.

References

1. Pok, S., et al., ACS Nano. 2014, 9822–9832.
2. Pok, S., et al., Acta Biomaterialia. 5630–5642.
3. Pok, S., et al., Journal of Cardiovascular Translational Research J. of Cardiovasc. Trans. Res. 2011, 646–654.
4. Tottey, S., Johnson, et al. Biomaterials. 2011, 32(1), 128– 136.
5. Benavides, O. M., et al., Tissue Engineering Part A. 1185–1194.
6. Pok, S., et al., Tissue Engineering Part A. 1877–1887.

Microglia: Gardeners with Guns

Catalyst Volume 9

If you ask anyone about the brain, their response will almost certainly involve neurons. Although neurons have been the stars of neuroscience for the past hundred years, the brain would be entirely dysfunctional if not for the variety of brain support cells, collectively known as glia.¹

Glial cells serve a variety of purposes in the central nervous system. Oligodendrocytes produce an insulating fatty-material called myelin, and astrocytes maintain electrical impulses in the neuronal network.¹ Perhaps the least glorious of glial functions are carried out by the microglia, which are the neurological equivalent of your household gardeners: pruning unwanted synapses and tending to the new ones. However, microglia are the first line of immune defense in the brain. From the brain’s humble beginnings as a mass of undifferentiated neurons to its affliction with the weeds of old age, microglia are tasked with neuronal maintenance and repair, meaning that deviation from their “just-right” activity can cause a variety of neural diseases. Too little activity, and one can be autistic or schizophrenic; too much activity, and one may be afflicted with Alzheimer’s or Parkinson’s. Given the large role these tiny cells play in brain protection, therapies that regulate microglial activation could be the key to curing a slew of neurological disorders.

Microglia respond to neural stress and injury through different mechanisms unique to their respective cell types: amoeboid phagocytic, resting ramified, and activated.² Amoeboid phagocytic glia act similarly to other scavengers and ingest large amounts of cellular debris in the developing brain during gestation.³ In postnatal development, these glia transform into resting ramified glia, which remain semi-dormant until their extended branches are activated by electrical signals from neurons or the presence of harmful substances.⁴ Activated microglia can secrete a variety of anti-inflammatory chemicals to prevent neurological problems, such as brains tumors and axonal injury.⁵ Microglia can also increase the permeability of the blood-brain barrier, allowing bodily immune cells to assist with brain immune defense.² A negative feedback mechanism in microglia regulates their own immune response as well as that of other helper immune cells.

In most pathologies, microglia experience a change in their normal activity caused by environmental factors.² Gliomas, or tumors in the neural glial tissues, are diseases that microglia should be able to handle. However, cells from the two microglial subcategories that migrate toward gliomal cells, M1 and M2, react differently in the gliomal microenvironment. M1 microglia promote tumor degradation by activating other immune cells and phagocytizing gliomal tumor cells. However, M2 microglia promote tumor growth by inhibiting proinflammatory cytokine activity and slowing immune cell responses.⁶ Cytokines are small proteins that aid cell communication and regulate cellular immune response.⁷ Additionally, tumor necrosis factor (TNF) stimulates inactivated microglial migration into the glioma, carving a pathway for glioma to migrate to other areas of the brain. Some gliomal therapies have focused on inhibiting the activity of M2 microglia. Various drug treatments that inhibit M2 activity have been shown to decrease gliomal proliferation in vivo. However, the success of these therapies should be treated with caution: gliomal immunosuppression both inactivates multiple immune responses outside of microglia and has the plasticity to circumvent anti-tumor therapies.⁶

Reduced microglial activity is related to a variety of neurodevelopmental disorders such as autism that demonstrate decreased connectivity in the brain.⁸ Microglia are responsible for forming mature spines and eliminating immature connections in the brain during post-natal development. This seems counterintuitive; how can decreasing in microglial activity, which causes less synaptic pruning, somehow cause less connectivity in the brain? Reduced microglial activity is actually preventing the brain from eliminating immature spine connections, which leads to fewer mature connections. Failing to eliminate immature connections physically hinders other synapses from forming multiple connections. Techniques that would increase microglial activity include increasing CR3/C3 pathway activity, which triggers synaptic pruning via an unknown mechanism.⁹ Although microglial therapies might not entirely eliminate autism, which acts through a variety of known and unknown neurological mechanisms, there is potential for ameliorating some symptoms.

Microglia often experience increased sensitivity in the aging brain caused by an increased expression of activation markers.¹⁰ This leads to several inflammatory neurological illnesses, including Alzheimer’s disease (AD). Microglia are once again found to play contradicting roles in the progression of Alzheimer’s; their activity is critical in producing neuroprotective anti-inflammatory cytokines, removing cell debris, and degrading amyloid-β protein, the main component of amyloid plaques that cause neurofibrillary tangles.¹⁰ Alternatively, activating microglia runs the risk of hyper-reactivity, which can cause extreme detriment to the central nervous system. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to decrease the amount of activated microglia by 33% in non-AD patients. Treatment on microglial cultures increased amyloid-β phagocytosis and decreased inflammatory cytokine secretion. However, this treatment did not alter the microglial inflammatory activity in AD patients. The ideal microglial therapy for neuroinflammatory illnesses would result in the expression of only positive microglial activity, such as amyloid-β degradation, and the elimination of negative activity, such as pro-inflammatory secretion. One mechanism that increases pro-inflammatory secretion is amyloid-β binding to formyl peptide receptor (FPR) on microglia. Protein Annexin A1 (ANXA1) binding to FPR has been seen to inhibit interactions between amyloid-β and FPR, which decreases pro-inflammatory secretion.

Central nervous system pathology researchers often speculate as to how certain bacteria and viruses are able to enter the brain and consider mechanisms such as increase in blood-brain barrier permeability and chemical exchange through cerebrospinal fluid. However, the discovery of nervous system lymphatic vessels may put much of this speculation to rest and open up an entirely new venue of neuroimmunological research.¹¹ The interaction between microglial immune function and these lymphatic vessels could introduce treatments that recruit microglia to sites where bacterial and viral infections are introduced into the brain. Alternatively, therapies that increase bodily immune cell and microglial interactions by increasing the presence of bodily immune cells in the brain could boost the neural immune defense. Other approaches could involve introducing drugs that increase or decrease microglial-activity into more accessible lymphatic vessels elsewhere in the body for proactive treatment of neonatal brain diseases. Although we have made some steps towards curing brain diseases that involve microglial activity, coordinating these treatments with others that increase neural immune defenses has the potential to create effective treatment for those afflicted by devastating and currently incurable neurological diseases.

References

1. Hughes, V. Nature 2012, 485, 570-572.
2. Yang, I.; Han, S.; Kaur, G.; Crane, C.; Parsa, A. Journal of Clinical Neuroscience 2010, 17, 6-10.
3. Ferrer, I.; Bernet, E.; Soriano, E.; Del Rio, T.; Fonseca, M. Neuroscience 1990, 39, 451-458.
4. Christensen, R.; Ha, B.; Sun, F.; Bresnahan, J.; Beattie, M. J. Neurosci. Res. 2006, 84, 170-181.
5. Babcock, A.; Kuziel, W.; Rivest, S.; Owens, T. Journal of Clinical Neuroscience 2003, 23, 7922-7930.
6. Wei, J.; Gabrusiewicz, K.; Heimberger, A. Clinical and Developmental Immunology 2013, 2013, 1-12.
7. Zhang, J.; An, J. International Anesthesiology Clinics 2007, 45, 27-37.
8. Zhan, Y.; Paolicelli, R.; Sforazzini, F.; Weinhard, L.; Bolasco, G.; Pagani, F.; Vyssotski, A.; Bifone, A.; Gozzi, A.; Ragozzino, D.; Gross, C. Nature Neuroscience 2014, 17, 400-406.
9. Schafer, D.; Lehrman, E.; Kautzman, A.; Koyama, R.; Mardinly, A.; Yamasaki, R.; Ransohoff, R.; Greenberg, M.; Barres, B.; Stevens, B. Neuron 2012, 74, 691-705.
10. Solito, E.; Sastre, M. Frontiers in Pharmacology 2012, 3.
11. Louveau, A.; Smirnov, I.; Keyes, T.; Eccles, J.; Rouhani, S.; Peske, J.; Derecki, N.; Castle, D.; Mandell, J.; Lee, K.; Harris, T.; Kipnis, J. Nature 2015, 523, 337-341.

How Bionic Eyes Are Changing the Way We See the World

Catalyst Volume 9

Most blind people wear sunglasses, but what if their glasses could actually restore their vision? Such a feat seems miraculous, but the development of new bionic prostheses may make such miracles a reality. These devices work in two ways: by replacing non-functional parts of the visual pathway or by creating alternative neural avenues to provide vision.

When attempting to repair or restore lost vision, it is important to understand how we normally receive and process visual information. Light enters the eye and is refracted by the cornea to the lens, which focuses the light onto the retina. The cells of the retina, namely photoreceptors, convert the light into electrical impulses, which are transmitted to the primary visual cortex by the optic nerve. In short, this process serves to translate light energy into electrical energy that our brain can interpret. For patients suffering from impaired or lost vision, one of the steps in this process is either malfunctioning or not functioning at all.^1,2

Many patients with non-functional vision can be treated with current surgical techniques. For example, many elderly individuals develop cataracts, in which the lens of the eye becomes increasingly opaque, resulting in blurred vision. This condition can be rectified fairly simply with a surgical replacement of the lens. However, loss of vision resulting from a problem with the retina or optic nerve can very rarely be corrected surgically due to the sensitive nature of these tissues. Such pathologies include retinitis pigmentosa, an inherited degenerative disease affecting retinal photoreceptors, and head trauma, which can damage the optic nerve. In these cases, a visual prosthesis may be the solution. These devices, often called “bionic eyes,” are designed to repair or replace damaged ocular functions. Such prostheses restore vision by targeting damaged components in the retina, optic nerve, or the brain itself.

One set of visual prostheses works by correcting impaired retinal function via electrode arrays implanted between the retinal layers. The electrodes serve as substitutes for lost or damaged photoreceptors, translating light energy to electrical impulses. The Boston Retinal Implant Project has developed a device involving an eyeglass-mounted camera and an antenna implanted in the skin near the eye.³ The camera transmits visual data to the antenna in a manner reminiscent of a radio broadcast. Then, the antenna decodes the signal and then sends it through a wire to an implanted subretinal electrode array, which relays it to the brain. The problem with this system is that the camera is fully external and unrelated to the eye’s position, meaning the patient must move his or her entire head to survey a scene. Germany’s Retinal Implant AG team seeks to rectify this problem with the Alpha IMS implant system. In this system, the camera itself is subretinal, and “converts light in each pixel into electrical currents.”²

The Alpha IMS system is still undergoing experimental clinical trials in Europe, but it is facing some complications. Firstly, the visual clarity of tested patients is around 20/1000, which is well below the standard for legal blindness. Secondly, the system’s power supply is implanted in a very high-risk surgical procedure, which can endanger patients. In an attempt to overcome the problems faced by both The Boston Retinal Implant Project and Retinal Implant AG, Dr. Daniel Palanker at Stanford and his colleagues are currently developing a subretinal prosthesis involving a goggle-mounted video camera and an implanted photodiode array. The camera receives incoming light and projects the image onto the photodiode array, which then converts the light into pulsed electrical currents. These currents stimulate nearby neurons to relay the signal to the brain. As Dr. Palanker says, “This method for delivering information is completely wireless, and it preserves the natural link between ocular movement and image perception.”² Human clinical trials are slated to begin in 2016, but Palanker and his team are confident that the device will be able to produce 20/250 visual acuity or better in affected patients.

A potentially safer set of visual prostheses includes suprachoroidal implants. Very similar to the aforementioned subretinal implants, these devices also replace damaged components of the retina. The only difference is that suprachoroidal implants are placed between the choroid layer and the sclera, rather than between the retinal layers. This difference in location allows these devices to be surgically implanted with less risk, as they do not breach the retina itself. Furthermore, these devices are larger compared to subretinal implants, “allowing them to cover a wider visual field, ideal for navigation purposes.” Development of suprachoroidal devices began in the 1990s at both Osaka University in Japan and Seoul National University in South Korea. Dr. Lauren Ayton and Dr. David Nayagam of the Bionic Vision Australia (BVA) research partnership are heading more current research. BVA has tested a prototype of a suprachoroidal device in patients with retinitis pigmentosa, and results have been promising. Patients were able to “better localize light, recognize basic shapes, orient in a room, and walk through mobility mazes with reduced collisions.” More testing is planned for the future, along with improvements to the device’s design.²

Both subretinal and suprachoroidal implants work by replacing damaged photoreceptors, but they rely on a functional neural network between the retina and the optic nerve. Replacing damaged photoreceptors will not help a patient if he or she lacks the neural network that can transmit the signal to the brain. This neural network is composed of ganglion cells at the back of the retina that connect to the optic nerve; these ganglion cells can be viewed as the “output neurons of the eye.” A third type of visual prosthesis targets these ganglion cells. So-called epiretinal implants are placed in the final cell layer of the retina, with electrodes directly stimulating the optic nerve. Because these devices are implanted in the last retinal layer, they work “regardless of the state of the upstream neurons”.² So the main advantage of an epiretinal implant is that, in cases of widespread retinal damage due to severe retinitis pigmentosa, the device provides a shortcut directly to the optic nerve.

The most promising example of an epiretinal device is the Argus II Visual Prosthesis System, developed by Second Sight. The device, composed of a glasses-mounted camera that wirelessly transmits visual data to an implanted microelectrode array, received FDA marketing approval in 2012. Clinical trials have shown a substantial increase in visual perception and acuity in patients with severe retinitis pigmentosa, and the system has been implanted in more than 50 patients to date.

The common limitation of all these visual prostheses (subretinal, suprachoroidal, and epiretinal) is that they rely on an intact and functional optic nerve. But some blind patients have damaged optic nerves due to head trauma. The optic nerve connects the eye to the brain, so for patients with damage in this region, bionics researchers must find a way to target the brain itself. Experiments in the early 20th century showed that, by stimulating certain parts of the brain, blind patients could perceive light flashes known as phosphenes. Building from these experiments, modern scientists are working to develop cortical prostheses implanted in either the visual cortex of the cerebrum or the lateral geniculate nucleus (LGN), both of which are key in the brain’s ability to interpret visual information. Such a device would not truly restore natural vision, but produce artificial vision through the elicitation of phosphene patterns.

One group working to develop a cortical implant is the Monash Vision Group (MVG) in Melbourne, Australia, coordinated by Dr. Collette Mann and co. MVG’s Gennaris bionic-vision system consists of a glasses-mounted camera, a small computerized vision processor, and a series of multi-electrode tiles implanted in the visual cortex. The camera transmits images to the vision processor, which converts the picture into a waveform pattern and wirelessly transmits it to the multi-electrode tiles. Each electrode on each tile can generate a phosphene; all the electrodes working in unison can generate phosphene patterns. As Dr. Mann says, “The patterns of phosphenes will create 2-D outlines of relevant shapes in the central visual field.”² The Illinois Institute of Technology is developing a similar device called an intracortical visual prosthesis, termed the IIT ICVP. The device’s developers seek to address the substantial number of blind patients in underdeveloped countries by making the device more affordable. The institute says that “one potential advantage of the IIT ICVP system is its modularity,” and that by using fewer parts, they “could make the ICVP economically viable, worldwide.”⁴

These visual prostheses represent the culmination of decades of work by hundreds of researchers across the globe. They portray a remarkable level of collaboration between scientists, engineers, clinicians, and more, all for the purpose of restoring vision to those who live without it. And with an estimated 40 million individuals worldwide suffering from some form of blindness, these devices are making miracles reality.

References

1. The Scientist Staff. The Eye. The Scientist, 2014, 28.
2. Various Researchers. The Bionic Eye. The Scientist, 2014, 28.
3. Boston Retinal Implant Project. http://biomed.brown.edu/Courses/BI108/2006-108websites/group03retinalimplants/mit.htm (accessed Oct. 9, 2015)
4. Intracortical Visual Prosthesis. http://neural.iit.edu/research/icvp/ (accessed Oct. 10, 2015)

From a Pile of Rice to an Avalanche: A Brief Introduction to Granular Materials

Catalyst Volume 9

Communities living at the foot of the Alps need a way to predict the occurrence of avalanches for timely evacuation, but monitoring the entire Alpine range is impossible. Fortunately for those near the Alps, the study of granular materials has allowed scientists to move mountains into labs and use small, contained systems (like piles of rice) to simulate real-world avalanche conditions. Granular materials, by definition, are conglomerates of discrete visible particles that lose kinetic energy during internal collisions; they are neither too small to be invisible to the naked eye, nor too big to be studied as distinct objects.¹ The size of granular material situates them between common objects and individual molecules.

While studying extremely small particles, scientists stumbled upon an unsettling contradiction: the classical laws governing the macroscopic universe do not always apply at microscopic scales. For example, Niels Bohr sought to apply classical mechanics to explain the orbits of electrons around nuclei by comparing them to the rotation of planets around stars. However, it was later discovered that an electron behaves in a much more complicated way than Bohr had anticipated. At its size, the electron gained properties that could only be described through an entirely new set of laws known as quantum mechanics.

Though granular materials do not exist at the quantum level, their distinct size necessitates an analogous departure from classical thought. A new category of physical laws must be created to describe the basic interactions among particles of this unique size. Intuitively, this makes sense; anyone who has cooked rice or played with sand knows that the individual grains behave more like water than solid objects. Scientists are intrigued by these materials because of the variation in their behaviors in different states of aggregation. More importantly, since our world consists of granular materials such as coffee, beans, dirt, snowflakes, and coal, their study sheds new light on the prediction of avalanches and earthquakes.

The physical properties of granular flow vary with the concentration of grains. At different concentrations, the grains experience different magnitudes of stress and dissipate energy in different ways. Since it is hard to derive a unifying formula to describe granular flows of varying concentrations, physicists use three sets of equations to fit their states of aggregation, resembling the gaseous, liquid, and solid phases. When the material is dilute enough for each grain to randomly fluctuate and translate, it acts like a gas. When the concentration increases, particles collide more frequently and the material functions as a liquid. Since these particles do not collide elastically, a fraction of their kinetic energy dissipates into heat during each collision. The increased frequency of inelastic collisions between grains in the analogous liquid phase results in increasing energy, dissipation, and greater stress. Finally, when the concentration increases to 50% or more, the material resembles a solid. The grains experience significant contact, resulting in predominantly frictional stress and energy dissipation.¹

Avalanches come in two types, flow and powder, each of which requires a specific combination of the gas, liquid, and solid granular models. In a flow avalanche, the descending layer consists of densely packed ice grains. The solid phase of granular materials best models this, meaning that friction becomes the chief analytical aspect. In a powder avalanche, particles of snow do not stick together and descend in a huge, white cloud.² The fluid and solid models of granular materials are equally appropriate here.

Physicists can use these avalanche models to investigate the phenomena leading up to a real-world avalanche. They can simulate the disturbance of a static pile of snow by constantly adding grains to a pile, or by perturbing a layer of grains on the pile’s surface. In an experiment conducted by statistical physicists Dr. Daerr and Dr. Douady, layers of glass beads of 1.8 to 3mm in diameter were poured onto a velvet surface, launching two distinct types of avalanches under different regimes decided by the tilt angle of the plane and the thickness of the layer of glass beads.³

For those of us who are not experts in avalanches, there are a few key points to take away from Daerr and Douady. They found that a critical tilt angle exists for spontaneous avalanches. When the angle of the slope remained under the critical angle, the size of the flow did not grow, even if a perturbation caused an additional downfall of grains. Interestingly, when the angle of the slope was altered significantly, the snow uphill from the perturbation point also contributed to the avalanche. That means that avalanches can affect higher elevations than their starting points. Moreover, the study found that the angle of the remaining slope after the avalanche was always less than the original angle of the slope, indicating that after a huge avalanche, mountains would remain stable until a change in external condition occured.³ A. Often, a snow mountain with slopes exceeding the critical angle can remain static and harmless for days, because of the cohesion between particles.

Situations become complicated if the grains are not completely dry, which is what happens in real snow avalanches. In these scenarios, physicists must modify existing formulas and conduct validating experiments to predict the behaviors of these systems. Granular materials are not limited to predicting avalanches. In geophysics, scientists have investigated the relation of granular materials to earthquakes. For instance, one study used sound waves and glass beads to study the effects of earthquake aftershocks.⁴ Apart from traditional modeling with piles of rice or sand, the understanding of granular materials under different phases paves the way for computational modeling of large-scale natural disasters like avalanches and earthquakes. These studies will not only help us understand granular materials themselves, but also help us predict certain types of natural disasters.

References

1. Jaeger, H. M., Nagel, S. R., and Behringer, R. P. Granular Solids, Liquids and Gases. Rev. Mod. Phys., 1996, 68, No.4, 1259-1273.
2. Frankenfield, J. Types of Spring and Summer Avalanches. http://www.mountain-guiding.com/avalanche/info/spring-types.html (accessed Oct. 29, 2015).
3. Daerr, A. and Douady, S. Two Types of Avalanche Behaviour in Granular Media. Nature, 1999, 399, 241-243.
4. Johnson P. A., et al. Effects of acoustic waves on stick–slip in granular media and implications for earthquakes. Nature, 2008, 451, 57-60.

Not Many Other Fish in the Sea: Our Current Overfishing Crises

Catalyst Volume 9

Prevailing notions of the ocean make it seem as if it is "too big to fail” since it takes up 70% of the surface of Earth and contains 321,003,271 cubic miles of water.¹ Additionally, most of the oceans’ immense biodiversity has yet to be documented. The Census of Marine Life estimates that there could be between 178,000 to 10,000,000 different species living in ocean shoreline habitats due to the vast abundance of photosynthesizing microbes.² However, like any ecosystem, the oceans are not immune to anthropogenic and environmental stressors such as overfishing, climate change, and pollution. There are many interconnected problems surrounding the way in which people currently treat the oceans. Extracting large amounts of fish for human consumption threatens the dynamic balance that currently exists and threatens scientists’ potential for making groundbreaking discoveries about what lies below.

In 2010, the United Nations predicted that over 80% of the world’s fish are reported as fully exploited or overexploited, and thus “require effective and precautionary management.”³ Overexploitation refers to the extraction of marine populations to unsustainable levels.4 Fishing techniques have become exponentially more efficient since the Industrial Revolution, focusing on getting the largest catches in the fewest trips. Today’s fishing fleets are so large that it would require two to three times Earth’s supply of fish to fill them.⁴ These harmful practices lead to three main types of overfishing:

1. Growth overfishing: The removal of larger fish leaves behind only individuals that are too small to maximize the yield, or full amount of fish that could theoretically be obtained.⁵
2. Recruitment overfishing: When adult fish are excessively taken out of the ecosystem, recruitment and stock productivity decreases.⁵
3. Ecosystem overfishing: The targeting of a particular species leads to serious trophic cascades and ecological consequences.⁵

Unfortunately, the most popularly consumed fish species are subject to all three practices. Bluefin tuna, sturgeon, sea bass, and Atlantic salmon are examples of large, long-lived predatory species that only provide a few offspring each breeding cycle.⁵ For example, Bluefin tuna release ten million eggs each year, but only a small number survive to adulthood. Even then, these tuna do not reach reproductive maturity until eight to twelve years of age.⁶ When the largest fish are specifically targeted, many ecological consequences arise. Removing the largest fish of the largest species in an ecosystem significantly decreases the mean size for that species. As a result, only smaller fish are left to reproduce.⁷ This shift causes trophic level decline: as species at higher trophic levels are overfished, fishermen decide to catch the comparatively larger fish at lower trophic levels.⁷ This vicious cycle continues so that the average size of fish consumed decreases significantly. This phenomenon, known as “eating down the food chain,” puts many fish at risk, including herbivorous fish in coral reef ecosystems.⁷ To maintain a coral-dominated state, herbivorous fish consume macro-algae that otherwise would overgrow and suffocate corals. When coral-dominated reefs become overtaken by macro-algae, habitats for many other fish and organisms are severely reduced. Over 25% of the world’s fish species live exclusively within these three-dimensional coral communities, which themselves only take up 0.1% of the ocean floor.⁵ Not only are species being depleted at the very top of the food chain, smaller species that are endemic to specific ocean environments are also indirectly experiencing survival pressure.

These problems are further magnified by the fact that current fishing practices produce a large amount of by-catch, or the incidental capture of non-target species.⁵ The rustic image of a humble fisherman using a single hook at the end of a line no longer reflects reality for most commercial fishermen. Now, longlines are weighted at the bottom and can have as many as 3,000 hooks attached, probing deeper into the water column.⁸ A similar weighted system exists for large fishing nets, known as trawl nets, so that shellfish and other small or bottom-dwelling organisms can be collected in larger quantities. Bottom trawling, the practice of dragging a trawl net across the ocean floor, has contributed to 95% of the damage inflicted on deep water systems by destroying and smothering benthic communities.⁹ These practices are non-specific in nature, and thus collect anything and everything that attaches or gets caught. Fishing gear alone has threatened around 20% of shark species with extinction and leads to over 200,000 loggerhead sea turtles deaths annually.¹⁰ Sylvia Earle, a renowned ocean-conservationist, describes these unsustainable fishing practices as “using bulldozers to kill songbirds.”¹¹

The United Nations now predicts that by 2050, the world will run out of commercially viable catches and oceans could turn fishless.³ Driving this problem is the fact that seafood consumption has increased over the past 30 years.¹² Many coastal communities and developing countries rely on fishing as their main source of income and protein, with approximately 2.9 million people relying on fish for over 20% of their animal protein intake. One of the largest importers, the United States, imports 91% (by value) from other countries with lower production costs.¹³ The cheap labor comes from subsistence fishermen, who meet this increased demand by opting for unsustainable practices. Consequently, a “poverty cycle” emerges, where short-term survival takes precedence over sustainability and conservation efforts, further exacerbating ecological and economic damages.¹⁴

Recognizing that environmental considerations alone could put many developing countries at risk, policymakers have adopted a community-based approach in the planning, construction, implementation, and management of preservation policies.¹⁵ This ecosystem approach to fisheries, strives to ensure that the capability of aquatic ecosystems to provide the necessary resources for human life is maintained for present and future generations.¹⁶

The establishment of Marine Protected Areas, or MPAs, is another effective technique similar to the National Park Service’s preservation programs. Although MPAs have a wide range of management plans and enforcement, all strive to limit or restrict human activity so that natural populations can be restored.⁵ Allowing an environment to restore its fish populations without any human mitigation can take a long time, and the most effective MPAs extend across large tracts of area that can more fully encompass fish populations and migratory species.⁵ Because these areas often overlap with highly profitable fishing zones, MPAs are regularly met with backlash from coastal communities and later can be hard to enforce.¹⁷

These international efforts to reduce the amount of seafood extracted from ocean environments are generally invisible in a grocery store, so it is easy for consumers to engage passively with the food they see. However, recognizing the production, labor, and ecosystem that goes into fish and fish products (and all foods) is critical for maintaining the livelihood of the world’s natural environments. The ocean may seem vast, but there is not an infinite supply of resources that can meet current demands.

References

1. National Oceanic and Atmospheric Administration. http://oceanservice.noaa.gov/facts/oceanwater.html (accessed Oct. 31, 2015).
2. Smithsonian Institute. http://ocean.si.edu/census-marine-life (accessed Nov. 1, 2015).
3. Resumed Review Conference on the Agreement Relating to the Conservation and Management of Straddling Fish Stocks and Highly Migratory Fish Stocks; United Nations: New York, 2010.
4. Marine Biodiversity and Ecosystem Functioning. http://www.marbef.org/wiki/over_exploitation (accessed Oct. 31, 2015).
5. Sheppard, C.; David,S.; Pilling, G. The Biology of Coral Reefs,1; Oxford University Press: 2009.
6. World Wildlife Foundation http://wwf.panda.org/what_we_do/endangered_species/tuna/atlantic_bluefin_tuna/ (accessed Nov. 1, 2015).
7. Pauly, D., et al. Science. 1998, 279, 860-863.
8. Food and Agriculture Organization. http://www.fao.org/fishery/fishtech/1010/en (accessed Feb. 25, 2016).
9. The Impacts of Fishing on Vulnerable Marine Ecosystems; General Assembly of the United Nations: Oceans and the Law of the Sea Division, 2006.
10. Monterey Bay Aquarium. http://www.seafoodwatch.org/ocean-issues/wild-seafood/bycatch. (accessed Oct. 31, 2015).
11. Saeks, Diane Dorrans. US oceanographer Dr. Sylvia Earle. Financial Times, Aug. 9, 2013.
12. The State of World Fisheries and Aquaculture; Food and Agriculture Organization; United Nations: Rome 2014.
13. Gross, T. ‘The Great Fish Swap’: How America Is Downgrading Its Seafood Supply. National Public Radio, Jul. 1, 2014.
14. Cinner, J. et al. Current Biology. 2009. 19.3, 206-212.
15. Agardy, T. M. ; Information Needs for Marine Protected Areas: Scientific and Societal; 66.3; Bulletin of Marine Science, 2000; 875-878.
16. Food and Agriculture Organization. http://www.fao.org/fishery/topic/13261/en (accessed Nov. 1, 2015).
17. Agardy, T.M.; Advances in Marine Conservation: The Role of Marine Protected Areas; 9.7; Trends in Ecology and Evolution, 1994; 267-270.