The Pitt Pulse - Volume IV Issue II

VOLUME IV ISSUE II || DECEMBER 2013

VOLUME IV ISSUE II || DECEMBER 2013

4

Computational Super Science

18

Jessica Collins

6

Vighnesh Viswanathan

Evolution of Cancer Research

19

Rashmi Kumar

9

Pregnant With Debt: How Midwives Deliver Solutions to U.S. Health Care Costs

21

The Evolution of Lactase Persistance

Research for a Reason: A Fellowship that Keeps its Eye on Treatment Tadhg Schempf

Abigail Wang

12

Breaking the Barrier: A Commentary on David Biro’s Listening to Pain Rashmi Kumar

Vivian Liang

10

The History of Antiseptic Medicine

22

Did That Actually Happen? Shedding Light on False Memories

Appocalypse Now: The Affordable Care Act and You Jason Naughton

Manisha Kintali

15

The God Particle

16

The One: A Millenial Search for a Partner

Jad Hilal

A human colon cancer cell Read about Evolution of Cancer Research Pg 6

Maria Marcos

2

THEPITTPULSE.COM

A Letter From the Editor:

The phenomenal response The Pitt Pulse received after the release of our first issue has encouraged our team to push the boundaries of design and content here in our second publication of the academic year. We strive to bring you information that uncovers the relevance of fields such as history, computer science, physics, and politics within the medical community. The clear and honest communication of information between spheres of study is becoming evermore important as we continue to discover more about our world, and ourselves. Furthermore, we should take care not to dive headfirst into the future without paying homage to the past; examination and appreciation of our previous accomplishments, and controversies, is the ultimate tool for learning how to advance productively forward.

The goal of this publication is to bridge paradigms, to applaud inquisitive individuals of all backgrounds, and to provide motivation for finding and strengthening the shared pathways between our worlds. Reinforcement of interdisciplinary communication and the relationships this communication inspires will lead us to more a powerful and universal understanding of our research and discoveries. This panoptic understanding generates not only a broader range of impact for our developments, but a unity that will encourage insightful cooperation for future projects.

We hope to inspire you to look beyond the boundaries of your interests‌ Beverly Hersh Editor in Chief

EDITOR IN CHIEF

PUBLISHER

EDITORIAL TEAM

WEB DESIGN TEAM

BEVERLY HERSH

NIAZ KHAN

LINDSAY ALLEN IMAZ ATHAR MELISSA CARLSON JESSICA CRAIG NATALIE ERNECOFF ELIZABETH FUGA SARAH WENRICH

JASON NAUGHTON* JASON TAYLOR

DISTRIBUTION TEAM IMAZ ATHAR * RACHEL KOSCIUSKO HAADI ALI LAUREN MCNEIL RUHEE JAIN

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LINDSAY ALLEN

PUBLIC RELATIONS TEAM ELIZABETH FUGA*

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THEPITTPULSE.COM

3

beh56:~ jmc219$ ssh jmc219@unixs.cis.pitt.edu password: ********* Checking sshd-kbdint system rights for <jmc219> Last Login: Wed Nov 20 12:17:17 2013 from beh56.labs.pitt University of Pittsburgh

UNIX Services (1) unixsl $ nano computational_super_science.txt

/****************************************************** Computational_Super_Science

*******************************************************

created by Jessica Collins *****************************************************************************/ //execute this code for the article public class article(){

article(1) = [”When you think of a chemistry or biology lab, you likely imagine a group of scientists performing experiments that involve microscopes and test tubes, putting in a lifetime of work to uncover small details of the natural world. While this is the case in most labs, there are many nowadays which are not only more technologically advanced, but also involve no lab-bench experiments at all. Bioinformatics, or “dry lab biology” as it has been nicknamed, is an emerging field which involves no hands on experimenting, just a high degree of computer science knowledge. The scientists, who are frequently people with backgrounds in information technology, write statistical algorithms to both simulate complex systems in biology and to analyze the high amount of data that has already been published. This new discovery method has produced a vast number of advances in medicine using databases of available information.”];

article(2) = [”The Pittsburgh Supercomputing Center (PSC), a group at the University of Pittsburgh and Carnegie Mellon University, received a 7.6 million dollar grant from the National Science Foundation in October of this year to fund a project called the Data Exacell. The goal of the Data Exacell is to create a prototype of next generation technology which closely couples analytical resources with storage technology. This is a project building upon the Data Supercell, a data storage system with the world’s largest shared memory that was developed two years ago. Right now, one of the major issues in bioinformatics is the retrieval and usage of specific information from large computer databases. With all of the information the computer has access to, it is difficult for scientists to pick out the specific pieces they want to use for their research. “High-performance computing used to be all about solving partial differential equations, now it’s much more about how you move information around,” said Nick Nystrom, PSC’s Director of Strategic Applications. The Data Exacell project will be tested using selected data-intensive research projects in diverse fields of science such as biology, astronomy and computer science.“];

var pageNumber = 4;

article(3) = [“The PSC is involved in a wide range of projects. One in particular, Blacklight, involves next-generation gene sequencing to examine the genomes of various organisms at high speeds. This computer system operates at much faster rates than traditional DNA sequencers by doing short sequence reads at a time. Another PSC project is involved with connectomics, a field of neuroscience which uses electron microscopy to image sections of the brain which are then re-assembled in a computer database into a three-dimensional image.

This year the Nobel Prize in Chemistry was given to three scientists, Martin Karplus, Michael Levitt, and Arieh Warshel, for developing computer models for uncovering chemical processes by combining classic and quantum physics. The three Nobel Prize winners utilized the PSC systems to collaborate on their research. ”];

article(4) = [”With decades worth of published information, collaboration among research groups across the globe is more important for advancing the fields of science and medicine than ever before. While complex data storage systems already exist, using that information in an effective manner is an issue that is only now being addressed. The PSC plays a key role in developing technology that allows for such collaboration. “We are sort of a service organization for the community, providing scientists with infrastructure and the tools they need to do their work, whatever those may be,” said Markus Dittrich, Ph.D., head of the PSC’s National Resource for Biomedical Supercomputing.”];

article(5) = [”For the scientific community, this type of technology means a more efficient method for both conducting and analyzing research.

For the general public, this could lead to better drug treatment options, the possibility of gene sequencing, and doctors with a broader spectrum of readily accessible information. Students interested in the fields of biology and chemistry will likely need to develop a background in computer science to make an impact in research fields in the future. “I think what’s important for students to realize right now is that a lot of boundaries between the fields have broken down and you shouldn’t just think of yourself as a biologist. It’s good to acquire skills outside of that range,” said Dittrich.”];

article(6) = [” The PSC is currently working with Pitt’s World History department to create a web-based interface that will allow them to conduct data searches in real-time. This application can extend across multiple fields of academia. With these developments in technology, there is huge potential for the future in science in going beyond the limits of “wet lab” experimentation.”]; } System.out.Println(article()); **Class compiled - no syntax errors.** ************************************************************************** (2) unixsl $ mv computational_super_science.txt ~home/m/a/mam503/public (3) unixsl $ pwd afs/pitt.edu/home/j/m/jmc219 (4) unixsl $ exit (5) unixsl $

var pageNumber = 5;

EVOLUTION

OF

CANCER RESEARCH

Rashmi Kumar

Olivera J. Finn, Ph.D. University of Pittsburgh Department of Immunology

1913

Founding of the American Cancer Society

130-200 AD

Galen: Extracting Humors, draining blood, excising small visible tumors

Mustine (1919) 6

T

his year marks the 100th anniversary of the American Cancer Society. With a century of recognized fight against cancer, it is only fitting that we reminisce about the strides humanity has made against a disease that has posed as both a catalyst and conundrum in medicine.

From brute force chemotherapy to the period of cell signaling to the dawn of immunotherapy, oncology (the study of cancer) can be traced through various eras. The scientific perspective on cancer has morphed throughout the years and the evolution of cancer therapy has been remarkable.

In the Ancient World, Celsus and Galen— two famous medical authorities—labeled cancer as an incurable disease. Before the invention of microscopy, the origin of cancer and its pathology was shrouded in mystery. The first phase of cancer therapy was characterized by “brute force” treatments based on basic physical observations and experiments. “Humors” were extracted and blood was leeched to quench the cancer, and tumors were excised by surgical techniques. Surprisingly, this philosophy of utilizing physical observations to propel cancer therapy serendipitously led to the discovery of the first chemotherapeutic drug: mustine. Also known as nitrogen mustard, mustine is a chemical warfare agent used extensively during the World War I era. In 1917, Edward Krumbhaar, M.D., from the University of Pennsylvania, was sent to France as a medical officer in the American Expeditionary Forces. He conducted autopsies of soldiers exposed to mustard gas and was the first to publish the remarkable leukopenic effects of nitrogen mustard on victims in his book Blood and Bone Marrow in Mustard Gas Poisoning in 1919.

Soldiers exposed to this chemical had severely reduced numbers of circulating white blood cells.

In 1941, pharmacologists Alfred Gilman, M.D., Ph.D., and Louis Goodman, M.D., were determining the toxicity levels of mustard gas in white rabbits.

They, like Krumbhaar, saw highly reduced numbers

of white blood cells. If such an agent could be used to reduce the numbers of cancerous white blood cells, the patient had a chance at survival. In their quest to find an antidote for mustard gas poisoning, they had inadvertently stumbled upon the anticancer therapeutic potential of nitrogen mustard.

The discovery of mustine was the gateway to a new era of cancer therapy.

Until chemotherapy, surgical and radiation techniques could only target solid mass tumors.

Additionally, patients had a high chance of survival only if the tumors were small enough to be isolated and removed completely. The scientific approach to cancer therapy changed course; the new focus was on the discovery of new chemical compounds that could target actively dividing cells.

Chemotherapy was valuable in that it could be used in combination with surgery and radiation with great efficiency, thereby decreasing the chances of tumor regrowth. With chemotherapy, cancers that metastasized (traveled to different organs) and blood cancers such as leukemia or lymphoma could be cured. Unfortunately, chemotherapy affected noncancerous cells as well, promptting the need to create drugs that could specifically target numerous cancer

2010 1965

Cisplatin

Publishing of Emperor of all Maladies: Biography of Cancer

1919

Edward Krumbhaar first reports leukopenic effects of Nitrogen Mustard

2001

Imatinib

2013

1 millionth bone marrow transplant

2012

Start of colon cancer vaccine clinical trials 7

cell populations. In short, oncologists were hoping to find out what characteristics of cancer cells could be exploited for treatment. One miracle drug that arrived during this era of cancer research was Imatinib (or Gleevec). The discovery of Imatinib allows us to take a look into the minds of physicians and researchers during this exciting time.

Officially approved by the FDA in 2001, Imatinib was discovered by Brian Druker, M.D., at the Oregon Health and Science University. Imatinib worked because of one simple idea. It proposed a lock and key model of drug therapy. Imatinib is an inhibitor of a receptor that is over expressed in cancer cells and prevents constant activation of the receptor by binding to it. It effectively reduces the uncontrolled growth of cancer cells. Imatinib was one of the first drugs that took a characteristic unique to cancer cells and applied it to drug innovation.

While cancer therapy has evolved continuously over the past century, the last decade in oncology has been one of the most innovative. Society is now at the cusp of a new era of cancer therapy that revolves around cancer vaccines. The current phase of cancer therapy taps into the potential of the human immune system and hopes to use our body’s defense mechanisms to identify cancer cells that have previously gone undetected. Interestingly, our very own University has been at the forefront of propelling research focused on cancer vaccines. The research of Pitt Immunologist Olivera Finn, Ph.D., on the colon cancer vaccine holds special relevance in this path-breaking topic.

Finn, a recipient of the American Cancer Society Faculty Award, shared her thoughts on the evolution of cancer research through the decades. For her, the modern shift in understanding cancer came from realizing its impact on the immune system. “You cannot treat cancer as though it is in a petri dish,” says Dr. Finn. “You must think of the host, you must think of the indelible changes that occur in the immune system as a result of this disease.” It is this type of novel thinking that enables her research to introduce a level

8

of specificity to cancer therapy never seen before. Her vaccine is constructed around a protein synthesized by the colon cancer cells. The idea is that if the immune system could be trained to mount a response against this protein then, in principle, they would also attack the cancer cells that secrete this protein. Finn’s vaccine is currently in small Phase I and II clinical trials and shows promise.

Out of the initial 39 people that were administered this vaccine, 17 showed a strong immune response with specificity for the protein. The beauty of our adaptive immune system and cancer vaccines is that they can be highly specific. This approach is different from chemotherapy in that normal body cells would not be targeted by our immune cells. The major advantage is that patients can be administered the vaccine in the pre-malignant stage, that is before the cells become cancerous. “The whole point of this is to reset the host, and not to focus killing the cancer,” says Finn. If trained to do so, our immune cells will take care of the latter job with ease.

The past century has been explosive for the field of medical oncology. Our understanding of cancer has grown and with it our ability to treat it. No longer is cancer viewed as an incurable disease. Survivorship rate is growing and with it comes knowledge of long-term effects of treatment, allowing us to further improve therapies. From mustine to Imatinib to cancer vaccines, we have traveled far. Hopefully one day all types of cancer will be viewed as curable and not life threatening. But Finn’s concluding remark during our interview is indeed remarkable, “None of this is necessary, if we focus on prevention.” Until then, we can help by contributing to cancer research, awareness, and prevention. Start by getting involved with Relay for Life, contact the local chapter of the Leukemia and Lymphoma Society, and the next time you think about cancer, think about humanity’s progress.

Visit the American Cancer Society’s webpage at www.cancer.org.

Pregnant with

DEBT:

How Midwives Deliver

Solutions to U.S. Health Care Costs Vivian Liang

W

hat is the most common and costly reason for hospitalization in the United States? Maternal and newborn care. Cesarean sections are the most common operating room procedure in the United States and are performed at a rate of 33 percent, which is excessive compared to the World Health Organizations’s recommended 15 percent.

The U.S. surpasses all other countries in maternal-newborn care costs. Cases vary in complexity, but a typical vaginal delivery costs $9,000, while a basic cesarean section can cost upwards of $15,000. According to the New York Times, in most other developed countries maternity care is either free or inexpensive. While many U.S. insurance plans cover a portion of the costs, women still have to pay a significant chunk out of pocket. Some women must pay entirely out of pocket if their insurance doesn’t cover these expenses. Caring for a child is already expensive enough, and prohibitive maternity costs create additional stress. The only hope of relief is through programs like Medical Assistance (also known as Medicaid).

Even though the U.S. spends the most on maternal care, it does not achieve the

Left to Right: Abby Rizk, CNM (midwife), clients with newborn baby.

best outcomes. Of the 34 organizations which belong to the Organization for Economic Cooperation and Development, the U.S. ranks 32nd in maternal and infant health outcomes. Furthermore, appreciable racial and ethnic disparities persist in access to quality maternal care.

According to the CDC, the group with the highest maternal and infant mortality rates is non-Hispanic blacks, with a rate 2.2 times higher than whites. In addition, inconsistencies in reporting race on birth certificates may underestimate the true infant mortality rates by race. The reality of the situation is more painful than the pain of labor, and it gives rise to the “perinatal paradox,” where spending more on birthing care doesn’t produce better outcomes.

The good news is that there is a viable solution to America’s “perinatal paradox.”

Midwives have been an under-utilized resource in America, and the experience is not all about delivering babies in a bath tub (although it is an option). Midwives, meaning “with woman,” are independent, certified health care providers who focus on a full range of women’s health needs, including gynecological care, family planning, and maternity care (before, during, and after childbirth). They partner with women from all walks of life to help them make informed choices about their maternity.

Midwives work in hospitals, medical offices, clinics, birth centers, and homes.

Having a baby at a birth center is extremely cost-effective. At The Midwife Center for Birth & Women’s Health, located in the Strip District, the cost to deliver a baby is around $2,500 on average, and most insurance plans cover midwife services. In general, birth centers accept clients who are low risk for complications during birth.

This way, the mother can save on the cost of expensive surgeons and anesthesiologists.

Furthermore, the midwives are very attentive to the mother and work with her by walking her around the room so that she can try out different positions to induce

A labor/delivery room.

labor. This method encourages a natural labor so costlier interventions can be avoided.

If there are complications, the woman is sent to the hospital (UPMC Mercy is the primary referral hospital for The Midwife Center for Birth & Women’s Health). Women who give birth at a birth center can expect to be discharged after 24 hours. For a hospital birth, the mother typically is required to stay for three days after giving birth, further driving up the service charges for maternal care. If 10 percent of current hospital births were held in a birth center, the U.S. would save $2.7 billion alone on service fees.

Even though Obamacare is expected to bridge the current coverage gap, it still may not be enough. Standard maternity care in America does not include benefits that would help new moms, such as breast-feeding education and basic training for newborn child-rearing. These are services that are integral to ensuring new mothers have everything they need to take care of their child. These are services that other developed countries include for free in their maternity care packages. It’s time to consider midwifery as an affordable alternative to hospital births.

It allows women to take charge of their birth experience, helps reduce strain on the U.S. health care system, and creates a bridge across the socio-economic disparities in women’s health. The unconventional alternative, in this case, may be the right one.

9

The Evolution of Lacta

By Abigail Wang

A

n ingredient in most dishes, milk is a food that humans are born with the ability to digest.

However, it is also the source of one of the most common food intolerances. For many people, the ability to digest milk is a shortlived faculty, gradually diminishing with the advent of adulthood. In fact, despite the popularity of milk products in today’s society, those who can digest it normally are in the minority. The majority—those who are sensitive to dairy—possess the trait commonly known as lactose intolerance.

Lactose intolerance is the inability to break down dairy sugar, or lactose.

To be lactose intolerant is to lack sufficient amounts of lactase, an enzyme

10

present in the small intestine. Lactase breaks lactose into smaller molecules which are more easily absorbed during digestion. Without lactase, individuals may experience nausea, abdominal pain, bloating, and other digestive issues upon ingestion of dairy products.

Less common than one might think, lactase persistence—or the ability to digest lactose—is only abundant in a few populations. Individuals with lactase persistence have the lactase enzyme and are therefore able to consume dairy products without any discomforting problems.

Studies of the lactase persistence trait have shown that it most frequently occurs in populations from northern

Europe, appearing in about ninety percent of individuals. However, only fifty percent of other Europeans and Middle Easterners and less than ten percent of Asians possess the lactase persistence trait. While the trait is common in parts of Africa that rely on pastoral farming (where they use milk as a primary nutrient source), other African populations experience relatively low rates of lactase persistence. In all, only thirty-five percent of the world population can digest dairy.

Though lactose intolerance is widely perceived as an allergy that developed over hundreds of years, the inability to digest lactose into adulthood is a chronologically older condition. That is, lactase persistence appeared later, in evolutionary terms, particularly in populations that relied heavily on agricultural means of food production.

Early humans could not digest dairy into adulthood at all, and the appearance of lactase persistence evolved by natural

ase Persistence

selection over a span of thousands of years.

A dominant trait, lactase persistence arises from the expression of a particular gene that encodes for lactase. The most common root of the geneâ&#x20AC;&#x2122;s expression is a variation in a single nucleotideâ&#x20AC;&#x201D;or one link in the long chain responsible for protein productionâ&#x20AC;&#x201D;that found its way into the human race and nurtured the dependence on dairy that exists in many societies today.

As noted above, lactase persistence occurs most commonly in populations that rely heavily on dairy farming.

Thus, dairy consumption and lactase persistence grew side by side.

The question remains: was dairy farming adopted because these populations had the ability to digest milk products?

Or did the lactase persistent trait become favored by natural selection in response to the rise in dairy farming? A 2006 study conducted by genetic researcher Sarah Tishkoff favors the latter hypothesis.

Analyzing DNA from ancient

Neolithic and Mesolithic hunter-gatherer skeletons, Tishkoff and her team found a low frequency of the lactase persistence gene, suggesting that early pastoralist populations had not yet shown a high prevalence of lactase-digesting ability.

It is likely that lactase persistence became more common in populations after dairy farming was introduced, and the ability to drink milk and garner its health benefits resulted in a selective advantage for the lactase persistence trait.

Despite the prevalence of lactose intolerance, most people continue to relish dairy products, whether in deliberate disregard or simple ignorance of their hypersensitivity. Lactose intolerance is not an allergy; food allergy involves an immune reaction in response to an ingestion of something normally harmless, whereas a food intolerance, conversely, indicates an inability (or decreased ability) to digest a certain food. Food intolerance can be mild enough to be almost unnoticeable with

small amounts of the food, so many people ignore the adverse side effects and continue to consume lactose. Furthermore, popular dairy products like cheese and yogurt have already undergone fermentation in their production processes, and much of the lactose is already broken down, rendering these products agreeable with the digestive systems of lactose intolerant individuals.

While lactose intolerance is still widely prevalent today, the modern availability of much-cherished products like milk, ice cream, and butter is nevertheless thanks to the emergence of lactase persistence that has its roots in ancient populations. Appreciating the fact that the ability to drink milk has only been around for a few thousand years can raise questions about the prevalence of other food sensitivities at the intersection of history, culture, and biology.

11

did that

ACTUALLY happen?

LIGHT SHEDDING

ON

FA L S E M E M O R I E S B Y M A N I S HA K I N TA L I

In 1994, Elizabeth Loftus, a cognitive psychologist, was able to implant into a quarter of her subjects a memory of being lost and in panic in a mall as a child and eventually being rescued by an elderly person who reunited them with their parent. This experiment was purely psychological, but is it possible to actually implant a memory of this nature physiologically? These types of experiments call to mind certain popular films like Inception, but a study conducted this past summer might be just as mind-bending and fascinating.

In July of 2013, Steve Ramirez and Xu Liu from the MIT lab of Susumu Tonegawa, a 1987 Nobel Prize winner for Medicine or Physiology, were able to successfully create false memories in the hippocampus of mice. False memories are memories of events that never actually happened or distorted memories resulting from the influence of external events or the feeding of new, suggestive information.

“What if we can start off by going into the brain and finding a single memory to begin with? Can we jumpstart that memory back to life? Maybe even play with the contents of that memory?” asked Ramirez while giving a TEDx talk in Boston in June of 2013.

So, that’s exactly what they did first—Ramirez and Liu found a way to target a single memory. In April of 2012, they published a paper in the journal, Nature describing their successful attempt to reactivate a fear memory in mice by using a new technology called optogenetic stimulation.

12

Figure 1. Fear Memory Recall

Box B

Box A •

Habituation of light stimulation

• •

Fear conditioning Cells encoding fear memory are labelled with ChR2

Box A • • •

Optogenetics uses, as the name suggests, genetics and light to target and control the activity of specific cells under focus. In 2002, an opsin, or a light-sensitive membrane protein, by the name of channelrhodoposin (ChR2) was discovered. The gene of this opsin is installed into targeted neurons, which consequently express ChR2.

Then, when blue visible light is applied to those cells, the protein channels open up creating a flux of ions resulting in activation. This gives the experimenters freedom to turn neurons “on” and “off ” with ChR2 essentially functioning like a switch in response to the presence of light. It provides scientists specificity, easy targeting, and less damage than using conventional electrical stimulation techniques.

Using this groundbreaking technique, ChR2 was packed into a genetically engineered virus and was injected into the hippocampus, the center for memory formation, of mice. More specifically, Ramirez and Liu were targeting a subpopulation of granule cells located in the dentate gyrus of the hippocampus where contextual aspects of memory can be traced. These cells are thus identified as contextual memory-engram cells.

For the first five days, the mice were put in Box A to become habituated with light-stimulation and were on a doxycycline (Dox) diet. Dox was used to prevent the cells from being labeled with ChR2. So while in Box A, the cells that were encoding the contextual memory of A weren’t expressing ChR2. The mice were then taken off Dox for the next two days and were put in a different box, Box B, where they were fear-conditioned by receiving foot shocks. This time, the cells encoding the memory of the foot shock were now labeled with ChR2, making it easier to access and control those cells for testing. Mice were put back in Box A, to test for fear memory recall by shining blue light using an optic-fiber onto the labeled cells. When stimulated with light, the mice froze in Box A indicating

Optogenetic stimulation Fear memory encoded ChR2labelled mice are reactivated Mice freeze

that the neurons that were active during fear memory encoding while in Box B were indeed reactivated. (Fig 1) But, during the summer of 2012, Ramirez and Liu delved further into a more manipulative task to answer their last question, “What if we reactivate a memory but tinker with it and possibly make into a false memory?”

In this study, mice were once again injected with a virus carrying ChR2 into the dentate gyrus and were implanted with optic fibers. After recovering from the surgery, the mice were put in Box A and were off the Dox diet. They were allowed to encode the contextual memory of Box A and consequently these cells became labeled with ChR2.

Following which they were put back on the Dox diet and were placed in a new environment called Box B. While in Box B, the mice received foot shocks (fear-conditioning) and the labeled cells from Box A, cells that were labeled with ChR2 while encoding the contextual memory of Box A, were reactivated by shining blue light through the optic fiber. Lastly, the mice were put back into Box A and observed the mice freezing in place expressing fear. (Fig 2) What happened? Why did the mice become afraid of Box A when that wasn’t where they received the foot shock?

When the ChR2 labeled cells from Box A were reactivated, the contextual memory of Box A became associated with the fear memory that was being encoded from the simultaneous foot shocks the mice were receiving. This led to the distortion of the contextual memory of Box A resulting in a new memory, a false memory. Subsequently, the mice froze when put back into Box A because they thought that was where they received the foot shock when in reality, this environment never posed a threat to them.

This goes to show the vulnerability of memories and how easily modifiable they are. The implications of false memories are tremendous, having huge impact in many real-time situations such as when giving testimonials to the court.

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Figure 2. Creating False Memories

Box B

Box A • •

Develop contextual memory of Box A Cells are labelled with ChR2

• • •

Fear conditioning and simultaneous reactivation of ChR2 labelled cells Fear memory becomes associated with memeory of Box A False Memory?

In 1983, the McMartin Preschool, CA was charged with a sexual abuse case, prosecuting several McMartin family members and teachers of sexually abusing the children. The trial lasted seven years and cost $15 million making it the longest and most expensive criminal case in the US. In 1990, all the charges were dropped and no one ended up convicted. It was found that the abuse therapists interviewing the children fed them with suggestive information leading them to develop false memories of sexual abuse they never experienced. These videotaped interviews were crucial for the defense and influential in the jury’s refusal to convict.

When asked about any advantages of memories being easily alterable, Dr. Germán Barrionuevo, a Neuroscience professor here at Pitt whose lab extensively studies the hippocampus, said, “The reconsolidation process of memories is useful when adapting to a new situation. ato fit the needs of the new environment.”

Reconsolidation is a recently developed hypothesis on how memories are stored. Once memories are formed, they become labile and the engram (memory trace) can be reorganized through synaptic and system organization creating long-term memories and distributing them throughout the neo-cortex.

However, when that consolidated memory is recalled, it once again becomes labile and can be modified. Once that memory is modified, it is then reconsolidated.

14

Box •

Mice freeze = Successful creation of false memory

The reconsolidation hypothesis and the study’s findings may provide ways on how false memories can have clinical applications. Dr. Floh Thiels, a Pitt associate professor of Neurobiology, said “We can use this to maybe treat PTSD for soldiers or people who have gone through a traumatic experience. It can also be used for memory-based anxiety disorders by pairing the activation pattern of those memories with something pleasurable to provide relief.”

However this poses technical issues when trying to activate these memories of humans. Ramirez and Liu used optogenetic stimulation on mice but this technique hasn’t been tested on humans as of yet and will take a long time to get it approved for clinical use. But when it does, optogenetics with false memories can be an instrumental tool for treating psychiatric disorders or learning more about the brain circuitry and specifically to memory formation.

“It’ll be interesting to see if the process of creating false memories recruits the same machinery that was used for creating the original memory,” said Dr. Thiels when asked about how she would take this research forward.

Even without taking this research forward, however it will be a shame not to, this study provided the first direct experimental evidence that false memories can be created physiologically. The significance of the findings is extraordinary and not to mention, can be a basis for another great Christopher Nolan movie.

O

n October 8th, the world echoed the cheers of CERN for Peter Higgs as he received the Nobel Prize in physics. BBC’s Craig Williams calls him, “the man behind one of the most remarkable scientific ideas of the past fifty years.” The Guardian and many others know him as, “the father of the [so-called] ‘God Particle.’” But what has Peter Higgs done to earn a title as prestigious as a Nobel Prize Laureate? The enormous mystery of where subatomic particles acquire their mass has been puzzling scientists of all denominations for decades. However, thanks to the Higgs boson theory and the nearly incomprehensible work amassed from decades of research by the European Organization for Nuclear Research (CERN), we may finally have our answer.

This incredible concept started with Peter Higgs’ first theory in 1964, known as the “Higgs Field.” As described by The Guardian scientific correspondent Ian Sample, the Higgs field is a phenomenon that came into effect a trillionth of a second after the Big Bang, before which subatomic particles traveled at the speed of light.

Once the Higgs Field came into effect, the field began to slow different particles in accordance with the amount of interaction that each particle had with the field. By this logic, mass should be seen as its proper definition – an attraction between two forces (gravity’s pull on an object). Don Lincoln, in a TED-Ed Lecture, explains a comprehensible analogy of this field: think of the field as a group of scientists in a room. When someone like a tax collector comes in, nobody talks to him and he passes easily through the crowd; however, when someone like Peter Higgs enters the room, the scientists cluster around him and slow him down as he walks through the room. The group of scientists represent the Higgs Field, the tax collector a low-mass particle such as an electron,

15

and Peter Higgs a heavy weight particle such as a “top quark.” But how does the Higgs boson fit into this?

The Higgs boson, according to Lincoln’s analogy, would be like a rumor traveling from one end of the party to the other. Essentially, the Higgs boson is a cluster of the Higgs field traveling across itself, making its way throughout the party. Daniel Whiteson, a physicist at CERN, explains that this particle is actively sought via scientific data because its existence would prove Higgs’ theory of subatomic mass. This is done with an enormous machine known as the “Large Hadron Collider,” which lies in an elliptical 27 kilometer-long tunnel. This scientifically revolutionary machine bombards subatomic particles together, creating a contained (but massive) explosion of energy, which in turn releases new particles. The Higgs boson is suspected to be an “intermediate” in one of these reactions, being created after the bombardment of two particles, but then quickly decaying after 1.0 x 10-23 seconds into other (more common) subatomic particles.

The great obstacle that makes the discovery of this intermediate so difficult is that the bombardment cannot be observed directly; the only known information includes the identification of the bombarded particles, the particles produced at the end of the process, and the total energy of the reaction. Leon Lenderman, an American Physicist, coined the term “god particle” for the Higgs boson for this exact reason—though it is so fundamental for the understanding of the world as we know it, the particle is entirely elusive. So, to discover the high probability of the particle, the collider is run constantly, performing bombardment after bombardment, 40 million times per second, every second of the year, creating an enormous amount of data. This data is compared to the calculated information of what the data would look like with and without the particle’s presence.

On March 14, 2013, the particle was confirmed with 99% certainty. Higgs’ theory, which potentially solved the mystery of mass, was proved to be true, at least as close to true as we can possibly get, and a Nobel Prize was certainly in line.

Though the discovery was an enormous milestone to science, its future remains uncertain. Many scientists consider this discovery to be bittersweet in nature, because further research has not been developed or considered. Wired journalist Adam Mann explains that, “while popular articles often describe how the Higgs might help theorists investigating the weird worlds of string theory, multiple universes, or supersymmetry, the truth is that evidence for these ideas is scant to nonexistent.” This, however, is the real basis of science. There is no “end of the rope” for any given concept; theories are constantly extended, compared, retested, or flat-out disproven. So, rather than accept the theory and move on, we should ask ourselves, “what more can we do.”

Admirably functioning

personal relationships rarely are considered as effects of our human biology, but our ability to function as a team of two relies on more than just personality. Although the development of personal preference and disposition make relationships more complex, many couples donâ&#x20AC;&#x2122;t realize that healthy relationships function well based on biological evolution and the way our brains are wired.

In the context of male-female relationships, there are important traits that distinguish the female brain from the male brain. Structurally, the female brain has a larger prefrontal cortex (PFC), insula, hippocampus, and anterior cingulate cortex (ACC). The PFC controls the emotions of the brain and also the amygdala, which contains ideas of instinctual behavior. The insula processes the gut feelings, the hippocampus stores memories, and the ACC controls decision making. Apart from being structurally larger, these areas of the brain are also more active in females. Scientists believe that in the male brain, the temporal parietal

junction (TPJ), and rostral cingulated zone (RCZ) are the centers of brain activity in social situations. The TPJ is more active in the male brain and is responsible for problem solving, and the RCZ accounts for what is socially accepted and unaccepted.

In the context of a relationship, women are in search for a mate that will provide them with love and stability.

That seems pretty obvious, but the scientific explanation is less so. To find the answer, we begin thousands of years ago with our pre-historic ancestors. Since the gestation period for humans is nine months, our ancestral female relatives were searching for males that would protect them through the nine months of pregnancy. Even though the human brain has evolved since ancient times, the female brain has retained some of that ancient hardwiring, explaining why women search for a suitable mate that will provide them with stability. A preference among women for taller, athletic men, may stem from this past evolutionary desire.

Like females, males also have their ancestral hardwiring intact. The goal for our pre-historic ancestors, like living

beings of any species, was to reproduce to pass on their genes. For males, this meant reproduction with a fertile female.

Louann Brizendine, M.D., discusses in her book, The Female Brain, the â&#x20AC;&#x153;visual cluesâ&#x20AC;? of fertility and health. Young and energetic women with smooth skin, symmetrical corporeal features, radiant hair, plump lips, and an hourglass figure with bigger breasts are seen as more fertile. These traits are signs of high levels of estrogen, and thus tend to attract more men because the male brain has evolved to associate these features with reproductive health. Similar to females who look for muscular males because their brain is subconsciously looking for someone who will provide them with safety and stability, males subliminally look for females with high fertility levels in order to propagate their genes.

Both males and females subconsciously chose their partners based on their physical features and in the hopes of finding the best genes to breed with. Females generally look for physically strong males who can provide security during the months of pregnancy, while males

strive to pass on their genes by looking for fertile females. Although it may be clear what characteristics males and females look for in their partner, how can they possibly know where to find “the one”?

In her second book, The Male Brain, Brizendine compares the male mating styles to the mating tactics of the sideblotched lizard. Each lizard of the male gender has a different colored throat that corresponds to the lizard’s mating style. The orange throats use a tactic described by Brizendine as an “alphamale harem strategy.” This lizard has his own clan of female lizards that he constantly mates with. We can equivocate the orange-throated lizard to the typical womanizer—a guy who’s just not willing to leave bachelorhood. There are also, however, side-blotched lizards with blue throats. These lizards are the so-called “one” because they choose to couple with and protect one female. But why are certain males, as Brizendine states, “confirmed bachelors,” while the others are caring monogamous partners? In a Swedish study, it was uncovered that men whose genetic code contained a longer coding region for

the vasopressin receptor were more likely to settle down than remain unattached. If a female is searching for a monogamous partner, these are the ones to look for.

When the female brain falls in love, hormones and neurochemicals like estrogen, testosterone, dopamine, and oxytocin flood the brain. This reaction is similar to what occurs in the male brain, except the dopamine would be mixed with testosterone and vasopressin. This rush of neurochemicals and hormones is analogous to the initial effects of drugs.

It can cause people to become addicted to their lover in the early months of the relationship and will continue on for six to eight months. The release of oxytocin and dopamine in females are produced by physical interaction, even something as simple as hugging, causing them to feel as if their partner is a drug and they cannot live without him. A woman could just see the man that she has been romantically involved with and oxytocin can be released into her brain. Similarly for men, testosterone and physical interactions fuel the production of vasopressin, causing an enhancement in awareness, energy, and

aggression. This surge of testosterone and vasopressin hormone can cause the ancestral possessive and territorial alphamale to emerge. These hormones alert him of the danger of having his mate “stolen” due the surge of activity in the “fear-of-rejection center,” (as Brizendine describes) located in the amygdala and the “mating area” in the hypothalamus. The emergence of the alpha-male shows that males in love strive to protect their mates, which leads them to become possessive.

Modern humans underestimate the science involved in relationships.

We have feelings and personal desires, preferences and contextual limitations that prevent some relationships and create others. With the evolution of the human species come different criteria for searching for mates apart from body type.

Furthermore, many people find their humanity in their partner. As said aptly by Pitt student Claire Schafer, it “gives your life meaning,” in a sometimes seemingly inconsequential world. Whether this is the effect of dopamine and/or vasopressin, or the product of personal values, people are still on the search for the “one.”

Holmes

Antiseptic Medicine

The History of

F

rom groundbreaking research to clinical care, the practice of medicine has evolved, and the history of this evolution provides interesting insight into certain health protocols that many of us take for granted. Sanitation, amongst both the general population and healthcare professionals, has only been in use for about 150 years. The history of antisepsis first began with three wellknown physicians: Oliver Wendell Holmes, Ignaz Semmelweis, and Joseph Lister.

In Boston, 1843, Oliver Wendell Holmes discovered that a certain fever, known as puerperal fever, passed from patient to patient when the physician’s hands were unclean, a phenomenon with a high mortality rate which he first recognized in pregnant women. As a result of this fever, Holmes published, “The Contagiousness of Puerperal Fever,” in the New England Quarterly Journal of Medicine and Surgery, which postulated the theory of contagion, stating that disease could be passed between individuals through contact. However, the development of antisepsis was not initiated because many physicians were

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Vighnesh Viswanathan not interested in refining their procedures.

Within the year, Ignaz Semmelweis also remarked on the persistence of puerperal fever in pregnant women in Vienna. This provided him with the great opportunity to point out, like Oliver Wendell Holmes did, that the fever spread from the infected hands of the physician to the patient, and that the fever would eventually spread from patient to patient. He postulated that there was some “cadaverous material” causing this fever after assessing that the fever originated from the doctor’s hand. To rectify the issue, Semmelweis suggested that the doctors wash their hands with chlorinated lime solutions in order to keep themselves hygienic, and he is now considered the father for the introduction of hand-washing disinfectants.

Ironically, Semmelweis died due to mental complications of septicemia, but he is nevertheless a venerated figure in the history of medicine.

Joseph Lister was a surgeon from Scotland who played a very important role in developing antiseptic protocols for operating rooms. His first contribution was the use of gloves when operating on a

patient. He further added to the antiseptic tradition in 1867 when he initiated the application of carbolic acids on wounds and openings to prevent infections and pathogens from entering the body.

The three predominant figures that contributed to the initiation of antiseptic protocols all made their discoveries around the same time, and who made the discovery first is still a controversial topic. Gerald Weissman, author of “Puerperal Priority” (published in the English journal The Lancet) writes: “England honors Lister for antisepsis, Europeans acclaim Semmelweis for the aetiology and prophylaxis of puerperal fever, and the USA gives priority to Oliver Wendell Holmes.” Although many contemporary historians of science would like to credit one or another specific physician with revolutionizing the way we approach hygienics, each of the three medical giants provided massive contributions. Next time you wash your hands, instead of singing “row, row, row your boat” (a technique taught to many health students as a way of ensuring clean hands), thank Holmes, Semmelweis, and Lister once for each clean finger.

BREAKING BARRIER the

A

Commentary on David Biro’s Listening to Pain

I

remember going to the hospital with a torn meniscus in high school. The knee pain was unbearable, and I had tears streaming down my face as I hobbled into the ER. I sat there, rocking back and forth, icing my knee as I clutched it, hoping I could stop the pain from spreading.

The ER doctor walked in and started the examination. After greeting me he asked, “How would you rate your pain on a scale of 1 to 10?” I wanted to yell out, “A billion!!

Are you crazy, I’m crying from pain! Why would you even ask that?!” Yet, I tried to push through the pain and replied with a tentative 8. Did I know what pain ‘1’ or ‘10’ felt like? No way! I surmised; it wasn’t the worst pain I had felt so it couldn’t be the highest value. With that useless bit of information, he could do nothing. Why ask me that question anyways? Besides logging it onto a chart, what does that information truly provide him? Does he know the true magnitude of my pain? Will he prescribe the correct dosage of pain killers?

In moments like this I bemoan the state of patient-doctor interactions. Enough is enough. It is time to think beyond pointing to cartoon faces of pain or asking patients to rank their pain on a scale of 1 to 10. We must delve deeper to understand the concept of patient pain as a unique phenomenon capable of building a barrier between the patient and the physician.

David Biro’s Listening to Pain is a guide to understanding a patient’s suffering. A

Rashmi Kumar

practicing physician and a cancer survivor who received a bone marrow transplant, Biro is a fantastic leader into the unknown world of pain as both an emotional and physical response. His book captures a sense of yearning to find a fitting way to describe pain. Listening to Pain uses metaphorical language to find a way to relate to patients in ways physicians have not before.

I originally had reservations about this idea; metaphorical language, in my mind, is a literary device that is usually analyzed in a novel, poem, or other prose. However, Biro illuminates that metaphorical language is all around us. When we say, “I feel a stabbing pain,” this is a metaphor. When we say, “the tumor invaded and spread everywhere to conquer other organs,” we are personifying a disease. Through metaphor, we speak about pain even when it often has the capacity to silence us. In these cases, our pain is unheard, and Biro remarks that there is an alarming amount of patient cases in which the prescribed pain medication is insufficient due to a misunderstanding of the depth of the pain.

To this, my follow-up question was, “if we are capable of creating metaphors, why are doctors and patients unable to communicate through them?” Biro suggests that it is the curse of repetition. The same metaphor of a “stabbing” pain has been used so often that the metaphor itself has become defunct. Inherently, this is a limitation of using metaphors. The communicated in-

17

tensity of the pain is dulled in the same way the metaphorical image of a stabbing pain has dulled through overuse. Biro suggests that we must constantly “reinvent” and be imaginative with our metaphors. He describes a scenario from a published novel in which a young boy describes his ear pain metaphorically. Children speak metaphorically with the utmost instinct because they do not have the extended vocabulary of adults; therefore they compare and link their experiences to everyday encounters with a distinct sort of ease. The young boy in the book describes the roar in his ear as similar to the sound of a train rushing through a tunnel.

While to some it may seem silly that we would describe pain with such figurative language, it seems far sillier to be shown pictures of five faces in pain and asked to point to the one you feel most like.

How can we construct metaphors to describe our pain? It is all well and easy when a character from a novel or author is describing their pain metaphorically, but how can everyday people accomplish this? Here, Biro’s book fails to give a detailed account of creating metaphors. What he focuses on instead is allowing the patient to be aware of another form of communication, and requesting doctors to be more conscientious of listening to patients as they employ these metaphors. Perhaps by stopping short of providing a list of metaphors to use, Biro is practicing what he preaches. He does not want to become categorical or repetitive about describing pain.

It is relevant to point out that Biro does not focus on emotional pain, which is a distinct entity from physical pain that requires different metaphors. Emotional pain must be externalized with language for it to be recognized, and it can even be more difficult to deal with emotional anguish

18

than physical pain, which can sometimes be taken care of with Tylenol or Advil. Physical pain is also fleeting, and our body is conditioned to forget such pain. A prime example is labor pains in women. If these memories of physical pain were not selectively repressed, women would cease to have children. Emotional pain, however, is lingering and harder to access because of how it adapts, builds, and seems to grow over the years. Biro’s book is more concerned with physical pain rather than emotional pain, perhaps because people are more willing to discuss the former to get immediate relief than the latter, making his ideas about using metaphorical language more applicable and informative. In any case, pain is a dichotomous force capable of emotional and physical effects.

This being said, it becomes even more critical that we find a way to understand patient pain.

David Biro’s Listening to Pain is an incredible read that can open your mind to a culprit that ails all patients. Biro suggests that as long as there is communication, the barrier will remain breach-able.

Biro’s book is a metaphysical ride that forces us to think about the origin of pain, our own battles with both physical or emotional pain, and to examine the words we unknowingly use to communicate what we feel. While it leaves some lingering questions, they are the kind that we have been grappling to answer for decades, and Biro takes us a step closer to breaking the barrier between the patient and the physician. In Biro’s metaphorical fashion, I would say his book is a shaft of light into the dark recesses of an innate human response and is a suggested read for those interested not only in medicine, but also language, communication, and the way internal conditions affect interpersonal relationships.

Left: Program Coordinator Anneliese Murphree To Apply to CCNMD for Summer 2014, visit www.CCNMD.pitt.edu!

Applications are due on February 7th, 2014.

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THE AFFORDABLE C

BY JASON NAUGHTON

I

f you’ve been living under a rock these past few weeks that is probably because your house has been repossessed by a herd of wildebeests in the backlash of the government shutdown, and you have been forced to live amongst the cave people. Yet even then you have come to know the horror— the terror!—that is the Affordable Care Act (ACA).

If alarmist rhetoric is to be trusted, “Obamacare” falls somewhere between an economic rectal exam—unpleasant but wholly well-intentioned—and Hitler’s Third Reich. Rep. Todd Rokita (R-IN) called Obamacare “one of the most insidious laws ever created by man.” Likewise, Rep. Michelle Bachmann (R-MN), warned that the Affordable Care Act—or “DeathCare,” as she would prefer—will turn the country into a “police state.” Fox news contributor and retired neurosurgeon Ben Carson furthered this sentiment in calling Obamacare “[the] worst thing that has happened in this nation since slavery.”

And finally, Rep. Brenda Barton (R-AZ) reminded the nation to “read your history. Germany started with national health care…before [the Holocaust].”

Now this bumbling atrocity is drooling down our necks, and after a brinksmanship backfire within Congress, Tea Party conservatives—our final hope for salvation—have abandoned their post.

So what is this nightmare that is at our doorstep? What is this hell-born Nazi socialist plague that seeks to loot our apple pie and pillage our Fonzies?

And what does this fire and brimstone mean to you as a student?

In short: probably nothing.

Yes, it’s true, between the volcanic pterodactyls that patrol our skies, and the demonic hound-beast that scours the streets at night, it may be inconvenient to get to class. However, you might find the brute’s bark worse than his bite.

Opponents of the bill will tell you that you must get health insurance by January 1, 2014, or you will be forced to pay an egregious ($95) fine. This is not completely true. This “individual mandate” clause only applies to people who earn enough to file income taxes, or $9,700 a year. Although many students dream about this “dilemma,” it is likely not applicable.

Others will tell you that you will be forced to drop your existing healthcare plan and enroll in this socialist coverage. Again, this is simply not true. Students are more than welcome to shop for health care on the open market, or to retain their prior healthcare benefits. Likewise, the University of Pittsburgh’s healthcare plan is still a viable option, as is your existing private insurance plan, assuming it complies with the minimum coverage requirements of the ACA. In fact, a provision of the ACA demands that insurance companies allow students to be insured within their parent’s healthcare plan until they are 26 years old. This will likely save a substantial majority from finding their own healthcare until they have a steady job, as compared to finding cheap premiums immediately upon graduation. This provision applies even if the student is married, not living with or financially dependent on his/her parents, eligible

22

CARE ACT AND YOU to enroll in his/her employer’s plan, or all of the above.

Again, that said, students may not want their parents’ plan. This is the case for many students who study away from their parents’ work place—say, if the parents work in Philly and the student attends Pitt—in which case much of the insurance network is removed from their vicinity. Well, assuming you can log on to the site, there are a number of low-cost governmental healthcare options available to students. In fact, The Department of Health and Human Services released a report in October stating that “46 percent of uninsured young adults in single-person households may be able to purchase a bronze plan for $50 per month or less after tax credits.” Students in certain unfortunate economic situations may even qualify for the expanded Medicaid benefits, which would affordably cover a number of common health discrepancies.

(However, as the great Commonwealth of Pennsylvania has denied Medicaid expansion under the provisions of the recent Supreme Court ruling on the ACA, these students would not likely be wearing Panther blue.)

Let’s just say that all else has failed: your parents are not covered, your former private insurance does not meet the minimum care requirements, your state has denied expanded Medicaid benefits, your university’s premiums are too high, and you make over $10,000 a year—none of which you would like to pay towards healthcare. Even then the “catastrophic” health plan is available to most applicants under 30. This plan has a substantially lower premium but requires you to pay all your medical costs up to a certain amount (usually several thousand dollars) out of pocket, leaving the insurance company responsible for essential health benefits over that amount. For the most part, rather than spend your well-earned money on something as frivolous as health insurance, you may instead address the medical billings directly, just as you had before this evil plagued the nation, only now with an insurance safeguard against egregious medical charges.

There is some hyperbolic postulation that the negative economic effects of the ACA will trickle down to students. Pundits banter over whether your parents will lose their coverage and work hours to account for the measures on businesses to insure all full-time workers. Others theorize that insurance companies will somehow begin to offer higher premiums to combat the low rates offered by the government, in some kind of funhouse mirror economic system. And still others say that your college degree will be useless anyway, as you will be graduating into a nuclear garbage wasteland perpetuated by this catastrophic bill, the likes of which may only be traversed by Kurt Russell’s ‘80s mullet.

However, assuming you can battle past the hordes of howler monkeys that stalk the charred remnants of what used to be our hospitals, you may be left with naught but a sticker, a lollipop, and a smiling nurse glancing up from her charts asking: “That wasn’t so bad, now, was it?”

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VOLUME IV ISSUE II || DECEMBER 2013

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