Fall 2013: Volume 6, Issue 1

The Amherst

ELEMENT Volume 6, 1, Issue 1 2

November Fall 1, 2007 2013

Letter from the Editor Thank you for picking up the Fall 2013 edition of The Amherst Element! Thanks to all the writers and editors who contributed! And I want to mention Sonum Dixit and David Nam for their help and support. This semester, we offer articles in medicine (Advances in Kidney Transplantations by Thomas Savage ’15), neuroscience (Fluorescence, Hearing, and Zebrafish by Azka Javaid ‘17), genetic engineering (Minicircles by Minjee Kim ‘17), and botany (Carnivorous Plants by Lindsey Bechen ‘16; Coca and its Effects by Kevin Mei ‘16) and an interview with Professor Loinaz of the physics department by Ji Hoon Lee ‘16.

Seven years ago in the first issue of The Element, Editor-in-Chief Melissa Moulton wrote a decisively worded editorial addressing scientific literacy on campus. “Many of today’s most important topics– stem cell research, oil dependency, climate change, and genetic engineering– defy intelligent analysis without a solid grounding in basic scientific principles.”

Today, that list only grows with the advent of discoveries in medicine (gene therapy, tissue engineering) and technology (Bitcoin, government “spying”). “It is unsettling that many Americans, including many elected officials, are unequipped to differentiate solid scientific ideas from pseudoscience,” writes Melissa.

Yet most popular and convenient resources remain pseudo-scientific expositions. Especially in the field of neuroscience, findings often lead to runaway conclusions. Lingering misconceptions (that “we only use 10% of our brains”) persist. Science sections in bookstores are replete with books purporting to explain the brain and how you can improve your creativity, motivation, or thinking. I want to reinforce Melissa’s message to seek scientific literacy while also encouraging resistance to speculative information. Be resistant as to what you believe from self-help books, health articles, or what is shared on social networks. By no means are popular resources bad (I love a good Malcolm Gladwell story), but references to some studies (cognitive psychology for example) and quoting some scientists often lead to a misinterpretation or impression of truth that may not be valid. Even published scientific articles are contested (as in the News-in-Brief). In this information age, a healthy skepticism, which may or may not accompany scientific literacy, is invaluable. It remains the goal of The Element to continue to promote informed scientific discourse.

Sincerely,

Kevin Mei

News-In-Brief Kevin Mei ‘16 Pluripotentency in Cells Triggered by Physical Stimulus The study of stem cells has come far from the days when there was controversy over scientific use of embryonic stem cells.

Takahashi and Yamanaka found that by genetically inserting four stem cell regulatory factors into adult differentiated cells, pluripotency (the ability to develop into any cell type) could be induced. Now, in a recent Nature article, Obokata et al. found that pluripotency in mice can be triggered by low pH and they termed this change as stimulus-triggered acquisition of pluripotency (STAP). The researchers exposed differentiated white blood cells from recently born mice to a mildly acidic solution and found that the cells lost their differentiated state.

STAP cells cannot self-renew but by being grown in stem cell media, acquire self-renewal and other properties of stem cell; they become STAP stem cells. After injection of these cells into mice embryos, stable cells of different tissue types formed

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from both the host cells and the STAP stem cells. This is a novel discovery because genetic manipulation was not involved! A physical environmental stimulus triggered pluripotency. How do cells normally suppress pluripotency and how and why does this mechanism exist to activate pluripotency under a different physical environment? If a simple procedure for stimulustriggered pluripotency can be found, obtaining stem cells would become both cheaper and more efficient. [Edit: At the time of writing, this article has generated some controversy because of reports of unreproducible protocols and results.]

Table of Contents

The Amherst Element Staff Editors-in-Chief Kevin Mei Thomas Savage

Associate Copy Editors Lindsey Bechen Sonum Dixit Azka Javaid Minjee Kim David Nam Chanyoung Park

Layout Azka Javaid Minjee Kim David Nam Get Involved!

Send questions, comments, letters, or submissions to theAmherstElement@ gmail.com.

Call For Writers!

The Amherst Element is looking for more writers and contributors!

We’re always looking for diversity! We welcome writers from all backgrounds from computer science and math to the humanities.

Please feel free to submit articles regardless of your background!

Cover Features 1 Artificial Life Eugene Lee ‘16 20 Bug’s Life Eugene Lee ‘16

Features

2 News-in-Brief

Kevin Mei ‘16

18 Interview with Professor Loinaz Ji Hoon Lee ‘16

Letters 4

Carnivorous Plants

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Advances in Kidney Transplantation

Lindsey Bechen ‘16

Thomas Savage ‘15 9 Minicircles Minjee Kim ‘17 12 Coca and its Effects

Kevin Mei ‘16 15

Flourescence, Hearing, and Zebrafish

Azka Javaid ‘17

If thesis students would like to be write about their research or are willing to be interviewed, please contact us!

The opinions and ideas expressed in The Element are those of the individual writers and do not necessarily reflect the views of The Element or Amherst College. The editorials are a product of the opinions of the current editors-in-chief of The Element. The Element does not discriminate on the basis of gender, race, ethnicity, sexual orientation, scientific background, or age.

Research findings published in The Element are not intended for wide distribution or for the reader’s profit. As a member of the Amherst community, please use the information and data presented in The Element judiciously.

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Letters

Carnivorous Plants Lindsey Bechen ‘16

Introduction On first glance, most plants seem like gentle, harmless organisms. With the exception of poisonous or thorny plants, this is perhaps true. While many people are familiar with the famous Venus Flytrap, there are a variety of carnivorous plant species, employing a wide range of traps and digestive techniques.

To be considered carnivorous, a plant must capture and kill its prey, use enzymes or bacteria to digest the meal, and benefit from the nutrients it receives from digestion. There are plants that trap insects in their flowers to aid pollination, such as some species of Aroid and Aristolochia, and a few of the insects may die as a result.

However, these plants are not considered carnivorous because they derive no benefit from the dead insects.1 Types of Traps Pitfall: Pitfall traps, commonly found in pitcher plants, are made from leaves folded into a curved shape, with pools of digestive enzymes at the bottom.2 Insects that fall into these traps are unable to escape, especially because some plants also secrete a slippery substance that prevents them from climbing out. Some species of these pitcher plants are large enough to capture and digest a frog or rat.3 (See Figure 1).

Flypaper: Perhaps the simplest of the mechanisms, flypaper traps use variations of sticky leaves to capture their prey. Glands positioned on little stalks secrete thick, sticky mucilage which traps prey that comes into contact with it.2 Snap: Snap traps use hinged leaves that snap shut when triggered by prey.2 The Venus Flytrap, the most well known of the carnivorous plants, belongs to this category. (See Figure 2). The Venus Flytrap’s mechanism works in an astonishing and unexpected way. There are tiny hairs on the surface of the trap that, when triggered, build up an electrical charge. It takes two triggers of the hairs within 35 seconds of each other to set off the trap, because it is only then that the electrical charge is great enough to pass the threshold and create an action potential.4 The action potential travels from the hairs to the center of the trap, where it triggers the opening of aquaporins in the cell wall. When the trap is open, the top layer of cells has a very high water pressure or turgor. When the aquaporins are opened, water rushes to equilibrate the top and bottom layer of cells. This causes an abrupt change in the curve of the leaf from convex to concave, which closes the trap.5 When digestion is finished, the trap can be reopened by rebuilding the turgor pressure in the top layer of cells.4 Suction: Suction traps are found only in bladderworts, a type of aquatic plant, which have highly modified leaves shaped like

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little bladders (Figure 3).2 The plant uses the bladders to capture prey by pumping water out of them, which lowers the water pressure inside. When prey swim past the trap, it sets off trigger hairs that open a flap.

The low pressure sucks the prey in and the “door” to the outside quickly closes, trapping the prey inside.3 Lobster Pot: Named because of its similarity to traps used to catch lobsters, Figure 1: Nepenthes pervillei a type of lobster pot traps are pitcher plant. easy to enter but hard to exit because of their maze-like structure. Most prey can’t find their way out and are therefore trapped inside the plant. An example of this is found in Sarracenia psittacina. S. psittacina’s trap has a dark hole for prey to enter, and many translucent white patches. Once inside, the prey orient to the light patches, thinking it is a way out, but cannot find the actual exit (Figure 4).6 Pigeon: Similar to lobster pot traps, pigeon traps also are easy to enter. However, they employ a different mechanism of keeping prey trapped inside. Instead of obscuring the exit, pigeon traps have hairs that only allow the organism to move in one direction: further into the trap. S. psittacina, in addition to employing lobster pot techniques, also has a secondary pigeon trap in the neck of the trap (Figure 4).6 Digestion and Absorption There are numerous ways a plant can digest its prey once captured, depending on the type of trap and other traits of the plant. Pitcher plants work in a relatively straightforward manner: the insects fall into a pool of digestive enzymes and, once digested, the nutrients are absorbed by the leaf.7 Venus Fly Traps, once closed on prey, seal very tightly so that digestive enzymes can be secreted into the trap. Digestion takes about five to twelve days and the nutrients are absorbed directly into the leaf composing the trap. When it reopens, only the insect’s exoskeleton remains.8

Letters Drosera, or sundews, curl their leaves around the insect once it is stuck in the sticky mucus. By wrapping around the organism, many of the stalked glands are in contact with the prey. The glands release digestive enzymes and can also absorb nutrients along with the leaf surface. Some plants also have bacteria aiding in the digestive process.7 The Benefit of Carnivorism Carnivorism in plants is incredibly inefficient. The nutrients derived from the prey usually consist of nitrogen, phosphorous, and other nutrients that allow the plant to continue using photosynthesis to capture its energy. The plant is actually expending energy by doing this, especially because the modified leaves are less efficient at photosynthesis than the flat leaves of other plants.3 So what allowed this behavior to develop and continue to persist?

Most carnivorous plants grow in poor soil with low nitrogen and phosphorous content, like that found in bogs. However, bogs have plenty of water and sunlight. So for carnivorous plants, the nutrients derived from the prey are worth sacrificing more energy to obtain. Also, the abundance of sunlight ensures that the less photosynthetic efficient traps still capture enough energy to sustain the plant. This is certainly a trade off, but it’s one that been made multiple times in evolutionary history. In fact, carnivorism in plants has evolved independently at least six times, which would not occur if the strategy were not effective.3 Carnivorous plants break our normal definition of what a plant is capable of doing. They show that plants are not the boring, passive organisms we sometimes perceive them to be; they in fact represent dynamic systems that are well adapted to their environments in often elaborate ways. Carnivorous plants illustrate the amazing ways in which evolution can work to create intricate mechanisms, the result of which is the great diversity in species we see today.

References

1. Brittnacher, J. (n.d.). What Are Carnivorous Plants? Retrieved from http://www. carnivorousplants.org/cp/WhatAreCPs.php 2. (n.d.). Carnivorous Plants/Insectivorous Plants. Retrieved from http://botany.org/ Carnivorous_Plants/ 3. Zimmer, C. (2010, Mar). Carnivorous Plants. National Geographic. Retrieved from http://ngm.nationalgeographic.com/2010/03/carnivorous-plants/zimmer-text/1 4. Niels. (2009, May 12). The Trapping Mechanism of a Venus Flytrap. http://www. flytrapcare.com/trapping-mechanism-of-a-venus-flytrap.html 5. Volkov, A.G., Adesina, T., Markin, T.S., & Jovanov, E. (2008). Kinetics and Mechanism of Dionaea muscipula Trap Closing. Plant Physiology, 146(2). Retrieved from http://www.plantphysiol.org/content/146/2/694.full 6. Brittnacher, J. (n.d.). Carnivorous Plant Trapping Mechanisms. Retrieved from http:// www.carnivorousplants.org/cp/TrappingMechanisms.php 7. Brittnacher, J. (n.d.). Carnivorous Plant Digestion and Nutrient Assimilation. Retrieved from http://www.carnivorousplants.org/cp/Digestion.php 8. Matt. (2008, Apr 4). Background Information on Venus Flytraps. Retrieved from http://www.flytrapcare.com/venus-fly-trap-information.html Figure 1: http://upload.wikimedia.org/wikipedia/commons/e/e6/Nepenthes_ pervillei1.jpg Figure 2: http://www.sarracenia.com/photos/dionaea/dionamusci091.jpg Figure 3: http://www.scientificcomputing.com/sites/scientificcomputing.com/ files/legacyimages/Images/01_2012/Bladderwort_hm1.jpg Figure 4: http://www.carnivorousplants.org/cp/images/SpsittacinaInside.jpg

Figure 2 (top): A close up of the snap traps on the wellknown Venus flytrap, Dionaea muscipula.

Figure 3 (middle): The bladder trap of Utricularia gibba, a bladderwort.

Figure 4 (bottom): The trap of Sarracenia psittacina cut in half lengthwise to show the lobster pot and pigeon trap mechanisms.

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Letters

Advances in Kidney Transplantation Thomas Savage ‘15

Kidney transplantation faces both scientific and practical problems. Organs most often come from recently deceased individuals who have chosen to have their organs donated. Heart transplants, for instance, can only come from the deceased.

In kidney transplantation, however, a complete kidney can be transplanted from a living donor, as humans have two kidneys and need only one. While many novel strategies are being explored to improve organ donation, we focus here on the advances being made for those patients who are kidney transplant recipients.

The recipient’s immune system is the greatest obstacle to successful organ transplantation. Since the transplant recipient’s immune system recognizes the donated organ as foreign, it attacks the donated tissue—a process known as rejection. Recipients generally must be treated with drugs that suppress their immune system in order for the transplanted organ to function successfully.

It follows that a major goal of organ transplantation research is to teach the recipient’s immune system to recognize the donor’s cells as self, a phenomenon called tolerance, which would allow the discontinuation of immunosuppressive drugs.

To understand the techniques that have been developed to achieve tolerance, the mechanisms of rejection must be understood.

Lymphocytes (T cells and B cells) are the most powerful cells in the immune system. Most often, it is T cells that drive rejection. Each

T cell has a unique immune-trigger, known as an antigen, and the population of T cells as a whole recognizes nearly every antigen an individual might encounter, ranging from viruses to parasitic infections. In a healthy individual, however, T cells do not respond to self-antigen, meaning that a person’s immune system will not attack his or her own cells. T cells proliferate after recognizing their unique foreign antigen. One group of T cells, known as regulatory T cells or Tregs, stifle the proliferation of other T cells against the antigen they (the Tregs) recognize.

A kidney transplantation recipient’s T cells will recognize the donor organ as foreign and proliferate, eventually destroying the organ. Thus, to keep the transplanted organ, the recipient’s immune system must be suppressed. Although immunosuppressive drugs may be able to prevent rejection, they also suppress regular immune responses, making the patient susceptible to many simple infections and malignancies. Furthermore, in kidney transplantation, many of these drugs are toxic to the new kidney.

Research has focused on techniques to minimize or eliminate the use of immunosuppression, primarily by having the recipient’s immune system recognize the donor’s cells as self. One line of thought is to transplant a kidney and hematopoietic stem cells from the same donor; simply put, doctors would perform a bone marrow transplant in addition to a kidney transplant. Hematopoietic stem cells (HSCs) are precursors to blood cells, and must be harvested

Figures 1a (left),1b (right): Shown are diagrams of isolated stem cell transplants and the anatomy of a recipient of a kidney transplant.

The recipients in the studies discussed here received both kidney and stem cell transplants.

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Letters

Figure 2: Shown is the patient data from the two MGH studies discussed. (Data table adapted from reference 4). from the bone marrow. A group at Massachusetts General Hospital (MGH) has recently completed two clinical trials treating kidney failure with combined kidney and HSC transplants.1,2 Seven of the ten patients in the studies were successfully withdrawn from immunosuppression with long-term stable kidney function.1,2 Crucial to the success of the withdrawal of immunosuppression is that the recipient’s cells do not recognize the donor’s cells as foreign; in this situation, the recipient is “tolerant” to the donor.

In the study, the donor HSCs eventually developed into blood immune cells, repopulating the blood as donor cells.2 Based on previous experiments, the researchers thought that the presence of circulating blood donor HSCs would educate the recipient T cells to recognize donor cells as self.1 The presence of donor immune cells in the recipient’s blood (known as “chimerism”) can cause other complications. The most prominent is graft-versus-host disease (GVHD). Just as the recipient’s immune system recognizes the donor as foreign, the donor’s immune cells can recognize the recipient cells as foreign and attack them. This can be fatal for some patients.

Chimerism that only lasts a couple of weeks (transient chimerism) would reduce the risk of GVHD since, after a couple of weeks, no donor cells would exist to attack the recipient. The patients in the MGH studies had transient blood chimerism, yet the studies were still successful in withdrawal of immunosuppression, meaning the donor kidney was still present and active, but no

donor cells remained in the blood.1,2 Therefore, the mechanism of tolerance could not have been due to the mutual presence of donor and recipient cells, as no donor cells remained. Further investigation was needed to understand why the patients did not reject their kidneys in spite of the loss of chimerism.

To study how tolerance was induced, scientists used several in vitro assays, including a mixed leukocyte reaction (MLR), which detects the response of one group of lymphocytes against another group. Here, the proliferation, or lack thereof, of recipient blood T cells can be detected when they are exposed to pure donor cells (collected pre-transplant). In MLRs for the patients who were successfully withdrawn from immunosuppression, recipient cells failed to proliferate against donor cells, meaning the recipient blood T cells did not mount an immune response against the donor cells.2,3 If the recipient T cells recognized donor lymphocytes as self in vitro, they would fail to recognize the donor kidney as foreign, meaning the donor kidney could continue to function properly in the recipient. Against an unrelated third party, however, the recipient cells did indeed proliferate.3 The recipients were tolerant towards their donors, but their immune systems were otherwise competent.

How did the recipients become tolerant to the donor cells and kidney? One possibility is that Tregs suppressed the anti-donor response. To test this, MLRs without Tregs were performed.

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Letters in the Treg-depleted MLR should have been detected. Instead, the recipient cells failed to proliferate against the donor cells even without the presence of Tregs, meaning the recipient T cells specific to the donor were either non-functioning or eliminated.3 These possibilities are currently being investigated.

Interestingly, the kidney is also implicated in the mechanism of tolerance. The same drug protocol as developed for the combined transplantation of kidney and stem cells was performed for stem cell transplantation alone, yet when the chimerism was lost, the anti-donor response remained strong.3 In the combined kidney and stem cell transplant study, after the loss of chimerism, tolerance was maintained.3 Since the presence of the kidney was the only difference between the studies, it must play a role in the maintenance of tolerance.3 This role is currently being explored.

In summary, the infusion of donor stem cells results in the recipient immune system learning to tolerate donor cells, even well after the transplantation. The mechanism involves the loss of function or deletion of donor-specific recipient lymphocytes, and not a suppression of donor-specific response. Moreover, the kidney itself is implicated in the mechanism of tolerance.

In the clinical setting, the MGH protocol avoided GVHD, a potentially problematic result of the HSC transplant. Moreover, the recipients’ immune systems were competent in that, while failing to attack donor cells in vitro, they attacked unrelated thirdparty cells. Less desirably, the protocol was developed for living donors, and because of an extensive pre-transplant regimen, this protocol cannot be adapted for the more frequent deceased donor transplants, making its clinical application more limited.

A long-held goal of organ transplantation research has been to transplant without the need to have long-term immunosuppressive drugs. Recent developments have demonstrated that this goal is achievable, and, soon, transplant recipients may be able to live healthier lives without immunosuppression.

References 1. Kawai, T. et al. HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression. New England Journal of Medicine 358, 353-361 (2008).

2. LoCascio, S.A. et al. Mixed chimerism, lymphocyte recovery, and evidence for early donor-specific unresponsiveness in patients receiving combined kidney and bone marrow transplantation to induce tolerance. Transplantation 90, 1607-15 (2010).

3. Andreola, G. et al. Mechanisms of donor-specific tolerance in recipients of haploidentical combined bone marrow/kidney transplantation. Am J Transplant 11, 1236-47 (2011).

4. Kawai, T. et al. HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression. New England Journal of Medicine 368, 1850-1852 (2013).

Figure 1a: http://patienteducationcenter.org/wp-content/ themes/default/image.php?image=205426 Figure 1b: http://weill.cornell.edu/cms/health_library/images/ ei_2597.jpg

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Letters

Minicircles Minjee Kim ‘17

“Would you like to work with minicircles?”

In high school, one of the post-doctoral researchers asked me this question after I had volunteered in the lab for a little over a year.

The lab, part of Seattle Children’s Research Institute, researches ways to treat cancer, such as leukemia and neuroblastoma. To treat cancer, the scientists engineer receptors against the tumor-specific markers for human T cells, a type of human immune cell. The post-doc who offered me the project with minicircles worked on a way to control these receptors so that there was an ON/OFF switch for the engineered T cells.

In order to insert the engineered receptors and the switch to human T cells, the post-doc researcher was exploring a gene delivery method - minicircles.

Genetic Engineering Gene therapy is an experimental treatment involving insertion of a genetic material into the patient’s cells to fight a disease. Gene therapy has been used to alter the genetic mutations in sickle cell anemia and deliver cancer-targeting genes for cancer treatment (as in the lab I worked with). It can also be used to deliver genes as a form of vaccination or to deliver genes that promote healing of damaged tissues or cells.

In gene therapy, it is important that the inserted genetic material has a stable expression (translation of a protein over a period of weeks) and that it does not trigger an immune response

Figure 1: In a viral delivery system. The viral vector (vehicle to transfer genetic material) inserts the gene into the cell, integrating the gene into the cells’ chromosome.

from the host. Viral and non-viral gene delivery systems are the two most common methods used to deliver engineered genes to a target cell. Viral gene delivery systems introduce the engineered gene to the cell. The gene integrates to the cell’s genome and thus replicates as the cell replicates.

The viral gene delivery systems provide high expression of the engineered gene. However, viral vectors could lead to mutations in the patient’s genome, caused by insertion of new genetic material.i On the other hand, the use of non-viral gene delivery systems has been limited due to its toxicity. The most commonly used non-viral gene delivery system is bacterial plasmids. This creates problems because white blood cells can recognize bacterial motifs (recurring sequences) in a gene and turn off the gene’s expression.ii Additionally, both viral and non-viral gene delivery systems pose a risk of immune response.iii Because of the risk of immune response against traditional viral and non-viral vectors, gene therapy has been limited for clinical use. If the immune response of the vectors could be reduced however, gene therapy would be safer for clinical use.

Minicircles Minicircles (MC) are non-viral, plasmid-based gene delivery systems.iv Unlike standard bacterial backbone vectors commonly used, such as plasmids extracted from bacteria such as E. coli, MCs are devoid of bacterial backbone elements, such as the antibiotic resistance markers or the bacterial origin of replication. Because of this, MCs are less likely to cause immune responses in human cells.

MCs are generated by intramolecular recombination catalyzed by an enzyme called PhiC31.v Shown in Figure 2, the PhiC31 recombines Site A and Site B together so that the parental plasmid is split into two smaller plasmids, Plasmid A and Plasmid B. Because the gene of interest was placed in between Site A and Site B, at the end of the recombination, this gene is part of one of these smaller plasmids, Plasmid A. This Plasmid A containing the gene is the minicircle. Plasmid B, containing the bacterial components, such as the antibiotic resistance, is the bacterial backbone. In the recombination process, the two sites (Site A and Site B) are modified so that they are unrecognizable by PhiC31 and thus cannot recombine a second time. The bacterial backbone, or Plasmid B, will contain an endonuclease restriction enzyme site that will be cut by the restriction enzyme when added. When cut, the bacterial backbone will degrade.

It is also important to note that since the minicircle lacks an origin of replication, the minicircle cannot replicate.vi As time goes The Amherst Element, Vol 6, Issue 1. Fall 2013

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Letters sample Control mCherry only iRFP only GFP only iRFP + GFP mCherry + GFP iRFP + mCherry iRFP + mCherry + GFP

vector

concentration (1x) None None mCherry Minicircle 2ug iRFP Minicircle 2ug GFP Minicircle 2ug iRFP and GFP 1ug each Minicircles mCherry and GFP 1ug each Minicircles iRFP and mCherry 1ug each Minicircles All minicircles 0.65ug each

Table 1: To test whether multiple minicircles could be taken up by a cell (multiplexing), we tested with minicircles with different flourescent proteins.

Figure 2 (top): Simplified illustration of Minicircle production.

Figure 3 (bottom): Potential Use of Multiplexing Minicircles in Cancer Therapy. on, cells expressing the minicircle gene die or get outnumbered by the newly replicated cells. Therefore, the expression of minicircle is transient.

Multiplexing Minicircles Multiplexing minicircles is inserting multiple minicircles into one host cell. In the scope of our lab’s research, we would be inserting multiple receptors (targeting different tumor-specific antigens) onto each one of the T cells.

In order to see if multiplexing MCs would result in an expression of all of the genes in each of the MCs, I used three fluorescent proteins as my genes of interest: GFP, mCherry, and iRFP, which fluoresce green, red, and dark red respectively.

Different minicircles would express different fluorescent proteins.

I then put the minicircles into T cells. In order to see the effect of multiplexing, 8 samples were used with a control (Table 1).

The results were analyzed using flow cytometry. In flow cytometry, suspended cells pass through a separation chamber in a stream of single particles. These cells are hit with beams of laser light and produce fluorescent emissions, which vary in wavelength, depending upon their attached fluorescent markers.

This fluorescent emission creates voltage spikes that are amplified and plotted on a graph.

When analyzed, the T cells expressed either GFP, iRFP or mCherry depending on the combination of fluorescent protein

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(FP) expressing MC vectors. Multiplexing two MCs resulted in a less intense signal than using only one vector, and multiplexing three MCs resulted in a less intense signal than multiplexing two MCs. (Fig. 4, 5, 6). The expression of iRFP was the weakest, with 43.4% of the cells expressing iRFP compared to 55.8% of GFP and 61.3% of mCherry (Fig 4).

As more MCs were inserted into T cells, expression of each FP decreased. This could have been due to the decreased concentration of each MC for every additional MC. Significance of Minicircles Since minicircles are less likely to cause immunogenic responses in human host cells, they could be safer than the more traditional gene therapy methods that use bacterial backbone.

Furthermore, single MC insertion is highly effective and could yield a higher percentage of gene expressivity even when used in small volumes. Therefore, a smaller volume of engineered genes can be inserted to the cell compared to the traditional plasmid containing the bacterial components. Smaller volume would reduce the risk of an immune response from the patient. Viral vectors have been typically used to insert genes into the patients’ cells.

These cells would be reinserted in the patients for treatment. Using minicircles instead of viral vectors would yield higher expression of the therapeutic genes at lower risk to the patient.

Additionally, multiplexing minicircles may enhance gene therapy by broadening the number of expressed genes in a cell.

For example, in cancer therapy, multiplexing minicircles expressing unique antigen receptors can broaden the number of cancerous cell targets.

Further Work Needed The limitation of using minicircles for therapy is that their expression is transient. In my experiment, the expression of FPs lasted for only 7 days. Therefore, finding a method to allow the

Letters Figure 4 (top): Single Minicircle Expressions.

Figure 5 (middle): 1X Day 2 Multiplexing 2 Minicircles. The percentage shown on Q2 represents the percentage of cells that are positive for both FPs.

Figure 6 (bottom): 1X Day 2 Multiplexing 3 MCs. The dot plot sample was gated for cells that expressed iRFP. Of the 29.1% iRFP+ cells, 73.4% cells also expressed GFP and mCherry. minicircles to replicate would be needed in order for the minicircles to be an efficient gene delivery system in real-life clinical use.

A method to replicate the minicircle as the cell replicates is to insert a Scaffold/Matrix attachment region (S/MAR) into the gene of interest. For example, my previous gene of interest was just FP, but with S/Mar region, would change into S/MAR-FP. S/ MAR are regions of DNA that attach to the nucleus.viii When they are inserted, they move the minicircle to the nucleus so that the minicircle is replicated as the cell divides.ix References 1. Cavazzana-Calvo M., et al. (2000). Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 288: 669–672 doi: 10.1126.

2. Krieg AM. (2002). CpG motifs in bacterial DNA and their immune effects. Annual Review Immunology 20: 709-760 doi 10.1146.

3. Kobelt D, Schleef M, Schmeer M, Aumann J, Schlag PM, Walther W. (2013). Performance of high quality minicircle DNA for in vitro and in vivo gene transfer. Mol Biotechnology 53(1): 80-89 doi 10.1007.

4. Jia F., et al. (2010). A nonviral minicircle vector for deriving human iPs cells. Nature 7(3): 197-199 doi 10.1038.

5. Chen Z., He C., Ehrhardt A., Kay M. (2003). Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo. Molecular Therapy 8(3): 495-500.

6. Ronald J., et al. (2013). Development and Validation of NonIntegrative, Self-Limited, and Replicating Minicircles for Safe Reporter Gene Imaging of Cell-Based Therapies. PLos One 8(8): e73138.

7. Maniar L., et al. (2012). Minicircle DNA Vectors Achieve Sustained Expression Reflected by Active Chromatin and Transcriptional Level. Molecular Therapy 21(1): 131-138 doi 10.1038.

8. Evans K., Ott S., Hansen A., Koentges G., Wernisch L. (2007). A comparative study of S/MAR prediction tools. BMC Bioinformatics 8: 71 doi 10.1186/1471-2105-8-71.

9. Heng, Henry H. Q, et al. (2004). Chromatin loops are selectively anchored using scaffold/matrix-attachment regions. Journal of Cell Science. 117: 999-1008 doi: 10.1242

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Letters

Coca and its Effects Kevin Mei ‘16

When I went soul-searching in Bolivia over the summer, I found a curious habit there of chewing coca leaves. My first encounter with coca (and what would become a common sight) was watching my bus driver picking coca leaves out of a bag, ripping and spitting the stem out, and building up the ball of coca in his cheek, as he wound several hours through treacherously thin mountain roads, absent of rail guards. Throughout the Andean region, notably Bolivia, Colombia, and Peru, where coca grows best, it is a cash crop, and comes in many forms: tea, candy, and (at one café I visited) beer. Because it is a stimulant and a staple, people chew coca as Americans drink coffee. It is perhaps most famous for the alkaloid (basic compounds with nitrogen) it contains– cocaine, isolated from coca by acid-base extraction– and for its name in the Coca-Cola brand, which incidentally did have cocaine in its early drinks [1]. Now, coca is still incorporated into the famous soft drink, but in a de-cocainated form. Coca has a rich history culturally, religiously, economically, and politically and I encourage everyone to investigate these other aspects of coca.

Figure 1: Coca tea made by boiling coca leaves in hot water.

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Coca belongs to the family Erythroxylacea with the popular species being Erythroxylum coca. Though historically used by the ruling class of the Incan empire, it is now widely chewed by workers–long-distance drivers, miners–to withstand physical labor and the general population as a stimulant and herbal remedy.

Consuming coca leaves is believed to stave off hunger, increase stamina, and help withstand high altitudes. I have chewed coca myself for going on hikes and drank the tea when feeling sick.

Nutritional Value of Erythroxylum coca “Guard the leaves with much love and when you feel the sting of pain in your heart, hunger in your body and darkness in your mind take them to your mouth...”

-Coca legend [2]

Letters

Figure 2: The emphasis on this graph is in the center, comparing COCA AVERAGE to PLANT FOOD AVERAGE. Coca provides a valuable source of vitamins (B1, B2, C, E) and minerals (calcium, potassium, phosphorus) [3].

Chewing of coca leaves is called “acullico” and involves manually removing the stem or vein of the leaf. The leaf is masticated slowly and softly in the mouth so that the cell walls are ruptured. Gradually, as more leaves are taken, a bolus builds up in the mouth that is left to soak in saliva. Human saliva is alkaline and releases the nutrients and alkaloids in the coca. The bolus of coca is then spit out.

There has been contention that coca causes malnutrition because people who chew coca are likely to not eat from lack of hunger. This is not true; coca is drunk or chewed in supplement to meals. A Harvard study looked at the nutritional content of coca leaves (Fig. 1) [3]. The authors compared coca to 10 cereals, 10 plants, and 10 fruits. We see from the coca average and the plant food average that coca beats plants in all the categories except fat content. A problem with the study is that coca is not ingested directly but chewed or steeped for tea. A second problem is that coca is not taken at 100g, as used in the study. Miners that chew coca all day only use a maximum of 45g. The average person takes less than 10g [4]. Because coca is not “eaten” conventionally at any significant amounts, it does not provide substantial carbohydrates, fatty acids, or proteins.

Coca does provide a source of vitamins (B1, B2, C, E) and minerals (calcium, potassium, phosphorus) that consumers may not regularly encounter. In particular, experiments have shown that it provides calcium for pregnant, lactose-intolerant women and that coca helps the body absorb vitamin and nutrients [4].

Coca also stabilizes blood glucose levels in populations that are heavily dependent upon carbohydrates. Coca leaves might not provide the nutrients, but it helps alleviate nutritional deficiencies in populations that have limited food choices: rice, potatoes, beans [5].

Coca as an Anesthetic Coca contains four alkaloids–cocaine, norcocaine, ciscinamilcocaine, and trans-cinamilcocaine–of which cocaine is a potent anesthetic [6]. Cocaine is a vasoconstrictor and a nerve blocker. It works by diffusing into the mucous membrane and inhibiting the formation of action potentials in neurons. Its anesthetic properties appear to allow coca consumers to withstand temperatures and physical distress. Like nasal inhalation of cocaine, the oral chewing of coca also allows absorption of the alkaloid into the bloodstream where it interacts with the nervous system.

Chewing coca produces a numbing effect on the gums, tongue, and cheek where the coca is sequestered. While coca has been chewed since prehistoric times (evidence from mummies with bulges in their cheeks), in the sixteenth century, it was mixed with calcium carbonate to enhance its effects and increase absorption of the alkaloids [7]. Some chewed coca to alleviate toothaches. Perhaps it was from these effects on early consumers that suggested coca’s anesthetic properties.

Its development as an actual anesthetic came slowly but surely.

Pre-modern use of coca was to crush it and apply it to wounds.

Doctors believed it disinfected and helped heal wounds, though this is dubious. After cocaine was able to be isolated, experiments were done to test its efficacy.

Initial studies were somewhat haphazard [7]. One experiment showed that injecting cocaine solution into rats, guinea pigs, and frogs caused insensitivity. A physician Basil von Anrep injected cocaine solution into dogs, cats, rabbits, and pigeons, as well as himself (arm and tongue) and found that jabbing the treated region produced no sensations. The physician Sigmund Freud was an infamous user of cocaine and according to some sources, its first user. He tested cocaine’s ability to overcome morphine addiction The Amherst Element, Vol 6, Issue 1. Fall 2013

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Fig 3: Chewing leaves leads to little cocaine absorption over a longer period of time. [2] and recommended its use, while noting that it did produce an anesthetic effect. Cocaine became the first local anesthetic after the ophthalmologist Carl Koller first used it for a glaucoma patient operation; after, its use exploded. Inevitably, people also discovered the side effects and dangers of cocaine use: toxicity, addiction, and in cases of overdose, death. Many derivatives of cocaine have been synthesized for anesthetic use– novacaine, procaine, lidocaine– but all have their (minor compared to cocaine) drawbacks.

Coca’s Physiological Effects It should be noted that while coca leaves do contain cocaine, its content is between 0.25% and 0.77%, a small amount [4].

Cocaine itself is slowly and gradually absorbed into the body from coca chewing as opposed to the “high” people get from “snorting” crack cocaine. Perhaps the final point is that the coca plant itself is much more complex than the single alkaloid. Coca contains an array of minerals, oils, and pharmacological compounds that are not well characterized or understood.

As a mild anesthetic, coca is used to treat a variety of pains: toothaches, headaches, abdominal pain. Coca exerts a mild anesthetic effect that alleviates pain in the intestinal tract and at the systemic level. It’s also been used topically on wounds and sores. Because it is a vasoconstrictor, coca is sometimes used to relieve nosebleeds. Its breadth of use ranges from broken bones, childbirth, and malaria to being an aphrodisiac and a drug for longevity. Most of these uses are scientifically untested but historically and culturally practiced, as most herbal remedies are.

Coca dilates the bronchioles and allows greater absorption of oxygen, but has not been found to affect the lung capacity [2]. In this way, coca is often used to treat altitude sickness and to help people adapt to Andean mountain conditions. It regulates insulin levels and improves the utilization of energy. Glucose levels drop in non-consumers after 2 hours of activity, but remain constant in coca consumers.

Coca is an innocuous and broadly beneficial plant, usually chewed or taken as tea. Produced and widely consumed throughout the Andean region, coca has helped people tolerate physical labor, adapt to high altitudes, and cure pains through its range of physiological effects such as stabilizing blood glucose levels, correcting the imbalances of a high-carbohydrate diet, and improving respiration.

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References 1. May, Clifford D. “How Coca-Cola Obtains Its Coca.” The New York Times. The New York Times, 01 July 1988. Web. 26 Oct. 2013.

2. Hurtado, Jorge G., Dr., and Sdenka B. Silva. The Coca Museum: English Language Guide. Trans. Jon C. Roglofs. N.p.: n.p., n.d. Print.

3. Duke JA, Aulik D, Plowman T - 1975 Nutritional value of coca.

Botanical Museum Leaflets Harvard University 1975; 24(6): 113-8 4. Henman, Anthony, and Plen Metaal. “Coca Myths.” Ed. Martin Jelsma and Amira Armenta. Drugs & Conflict 17 (2009): n. pag. Web. 5. Bolton, Ralph. “Andean Coca Chewing: A Metabolic Perspective.” American Anthropologist 78.3 (1976): 630-34. JSTOR. Web. 6. Hurtado, Gumucio Jorge. “2: The Coca Leaves: Scientific Aspects.” Cocaine, the Legend: About Coca and Cocaine. La Paz, Bolivia: Accion Andina, ICORI, 1995. N. pag. Print.

7. Calatayud, Jesus, and Angel Gonzalez. “History of the Development and Evolution of Local Anesthesia Since the Coca Leaf.” Anesthesiology 98.6 (2003): 1503-508. Print.

Letters

Fluorescence, Hearing, and Zebrafish Azka Javaid ‘17

Zebrafish and Hearing Ninety percent of hearing disorders in humans are caused by loss of hair cells in the inner ear due to acoustic (sound) or ototoxic (chemical) damage. When these human hair cells in the inner ear are lost, they don’t regenerate. In comparison, zebrafish hair cells in the lateral line do regenerate after damage.2 It is useful to understand the mechanism of zebrafish hair cell to develop potential therapeutic interventions for human hearing disorders.

Zebrafish is an ideal model organism because it undergoes rapid reproduction, allowing for more trials and experiments. Both humans and zebrafish are vertebrates and possess auditory hair cells. Sound causes the hair cells to deflect and the subsequent vibrations are converted into electrical signals in the nervous system. Unlike human auditory hairs, located in the inner ear, zebrafish hair cells are superficial and are a component of the posterior lateral line, a system of seven to nine sensory cells, called neuromasts (Figures 1A & 1B), on the lateral sides of the zebrafish.

In zebrafish, hair cells are deflected by water waves, allowing the zebrafish to detect nearby prey and predators.

Zebrafish hair cells regenerate in steps. First, mantle cells, which surround the neuromasts, produce support cells, which produce progenitor cells, which ultimately give rise to hair cells.1 Interneuromast cells connect the neuromasts and express the same genetic marker– ET20– as mantle cells. This marker is a DNA sequence believed to play a role in hair cell regeneration, suggesting that interneuromast cells function in the regeneration process.

Methods of Experimentation Last summer at the Hudspeth Lab in Rockefeller University, I researched interneuromast regeneration following laser damage in zebrafish. We used lasers to remove interneuromast cells in the zebrafish in a process called ablation. Zebrafish hair, mantle and interneuromast cells were fluorescently labeled by the lab in order to visualize those structures. Green fluorescent protein, GFP, was used to label mantle and interneuromast cells while a red fluorescent protein, mCherry, was used to label hair cells (Figures 2A-E). Zebrafish were anesthetized and mounted in agarose, which allowed the fish to remain in a fixed orientation during the laser microscopy and imaging process.

Zebrafish were examined in sets of three on a dish, where one was a control. We used a laser under the confocal microscope to ablate the interneuromast cells of the first fish on the right side of a neuromast and the interneuromast cells of the second fish on the left side of the neuromast (See Figures 3A & 3B (right ablation) and figure 3C & 3D (left ablation)). The

Figure 1A: Zebrafish hair cell. Adapted from Ghysen and Dambly-Chaudiere, Current Opinion in Neurobiology, 2004 1B: View of superficial neuromasts (on the surface) from Jürgen Berger (Max Planck Institute for Developmetal Biology, Tübingen) 1C: (bottom) A schematic cross-section of an interneuromast illustrates the pattern of hair cell regeneration where mantle cells give rise to support cells which then produce hair cell-progenitor cells. Hair cell progenitor cells produce hair cells (Steiner). interneuromast cells were then hit with the laser for 30 seconds and the ablated region was verified by the loss of green fluorescence.

Following ablations, the fish were allowed to rest for 24 hours and then were imaged on a spinning disk microscope for 16 hours to produce a time lapse movie which visualized interneuromast cell regeneration.

Zebrafish hair cell regeneration Following ablations, extension and retraction of threadlike filaments were seen in the ablated region, but fully regenerated interneuromast cells were not observed. Cell division in the mantle cells was also observed, which may be part of the normal fish development. Alternatively, it is interesting to note that this cell division may be trying to replace the ablated interneuromast cells.3

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Letters Figures 2A-G: (from top to bottom) A shows image of fish without the fluorescence.

In B, red fluorescence is used to label mantle and interneuromast cells.

C utilizes green fluorescence for the same purpose while D and E contain merged red and green fluorescence allowing for better visualization of mantle and interneuromast cells.

Panel F shows a neuromast before ablation. The hair cells (labeled green) are present within the ring –like structure (mantle cells).

Interneuromast cells are string-like structures on either side of the neuromast.

Panel G depicts the same neuromast after interneuromast ablation on either side.

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Letters

Figure 3A: (top left) Image of interneuromast cells following right-side ablation.

Figure 3B: (top right)Image of right-side inteuromast cells at 800 minutes. Image shows thread-like extension of interneuromast cells.

Figure 3C: (bottom left)Image of interneuromast cells following left-side ablation.

Figure 3D: (bottom right) Image of interneuromast cells at 800 minutes. Retraction can be seen in comparison to graphic C. Future Implications: A limitation of the study was that full interneuromast cell regeneration was not observed. Zebrafish were not able to survive beyond 16 hours under the microscope and we don’t know if interneuromast cells would have fully regenerated if they could survive longer. Bleaching (loss of fluorescence) was another reason why fully regenerated interneuromast cells might not have been observed.4 Bleaching signifies that even if some interneuromast cells were regenerating, they could not be seen due to the loss of green fluorescence.

It would be interesting to follow up on the work and see what genes are involved in interneuromast cell regeneration and how scientists can use activation and suppression of those genes to affect hair cell regeneration in zebrafish. Further research can possibly lead to identification of the genes, if any, which might be involved in hair cell regeneration in the human ear. This could lead to new therapeutic applications where human hair cells in the ear can be regenerated after damage, leading to decreased hearing related complications.

References 1. Ghysen, A., & Chaudiere, C. (2007). The lateral line microcosmos.

Genes and Development, 21, 2118-2130. Retrieved July 10, 2012, from http://genesdev.cshlp.org/content/21/17/2118.full#cited-by 2. Harris, J., Cheng, A., Cunningham, L., MacDonald, G., Raible, D., &Rubel, E. (2003). Neomycin-Induced Hair Cell Death and Rapid Regeneration in the Lateral Line of Zebrafish (Daniorerio).

Journal of the Association for Research in Otolaryngology, 04, 219-234.

Retrieved July 8, 2012, from http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3202713/?tool=pubmed 3. Jones, Jay E., and Jeffrey T. Corwin. “Regeneration of Sensory Hair Cells after Laser Ablation in the Lateral Line System: Hair Cell Lineage and Macrophage Behavior Revealed by Time-Lapse Video Microscopy.” The Journal of Neuroscience 16(2) (1996): 649-62.

Web. 10 Aug. 2012. http://www.jneurosci.org/content/16/2/649. full.pdf.

4. Nishikagi, Takuya, Chris D. Wood, KogikuShiba, Shoji A. Baba, and Alberto Darszon. “Stroboscopic Illumination Using Light-emitting Diodes Reduces Phototoxicity in Fluorescence Cell Imaging.” BioTechniques 41 (n.d.): 191-97. Web. 13 Aug. 2012. http://www.biotechniques.com/multimedia/archive/00002/ BTN_A_000112220_O_2306a.pdf.

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Interview

Interview with Professor William A. Loinaz Ji Hoon Lee ‘16 This interview was conducted in the Spring of 2013.

Professor William Loinaz is the Professor of Physics and the Chair of Health Professions Committee at Amherst College. Aside from being a physics major, I decided to interview Prof. Loinaz, because I thought the interview would be of interest to both aspiring physicists and students on the pre-health track.

JHL – Ji Hoon Lee WL – Professor William Loinaz JHL: For the audience that may not be familiar with theoretical physics, what do theoretical physicists do?

WL: Theoretical physicists ask questions about the natural world and try to answer them based on fundamental principles of physics. While other scientists try to answer these questions by gathering data, performing experiments, and looking at the results of those experiments, theoretical physicists perform mathematical and thought-experiments to answer these fundamental questions.

We don’t perform experiments of the traditional kind in the lab, but we perform numerical or thought-experiments. A big part of my research involves looking at data from other experiments and interpreting them. In physics, there is somewhat of a gulf between the doing of the experiments and comparing the experiments to underlying theories.

JHL: So while experimentalists look at the results from their experiments to draw conclusions, the theorists do the reverse— draw conclusions with their theory and leave the experimentalists to confirm them!

WL: It goes both ways—it’s never clean and it’s always risky to put priorities on one over another.

I’ve worked as an experimental physicist, an engineer, a theoretical physicist, and a bit as a mathematician myself, but the delineations are not sharp. Sometimes theorists can produce ideas and make predictions that experimentalists can test, and other times experimentalists come up with results that theorists can interpret.

JHL: Why did you choose to pursue physics as a career?

WL: I actually don’t know if I ever did.

As an undergraduate, I decided to be a mechanical engineer, but I took most of the courses required for a math and physics major. I applied to many graduate programs, but I wasn’t sure what I wanted to do yet. I saw that one of the schools I applied for— University of Michigan—had agreed to provide funding and I decided that I

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Interview could spend a year there. It happened to be physics! Once I got there, I said to myself, “One thing I don’t want to do is theoretical particle physics.” [Laughter] There were a lot of unhappy people and infighting going on at the time.

JHL: [Laughter] That’s funny, because you actually ended up doing theoretical particle physics!

WL: Exactly! So I worked in an experimental atomic physics group for a while, making high-intensity positron and anti-matter sources that are used in the nuclear reactor, where I did a lot of hot and wet electrochemistry. At the same time, I was taking math graduate courses as part of my attempt to figure out what to do. Fortunately, I happened to get a fellowship that gave me the flexibility to do research in what I wanted to, so I studied condensed matter for a year, a subject on which I was also taking a class. From that experience, I learned some theory tools that I would use later in doing theoretical particle physics, when a spot opened up in the theoretical particle physics program. Despite what I had said before, that’s where I ended up [Laughter]. So I did a post-doctoral fellowship at Pittsburgh and Virginia Tech, then came here.

JHL: So what are your current research interests?

WL: The nice thing about theoretical physics is that you can be entirely promiscuous about your research interests, because you don’t have to sink a lot of money into buying apparatus. I have a few topics that are bread and butter work for me, but I often pick up others I am interested in, as they occur to me. From my last count, I had about a hundred-and-thirty projects that I was interested in. Much of the bread and butter work I do is called highenergy phenomenology. I am interested in understanding what the world is made of and how it works at the shortest-distance scales and highest-energy scales, where we have a good reason to think that they are the simplest. One of the things I do is look at the results from different kinds of experiments and try to compare them to different kinds of theories about small constituents and their interactions to see if they are consistent with each other.

To do this, I look at all kinds of experiments—data from Large Hadron Collider (LHC), etc.—to understand the nuts and bolts of the theoretical calculations, so I can make comparisons between the two. I’ve worked in different fields from within, like neutrino physics and the Higgs boson. Because I also have interests in experiments, I have also been working with some experimenters from MIT to suggest new kinds of experiments with neutrinos.

We recently made a big proposal to turn the Fermi Lab collider, which was, up until a few years ago, the most powerful particle accelerator in the world, into a high-energy neutrino machine. I also do computer simulations on simple quantum field theory.

These are meant less to be about making predictions about the world, but more about understanding the mathematical tools that are used in the field. I do calculations in quantum field theory that are addressable by approaching the problem in entirely different ways, using computer simulations to turn it into a statistical mechanics problem. Moreover, I find other projects to do here and there, such as quantum mechanics, biophysics, engineering, control theory, and robotics. What’s amazing is that it doesn’t cost

me anything except time and paper to do all this.

JHL: Going back to talking about your academic career, why did you choose Amherst and how do you like being a professor here?

WL: When I had started applying for jobs, there was a huge job crunch in academic physics, and I, like all of my peers, applied to many institutions. I saw that Amherst College had advertised a job in theoretical particle physics, and when I came, I was impressed at the research that was done here. I had done some work in experimental atomic physics—I understood what Professor Hall and Professor Hunter were doing, and I was pleasantly surprised that such work can be done at a liberal arts college.

JHL: What year was that, and how did you find the students?

WL: I came here in July of 2000, so I must have been interviewing earlier that year. When I met the students, I was very impressed.

They were really engaged in their work and sophisticated, and I thought they were working at the level of master’s students at Michigan, where I went to graduate school. So it turned out the students here were extraordinary, and they are all now faculty members in physics in various places. I was impressed at the resources that the college brought to both the research and teaching enterprise, and ended up staying here.

JHL: You’re teaching an introductory physics class—Physics 117—this semester (Spring 2012). Many students on the premedical track in your class would be curious to know, why do you think it’s important to learn physics as a student entering medicine?

WL: You know, it’s an interesting question with not just one crisp answer. For one, physics is on the MCAT—medical schools require two semesters of college physics, which is as much as they require biology. It is also true that physics encourages the drive toward finding simple, but effective models in many fields, including medicine. The goal of seeing similar structures in complicated phenomena, such as making quantitative models that make predictions, turns out to be useful almost everywhere. The power of this has been reflected in the migration of physicists into fields like biology, medicine, finance, and even the social sciences.

The technology that leads to many of the modern advances in medicine is the direct consequence of applications of ideas from physics. Magnetic resonance, CAT scans, proton therapy for cancers, use of nanoparticles for drug delivery, and, for that matter, the lab-on-a-chip technology—one just goes on and on to list the manifestations of usually simple physics applied cleverly to medicine. This technology has transformed the way that medicine has been done, and in order for you to understand the technology, you need to understand the physics.

JHL: Thank you for the interview, Professor Loinaz!

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