Volume VI Issue I FALL 2020

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Journal of Undergraduate Science & Technology

JUST VOL VI // ISSUE I // FALL 2020

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Journal of Undergraduate Science & Technology

UW-Madison's only undergraduate STEM research & communication journal

is RECRUITING for Spring 2021! editors | staff writers | designers and accepting submissions for: research reports | editorials | photographs

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LETTER FROM THE EDITOR-IN-CHIEF Dear Reader, I am elated to present to you with Volume VI, Issue I of the Journal of Undergraduate Science and Technology (JUST). JUST is truly a campus wide effort and a celebration of not only the extraordinary research that takes place on this campus, but the work conducted by undergraduates specifically. I would like to extend my sincerest thanks to the undergraduate researchers who submitted their work along with the faculty and staff who supported them. I would also like to express my gratitude for the JUST staff that have chosen to make JUST a part of their undergraduate experience and worked diligently to bring you this publication. Additionally, without the generous support of the Wisconsin Institute for Discovery, the Holtz Center for Science and Technology Studies, the College of Agriculture and Life Sciences, and Associated Students of Madison, the publication of this journal would not have been possible.

JUST’s mission has always been to support undergraduate researchers and make science accessible to broader audiences. At UW-Madison, we have been uniquely able to provide the opportunity for undergraduates to publish their work in a peer-reviewed journal and give students a glimpse into the publication process of an academic journal. On the other hand, our staff gain exceptional skills and experience the publication process from the perspective of a producer in a scholarly journal. We believe that these experiences are an invaluable supplement to a traditional undergraduate education, especially for those students who wish to continue research.

As for the second part of our mission, I believe that scientific literacy is more important than ever in today’s advancing society. STEM topics have immersed themselves in all aspects of daily life, and all of our lives can only be enriched by a solid understanding of scientific thought. Effective communication of research and science is key to this. We are honored to be a small part in a much larger effort to make research and scientific achievement more accessible to non-expert communities beyond academia.

In many ways, the space we occupy on campus mirrors the tenets of the Wisconsin Idea: that the influence of the university should better people’s lives outside of the classroom and across the state. We believe that by helping to train the next generation of researchers and assisting in the dissemination of scientific knowledge, JUST is helping to realize and advance the Wisconsin Idea.

JUST has brought me incredible opportunities to work with and support talented peers. It has truly been an honor to be a part of this organization and continue to forward its mission.

In this issue of JUST, you will find a wide range of scientific disciplines represented both by our peer reviewed reports and our shorter editorials as well as the visual pleasure of scientific imagery.

Please join us in making it a tradition to recognize the incredible research and thoughtful written pieces presented by UW-Madison undergraduates, and in our larger pursuit to support science literacy.

Sincerely,

www.justjournal.org | contact@justjournal.org Haley Dagenais JUST Editor-in-Chief JUST VOL VI // ISSUE I // FALL 2020

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TABLE OF CONTENTS

SPONSORS & PARTNERS

EDITORIALS

EDITOR-IN-CHIEF Haley Dagenais MANAGING EDITORS Aadhishre Kasat

We would like to sincerely thank the Integrated Studies in Science, Engineering, and Society Undergraduate Certificate Program [ISSuES] at UW-Madison; The College of Agriculture and Life Sciences [CALS]; The Wisconsin Institute for Discovery; the Associated Students of Madison (ASM) and Wisconsin Alumni Research Foundation for financially supporting the production of JUST’s Spring 2020 issue. Thank you!

Is Your Morning Coffee Harming You?...................6 Sarah Kamal

Sewage Surveillance to Detect Covid-19: A College Test You Dont Want to Pass..........8 Mahak Kathpalia

Successful Global Strategies Found to Handle the Covid Pandemic........12

DIRECTOR OF FINANCE Revati Garg

Anna Feldman

DIRECTOR OF MARKETING Jenny Lee

The Evolutionary Battle Between Bacteria, Antibiotics and Humans.....15 Carter Wood

DIRECTOR OF DESIGN Ashley Harris

The Importance of Interupting Bacterial Connversation.....20 Michael Kuehne

WEBMASTER Eddie Estevez

Vaccine Development: A Comprehensive Review for the Covid Age.....24 MARKETING ASSISTANT Hannah Landsly

Lydia Larsen

EDITORS OF CONTENT Catherine Nguyen Noah Jacobs Jaitri Joshi Joshua Lei Samantha Bebel STAFF WRITERS Aislen Kelly, Head Staff Writer Anna Feldman Parabhjot Singh Myra Mohammad Carter Wood Lydia Larsen Mahak Kathpalia Sarah Kama

PIXELS Ashley Harris...........................................................................18-19

REPORTS The Journal of Undergraduate Science and Technology (JUST) is an interdisciplinary journal for the publication and dissemination of undergraduate research conducted at the University of Wisconsin-Madison. Encompassing all areas of research in science and technology, JUST aims to provide an open-access platform for undergraduates to share their research with the university and the Madison community at large.

Discoveries in the Field of Brain Network Analysis ......22 Justin Magnus

PERSPECTIVES Pandemics, Politics and People......................................................................46 Myra Mohammad

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SCIENCE + SOCIETY: How to be creative and effective in a rapidly changing environment

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J ditions such as diabetes and heart disease. Aside from that, high blood sugar levels cause the body to develop an insensitivity to insulin, a hormone that allows the sugar that enters the bloodstream to be stored as fuel. An insensitivity to insulin can weaken the cells’ ability to utilize carbohydrates for energy. This deficiency in energy leaves individuals feeling hungrier and eating more (MitoQ). Knowledge of these health implications may affect a person’s decision to immediately turn to coffee after a night of restricted sleep.

HEALTH

Is Your Morning Coffee Harming You?

By Sarah Kamal

"Adult’s morning coffee ‘remedy’ may be increasing their alertness and concentration after a bad night’s sleep, but it can come at the cost of impairing the body’s ability to maintain healthy blood sugar levels. "

EDITORIAL

Adults experience nights of restricted sleep for a number of reasons. Sleep loss can originate from anything that comes with being a grown-up: stress, caring for children, busy work schedules and more. Fortunately,

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American Academy of Sleep Medicine. (2016, June 13).

Caffeine has little to no benefit after 3 nights of sleep restriction: New study shows caffeine is not sufficient to prevent performance decline long term. ScienceDaily.

Retrieved October 7, 2020 from www.sciencedaily.com/ releases/2016/06/160613130813.htm MitoQ. (n.d.). Why Is It Important To Have Balanced Blood Sugar Levels? [Retrieved October 12, 2020], from https://www.mitoq.com/blog/blog/important-balanced-blood-sugar-levels University of Bath. (2020, October 2). Drink coffee after breakfast, not before, for better metabolic control. ScienceDaily. Retrieved October 7, 2020 from www.sciencedaily.com/releases/2020/10/201002091053. htm Van Someren, E. (2010). Doing with less sleep remains a dream. Proceedings of the National Academy of Sciences of the United States of America, 107(37), 1600316004. Retrieved October 8, 2020, from http:// www.jstor.org/stable/20779603

In order to get the most out of their morning coffee, adults should develop new habits to overcome tiredness. First of all, the recommended eight hours of sleep should not be taken as a suggestion. Caffeine will not reverse all the effects of habitual sleep deprivation.

Moreover, eating breakfast before drinking coffee after a night of restricted sleep will prevent a negative blood sugar response to breakfast. This way, adults maximize the benefits of drinking coffee without potentially impairing their blood sugar control.

one night of restricted sleep is not too detrimental on the body’s metabolism. However, a cup of coffee before breakfast after a night of restricted sleep increases the blood glucose response to breakfast by 50% (University of Bath, 2020). Adult’s morning coffee ‘remedy’ may be increasing their alertness and concentration after a bad night’s sleep, but it can come at the cost of impairing the body’s ability to maintain healthy blood sugar levels.

EDITORIAL

It is no surprise that the best way to avoid tiredness is to get a good night’s rest. Rather than receive the recommended eight hours of sleep, however, many adults will instead resort to drinking coffee in the morning to combat tiredness. Unfortunately, this morning coffee ritual could be causing more harm than good.

Sleep deprivation can easily become a habit among adults — and it will not become easier to do more with less sleep. Regardless of how ‘accustomed’ people feel to being sleep deprived, the homeostatic set point will not reset with habitual lack of sleep (Van Someren, 2010). In other words, adults that regularly receive less than eight hours of sleep will never be able to adapt to less sleep over time. Instead, they will continue to suffer the numerous effects of sleep deprivation. Habitual lack of sufficient sleep reveals another problem with adult’s reliance on their morning coffee. Drinking coffee does not show sufficient effects in increasing alertness and performance after three days of restricted sleep (five hours of sleep or less) (American Academy of Sleep Medicine, 2016). This essentially defeats the purpose of the caffeine being consumed. After three days of insufficient sleep, individuals will not benefit from the same dose of caffeine. Once caffeine inevitably becomes futile, there is only one viable solution: sleeping more.

References

Keeping blood sugar levels within a safe range is what prevents individuals from long-term health conJUST VOL VI // ISSUE I // FALL 2020 7

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J mote instruction for two weeks. Many universities on the east coast, like New York University and West Virginia University, have also been slowly getting rid of the idea of in-person classes and suspending students for violating COVID-19 norms and conducting large gatherings and fraternity parties (Nierenberg & Pasick, 2020).

“The third wave is going to be these kids,” said Dr. George Rutherford, an epidemiologist at the University of California, San Francisco, who advises universities and other major institutions about the coronavirus (Richtel, 2020).

COVID-19

Prevalent Means of Testing and Their Limitations.

Sewage Surveillance to Detect COVID-19: A College Test You Dont Want to Pass

By Mahak Kathpalia

As the world battles the COVID-19 outbreak, most colleges across the United States have been struggling to resume operations and deliver a holistic on-campus college experience beginning this fall.

This decision has raised several grave logistical concerns ranging from the mode of academic instruction to on-campus housing because of all the associated health risks that need to be considered. A majority of schools had prepared for a hybrid reopening; buses and lecture halls were now being replaced with Zoom meetings, and desks spaced six feet apart. There have 8 JUST VOL VI // ISSUE I // FALL 2020

been multiple consequences on our lifestyle and policy encompassing masking requirements, social distancing, contact tracing, and more.

However, a prominent obstacle that still persists in this path towards recommencement is the plausible asymptomatic or pre-symptomatic spread of the virus in residence halls and dining areas leading to spikes in the number of infections. In early September, UW–Madison itself had observed staggering trends in the positive test rates, which resulted in quarantining two dorms (Sellery and Witte) and shifting to all-re-

History of Environmental Surveillance Programs

Although the technology has garnered a lot of national traction recently, the core scientific idea behind the same has been around since quite some time.

Virologists began to try using wastewater to identify enteroviruses (a group of viruses that cause mild illnesses) back in 1940s. Back then, they made use of cell cultures, but this was replaced by advanced molecular biology techniques in the 1990s when experts tried to detect pathogens that didn’t grow in cell cultures or grew with great difficulty. (Metcalf et al., 1995). The technique has also been implemented to monitor epidemics earlier.

According to the Centers of Disease Control and Prevention, the poliovirus had been eradicated from most of the world by 2008. However, when ongoing transmissions were tracked in countries like Israel without evident symptoms like acute flaccid paralysis, samples from the wastewater trunk lines were collected weekly and sent back to the country’s Central Virology Laboratory.

Epidemiologists than correlated “the relative levels of poliovirus, the coverage of the vaccination campaigns, and the differences in transmission between the wild virus and the attenuated vaccine virus” (Eisenberg et al., 2018) to come up with a statistical algorithm to control the propagation of the infection across borders.

"COVID-19 is a new disease, so a lot of questions yet remain unanswered."

The Science Behind Sewage Surveillance

The concept seems very fascinating, but is pretty easy to understand. Infected individuals excrete feces that contain the pathogen or fragments of its genes.

The stool then gets flushed down the toilet and ends up in a community’s treatment plant or sewage system.

The collected wastewater sample is concentrated to a given degree, so that it can be scanned for some RNA (Ribonucleic acid — an important macromolecule that performs biological functions in retroviruses like the coronaviruses). The RNA is too tiny to be physically isolated, so usually some electrostatic interactions are used which involve “getting the RNA to stick to something like a filter, or using other chemicals to get it to clump together” (Bibby, 2020). Next, researchers use molecular methods and nucleic acid targets suggested

by CDC to distinguish SARS-CoV-2 genetic markers in the samples before and after the wastewater treatment (Brandt, 2020).

The University of Arizona WEST Center uses a facility co-located with the Pima County Wastewater

EDITORIAL

EDITORIAL

"There have been multiple consequences on our lifestyle and policy encompassing masking requirements, social distancing, contact tracing, and more"

As ensuring compliance to regulatory regulations becomes grueling, an effective back-up plan to deal with the repercussions of a breach in rules needs to be developed. For this, efficient and brisk testing is critical.

Typically, the most common methods have been the nasal swab test and the antibody test. The former involves a six-inch long swab inserted into the cavity between the nose and the mouth and the specimen being sent to the lab to detect specific genes for the SARS-CoV-2 virus that causes COVID-19.

While the latter looks for the body’s immune response to the virus by recognizing antibodies in the patient’s blood sample. Both these tests have been significantly useful, but come at an expense of time, effort, and valuable means at a large-scale.

“Shortages of swabs and reagents for collection kits were among the several roadblocks that stymied public health agencies’ ability to perform widespread testing in recent weeks, according to David Harris, who directs the biorepository at the University of Arizona” (Daley, 2020). Administrative and computer systems need to be installed by labs that only conducted research to collect patient information and send it back to healthcare providers (Campbell & Epstein, 2020).

These tests take a few days to process, and past experiences have shown that the speed of testing is outrun by the speed by which the rate of infections is inflating (Vuong, 2020). Therefore, testing all students individually during regular intervals can be time-consuming and tedious. Further, it is turning out to be uneconomical and unsatisfactory in tracking the expanding sweep of the virus across university campuses.

Researchers at University of Arizona Water and Energy Sustainable Technology Center (WEST) along with a few other universities have now chosen to take up a unique approach to solve this dilemma — sewage surveillance. The novel method does not call for health insurance plans, nasal swabs, or finger prick sets. It only

requires you to defecate!

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J Treatment Plant, which already has crucial experience in environmental surveillance programs.

"We have tested for hepatitis A, enteroviruses and noroviruses. We have approximately 15 different viruses that we regularly test for in sewage and recycled waters for reuse applications," said Walter Betancourt, a microbiologist with expertise in environmental virology and assistant research professor in the Department of Environmental Science of the university (Brandt, 2020).

COVID-19 is a new disease, so a lot of questions yet remain unanswered. It is unclear as to what amount of the virus is secreted by each individual, which is why collected data cannot be simply extrapolated to predict the number of positive cases on campus or in a particular dorm (Bibby, 2020). Hence, the most integral application of this system continues to be direct surveillance.

However, we can forecast positive and negative shifts in the numbers to evaluate the performance of any given preventative measure being executed by the authorities and recommend necessary institutional modifications.

Why Is It Useful?

EDITORIAL

National and International Expansion of the Technology

The technology has extended to numerous universities like University of California, San Diego (UCSD), Syracuse University and Rochester Institute of Technology (RIT) throughout the nation (Richtel,

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Looking ahead: Challenges and Future Scope

While research and evolving innovations aim at making our lives more convenient, they pose unprecedented challenges. Environmental surveillance programs are no different. Despite the apparent benefits, the intervention’s privacy implications remain debatable. Some students who have been subjected to the procedure have felt somewhat disconcerted. Ryan Schmutz, a student of Utah State University who tested negative after the sewage from his dorm indicated the presence of the virus, was in quarantine for four days and did not miss out on much academically. Nevertheless, he expressed his apprehension to the entire process in an interview with Denver Post.

“It felt like we were kind of out of the loop on everything. It’s definitely hard to process,” he said. He went on to mention that he wasn’t even aware about the testing initially (Whitehurst, 2020).

Experts continue to be in the favor of the same and they believe that the students should do so too.

Ultimately, an inability to contain a massive outbreak on campus would directly impede the possibility of moving forward with any in-person activities and restricting the term to the virtual classroom. There still exists a grey area with regards to what extent analyzing students’ feces and body fluids regularly is ethical and does not pose a threat to their civic liberties.

Although surveillance programs have been conducted successfully in the past, a lot of science revolving around COVID-19 is unsettled and subject to error. Earlier research suggests that SARS-CoV and MERS-CoV can survive in excreted wastes in viable environmental conditions. SARS-CoV RNA found in two Beijing hospitals treating patients with SARS was observed to remain infectious for 14 days at 4°C. Although direct droplet infection remains the primary route of viral infection, such data unleashes speculation about the possibility of fecal-oral transmission (Yeo et al., 2020). If so, sincere efforts need to be initiated to assure the safety of all the people engaged in this practice including wastewater workers. As in the case of clinical diagnosis tools, issues affiliated with inaccuracies prevail. Procuring composite samples of wastewater and the fact that not all infected individuals will shed bits of the viral genome form two key causes of scrutiny. One infected individual could be excreting

100 copies of the coronavirus genome per gram of the feces, while another could be shedding 100 million copies per gram of feces. The margin is very wide and this can result in a false sense of progress in fighting the pandemic in discrete areas on campus (Bibby, 2020).

Around different corners of the globe, professionals are trying their best to catalyze the pace with which research is striving ahead so that we have definitive and conclusive answers to all the reasonable objections that policy-makers and legislative bodies hold (some of which have been elaborated above). Currently, sewage surveillance and wastewater treatment are not ready to be enforced as methods for developing epidemiological models straight away, owing to the inconsistencies in our knowledge of the analytical and collection operations. Nonetheless, they have undoubtedly improved upon the subsisting programs of a plenty of educational institutions, unfolding a ‘new kind of college test’ that you don’t want to pass!

References Bibby, K. (2020, September 4). How Sewage Monitoring for COVID-19 Works. Science: The Wire. https://science. thewire.in/health/covid-19-testing-sewage-wastewater/.

Brandt, R. (2020, April 2). UArizona Tracking Coronavirus Through Wastewater Across US. University of Arizona News. https://news.arizona.edu/story/uarizona-tracking-coronavirus-through-wastewater-across-us.

Campbell, S., & Epstein, R. H. (2020, April 23).

Why are coronavirus tests so difficult to produce? BBC Future. https://www.bbc.com/future/ article/20200422-why-are-coronavirus-tests-so-difficult-to-produce.

Daley, J. (2020, March 27). Here's How Coronavirus Tests Work-and Who Offers Them. Scientific American. https://www.scientificamerican.com/article/heres-howcoronavirus-tests-work-and-who-offers-them/.

Dotinga, R. (2020, September 7). A New Kind of College Exam: UCSD Is Testing Sewage for COVID-19. Voice of San Diego. https://www.voiceofsandiego.org/topics/ news/ucsd-is-testing-sewage-for-covid-19/.

Eisenberg , M., Brouwer, A., & Eisenberg, J. (2018, October 19). Sewage surveillance is the next frontier in the fight against polio. The Conversation. https://theconversation.com/sewage-surveillance-is-the-next-frontier-inthe-fight-against-polio-105012.

Gill, V. (2020, August 3). Coronavirus: Sewage testing for Covid-19 begins in England. BBC News. https://www. bbc.com/news/science-environment-53635692.

Metcalf, T. G., Melnick, J. L., & Estes, M. K. (1995). Environmental Virology: From Detection of Virus in Sewage and Water by Isolation to Identification by Molecular Biology—A Trip of Over 50 Years. Annual Review of Microbiology, 49, 461–487.

Nierenberg, A., & Pasick, A. (2020, September 9). Schools Briefing: Coronavirus Dorms and Super Spreaders. The New York Times. [Retrieved October 10]. from https://

www.nytimes.com/2020/09/09/us/schools-reopening-coronavirus.html.

Peiser, J. (2020, August 28). The University of Arizona says it caught a dorm's covid-19 outbreak before it started. Its secret weapon: Poop. The Washington Post. [Retrieved October 10]. from https://www.washingtonpost.com/nation/2020/08/28/arizona-coronavirus-wastewater-testing/.

Richtel, M. (2020, August 30). Looking to Reopen, Colleges Become Labs for Coronavirus Tests and Tracking Apps. The New York Times. [Retrieved October 10]. from https://www.nytimes.com/2020/08/30/us/colleges-coronavirus-research.html.

Vuong, K. T. (2020, August 28). Coronavirus Blood Test (antibody) vs. Swab Test (PCR) vs. Rapid COVID Test - Which is Best? Mira. [Retrieved October 10] from https://www.talktomira.com/post/coronavirus-blood-test-antibody-swab-test-pcr-saliva-test-differences.

Whitehurst, L. (2020, September 7). Colleges combating coronavirus turn to stinky savior: sewage. The Denver Post. https://www.denverpost.com/2020/09/07/ colleges-coronavirus-testing-waste-water-sewage/.

Yeo, C., Kaushal, S., & Yeo, D. (2020). Enteric involvement of coronaviruses: is faecal–oral transmission of SARS-CoV-2 possible? The Lancet Gastroenterology & Hepatology, 5(4), 335–337. https://doi.org/10.1016/ s2468-1253(20)30048-0

EDITORIAL

The principal advantage of this form of testing is that it pro-actively traces strands of the virus before individuals start showing symptoms or even if they don’t show symptoms at all. The college crowd is primarily constituted of youth in the age category of 18-24 years. Since the body ideally has a relatively stronger immunity for such people, making it all the more likely not to show any symptoms, such a surveillance strategy can notably aid in mitigating risks. In the first week when University of Arizona carried out the treatment and a sample tested positive, 311 people who lived or worked in the corresponding dorm (Likins Hall) were instantaneously tested. Two asymptomatic students were discovered and immediately quarantined, while others were notified to continue taking precautions.

“You think about if we had missed it, if we had waited until they became symptomatic and they stayed in that dorm for days, or a week, or the whole incubation period, how many other people would have been infected?” said Richard Carmona, a former U.S. surgeon general who is directing the school’s reentry task force, in a news conference (Peiser, 2020). Besides, it acts like an inexpensive preliminary process, limiting the need to test every student on campus and saves essential resources.

“The sewage tests each cost $250 to a few hundred dollars and take about eight hours” (Dotinga, 2020).

2020). In fact, sewage surveillance has diversified to various other countries too, broadening the horizons of its potential utility. In early August, England’s Department of Environment, Food and Rural Affairs announced that sewage testing would be conducted over 44 treatment sites (Gill, 2020). The National Institute for Public Health and the Environment in the Netherlands has declared the same but across over 300 facilities. Some additional countries with such programs include Singapore, China, New Zealand and Canada (Peiser, 2020).

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J which an individual has the virus but does not show any symptoms and tests negative for the disease, that may last between 2-14 days (Clinical questions, 2020). This quality is a major cause of COVID-19 outbreaks; people who have COVID-19 that are in the incubation period and are asymptomatic can still spread the disease. As a result, people unknowingly spread the disease to many others when proper social distancing is not enforced. Social distancing procedures include staying more than 6 feet away from those outside of your household, washing hands frequently, and wearing masks in public spaces (Li et al, 2020).

In the United States and other countries in lockdown, people are told by health organizations and their governments to practice social distancing and stay in their homes and not go to work or school. However, many people go against these recommendations and still see others outside of their households, spreading the virus. What could the United States have done differently to prevent these COVID-19 outbreaks? How did other countries manage to successfully and quickly limit the spread of COVID-19 as opposed to the US?

The most successful tactics found to prevent the spread of COVID-19 in countries around the world were early, centralized, and strictly-enforced measures with contact tracing. Contact tracing is when everyone who has come in contact with someone who tested positive for COVID-19 while they may have had it is informed and gets tested for it as well (Clinical questions, 2020).

COVID-19

Countries that managed to avoid severe COVID-19 outbreaks

Successful Global Strategies Found to Handle the COVID-19 Pandemic

By Anna Feldmen

"The most successful tactics found to prevent the spread of COVID-19 in countries around the world were early, centralized, and strictly-enforced measures with contact tracing."

Since February of 2020, over 273,000 people have died from COVID-19 in the US, and 1.49 million have died worldwide. There were 14 million cases in the US (~3.7% of the total population), some of which led to health complications in the heart, lungs, or brain as a result of the virus (Del Rio, Collins & Malani, 2020). Now, while other countries who were better able to curb the virus’s spread are celebrating a decline in COVID-19 cases, the United States and other countries are still struggling to control the pandemic.

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Common symptoms of COVID-19 include a fever, cough, fatigue, and difficulty breathing, which can be fatal. The symptoms can be mild or extremely severe. The groups which are most at risk for severe symptoms include people over the age of 60 and those with pre-existing medical conditions, particularly lung and heart problems. COVID-19 is primarily spread through respiratory droplets exhaled from an individual’s breath and the resulting aerosol transmission to others, particularly in closed spaces where air is recirculated. This mode of infection is common for many viruses (Li et al, 2020). The difference with COVID-19 is that it has a very long incubation period, the time in

Singapore’s social inequalities hindered the nationwide health

Singapore had a good early response to the virus, but due to the country’s poor conditions for migrants, the country had a large COVID-19 outbreak later into the pandemic. Fortunately, the country has had low death rates due to high testing and the fact that the virus mostly infected younger people who are less likely to die from COVID-19. Like Taiwan, Singapore took COVID-19 seriously because of the previous SARS epidemic. Singapore quickly closed their borders and enforced social distancing, widespread testing, and contact tracing. People were even required to scan their IDs when they went grocery shopping which helped with contact tracing (Bremmer, 2020). As a result of these measures, as of April 9, 2020, the country only had around 1,000 cases (~.02% of the population) and six deaths (How 9 countries, 2020).

Singapore’s official lockdown ended in March of 2020 but people were told to stay inside after that time.

Unfortunately, hundreds of thousands of migrant workers in Singapore live in crowded dormitories. Social distancing is impossible in these dorms as the workers live with up to a dozen other people in the room. These workers do not have good access to healthcare and were not tested for a long period of time. When they were tested, it was revealed that tens of thousands of the workers were infected with COVID-19. The country now has had 58,000 positive cases (~1% of the population), but only 27 deaths (How 9 countries, 2020). The country opened back up for most of its citizens, but many migrant workers are still under quarantine (Tan, 2020).

The limits of current COVID-19 research

It is important to acknowledge that much of the research on COVID-19 is still in development, and was in even earlier stages of the process at the start of the pandemic when countries were creating their initial policies to deal with the virus. Most of the precautionary measures which are now believed to be successful to prevent spreading COVID-19 are those used for similar viruses rather than COVID-19 in particular.

The number of COVID-19 cases reported for a country is dependent upon how widespread the testing is for the country. If a country did not institute widespread testing, it may appear that a smaller percentage of JUST VOL VI // ISSUE I // FALL 2020 13

EDITORIAL

EDITORIAL

Introduction

New Zealand is an example of a country that used these tactics very successfully. The country had its first documented COVID-19 case on February 26, 2020 (Baker, Wilson & Anglemyer, 2020). A week later, the country shut down non-essential businesses — a far quicker response than other countries — and established a “level 4 lockdown” where people could not interact with those outside of their household for the end of March as well as the majority of April and May. The government sent out text messages to citizens to explain the situation and what they should do to prevent COVID-19 from being spread. Furthermore, to help the mental health and financial stability of the population, prime minister Jacinda Ardern promised that no one who lost work during the quarantine would lose their homes and passed various tax reforms to help small businesses while they were closed (Bremmer, 2020). As a result, there were only around 2,000 COVID cases in the country (~0.04% of the population).

Taiwan was also able to keep a very low infection and death rate. Although the country is located right next to China, the origin of COVID-19, it has only had 518 cases (~.002% of the population) and seven deaths (Bremmer, 2020). Taiwan was more prepared to commit to strict actions from its experience in the previous SARS epidemic in 2003 and because their vice president, Lai-Ching Te, is an epidemiologist. During the SARS epidemic, there were 668 cases in Taiwan believed to be SARS, 181 of which were

fatal. The country had a quarantine period to avoid overwhelming their hospitals (Chen et al, 2005). Therefore, after the first COVID-19 cases in the country, Taiwan quickly closed their borders and began contact tracing and using SIM-tracking from the SIM cards in citizen’s phones which connect to cell towers to identify and ensure that people in quarantine were following the guidelines. Businesses were kept open throughout the pandemic but visitors were required to take temperatures and put on hand sanitizer before they could enter businesses such as restaurants or gyms (Bremmer, 2020).

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J the population was infected than the actual percentage.

COVID-19 testing has also been found to have high sensitivity, which is the ability of the test to identify those with the virus, but lower specificity, which means that false positives are somewhat common (Böger, 2020).

Conclusion

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Baker, M. G., Wilson, N., and Anglemyer, A. (2020).

Successful Elimination of Covid-19 Transmission in New Zealand. New England Journal of Medicine, 383(8). doi:10.1056/nejmc2025203 Böger, B., Fachi, M. M., Vilhena, R. O., Cobre, A. F., Tonin, F. S., Pontarolo, R. (2020).

Systematic review with meta-analysis of the accuracy of diagnostic tests for COVID-19. American Journal of Infection Control. doi:10.1016/j.ajic.2020.07.011 Bremmer, I. (2020, June 12). The Best Global Responses to COVID-19 Pandemic. [Retrieved November 3] from https://time.com/5851633/ best-global-responses-covid-19/ Chen, K., Twu, S., Chang, H., Wu, Y., Chen, C., Lin, T., Olsen, S. J., et al. (2005). SARS in Taiwan: An overview and lessons learned. International Journal of Infectious Diseases, 9(2), 77-85. doi:10.1016/j.ijid.2004.04.015 Clinical Questions about COVID-19: Questions and Answers. (2020). [Retrieved November 3] from https://www.cdc.gov/coronavirus/2019-ncov/hcp/ faq.html Del Rio, C., Collins, L. F., Malani, P. (2020). Long-term Health Consequences of COVID-19.

JAMA. 324(17), 1723–1724. doi:10.1001/ jama.2020.19719 How 9 countries responded to Covid-19 and what we can learn to prepare for the second wave.

(2020, May 8). [Retrieved November 3] from h tt p s : / / w w w. a d v i s o r y.co m / re s ea rc h / g l o b a l - fo rum-for-health-care-innovators/the-forum/2020/05/ covid-19-covid-19-responses Li, H., Liu, S. M., Yu, X. H., Tang, S. L., Tang, C. K. (2020).

Coronavirus disease 2019 (COVID-19): current status and future perspectives.

International journal of antimicrobial agents, 55(5). https://doi.org/10.1016/j.ijantimicag.2020.105951 Tan, Y. (2020, September 17). Covid-19 Singapore: A 'pandemic of inequality' exposed.

[Retrieved November 3] from https://www.bbc.com/ news/world-asia-54082861

HEALTH

The Evolutionary Battle Between Bacteria, Antibiotics, and Humans

By Carter Wood "In a world that is limping its way through an unprecedented pandemic crisis, it is more important now than ever before that we give respect and understanding to the invisible inhabitants of the world."

In the fall of 1928, Scottish scientist Sir Alexander Fleming unleashed a groundbreaking scientific discovery, shaping a future with unimaginable consequences (Centers for Disease Control and Prevention, 2020). While Fleming experimented with a common strain of Staphylococcal bacteria, external mold spores that had traveled into the laboratory via an open window contaminated an uncovered petri dish patched with the bacteria. Shockingly, all of the bacteria surrounding these mold spores quickly began to die, leaving behind only the clear agar of the plate (Tan & Tatsmura, 2015, p. 366). Fascinated, Fleming quickly succeeded in his attempts to isolate the mold’s chemical compound, naming it Penicillin

after its membership of the Penicillium genus. This new “miracle drug” boasted the ability to kill previ-

Figure 1. Sir Alexander Fleming inspecting a petri dish. Photo by Fame Images

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EDITORIAL

Countries that were able to successfully counter the COVID-19 pandemic, such as Taiwan and New Zealand, had early, centralized, well-enforced social distancing protocols that utilized contact tracing. Singapore was thought to have been successful until it was found that the nation’s lower class had been infected and had not been tested. The United States resisted significant measures to stop COVID-19 from spreading, had very little centralized action, and no national contact tracing attempt. The results of these countries actions show that in order to deal with a highly infectious, dangerous disease, the primary concern must be on reducing the spread and commitment to action from the citizens — not profit, privacy, or keeping things “normal.”

References:

J

J ously untouchable bacteria, and the first antibiotic drug was born. As the name implies, antibiotics are a specific type of medicine that target and destroy bacterial strains of infection. Upon the initiation of antibiotic use, bacterial infections that were previously fatal to the human population became a fear of the past; average life expectancies rose from 47 years to 78.8 years, the elderly population grew 9% in size, and soon death by infectious diseases virtually disappeared in all but those who were medically compromised (Aldedeji, 2016). However, while effective to the highest

Figure 2. Chemical composition of Penicillin. Image by Wikipedia.

degree upon initial use, the world would soon observe a rapid decrease in efficacy throughout the following years.

Bacteria and Selection

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Figure 3. Charles Darwin, the Father of Natural Selection. Photo by General Photographic Agency/Getty Images.

their aggressors. Every year in the United States more than 2.8 million people are infected by these strains and more than 35,000 people die (Centers for Disease Control and Prevention, 2020). Without antibiotics to stop them, these bacterial strains, known as superbugs, have the ability to run rampant and wreak havoc throughout the human population (Adedeji, 2016).

MRSA and superbugs

they utilized their ability to produce antibiotics (Adedeji, 2016). Through natural selection, bacteria that most effectively produced antibiotics successfully outcompeted those who could not and survived. Mastering an understanding of these abilities may hold the key to creation of new and powerful antibiotics.

However, humans know little to nothing about these abilities due to the sheer massiveness of the bacterial varieties and the countless variables that may influence the production of these antibiotics. In fact, it is estimated that 99% of all bacteria worldwide have yet to have been cultured in a laboratory setting, so research is critical to closing this gap in knowledge (Handelsman & Al., 2018).

Pioneering new antibiotics

Figure 4. The process of Horizontal Gene Transfer in bacteria. Image by MDPI.

Methicillin-resistant Staphylococcus aureus (commonly referred to as MRSA) is a real-world example of bacterial evolution against antibiotics. MRSA is a terrifying disease that gives rise to serious global health concerns in both developed and developing countries, with a disproportionate effect on poor and minority communities. Staphylococcus aureus, the bacteria responsible for causing MRSA, is estimated to be carried by 33% of people globally, with approximately 2% of these people carrying its deadly, resistant strain (Center for Disease Control, 2019). Capable of living for extended periods of time on most surfaces, MRSA is passed person to person by touch, both directly and indirectly. When contaminated with MRSA’s resistant bacterial strain, one will experience a wide variety of symptoms, ranging from skin infections, pneumonia, sepsis or death (Center for Disease Control, 2019).

Since MRSA has developed resistance to most antibiotics, preventative efforts are critical to limit its spread and effective treatments rely on attacking the bacterium with new antibiotics in an attempt to penetrate its metaphorical armor. It is because of super bugs such as MRSA that research into the development of new antibiotic drugs is of the utmost importance. Without it, the human species stands vulnerable to these microscopic invaders who boast the ability to devastate entire communities. What solutions are there for us to explore? Strikingly, we can use microbes and their evolution against them. During their billions of years of evolution, bacteria were forced to fight for survival against competition among themselves, and to do so

Projects such as Tiny Earth, a worldwide scientific investigation into antibiotic discovery headquartered at the University of Wisconsin-Madison, aims to discover these hidden secrets from the soil and use them to pioneer new antibiotics. Worldwide, Tiny Earth is a force of 10,000 undergraduate students throughout 45 countries, all of whom are attempting to discover novel compounds that can become the next productive antibiotic. Here, at the University of Wisconsin-Madison, Dr. Josh Pultorak, PhD, leads students in studying variables such as a bacterium’s chemical environment, soil pH, rhizosphere relationships with plants, and use of fertilizer to investigate how they may spark antibiotic production of soil microbes.

My research this semester with Tiny Earth, overseen

by Dr. Pultorak, has focused on how the presence of caffeine, the world’s most commonly consumed psy-

Figure 5. Methicillin-resistant Staphylococcus aureus (MRSA). Image by Wikipedia.

choactive drug, affects antibiotic production within a colony of bacteria (Caffeine, 2003). By researching the variables that impact bacteria and their antibiotic production, Tiny Earth hopes to close the enormous knowledge gap regarding soil microbes and their anJUST VOL VI // ISSUE I // FALL 2020 17

EDITORIAL

Bacteria, one of the three domains within the tree of life, are single-celled prokaryotic microbes that are present in our world in mind blowing numbers (Libretexts, 2020). Current estimations of worldwide bacterial abundance tops five million trillion trillion (5x1030) bacteria, with more than thirty-eight trillion bacteria residing in every human (Lehman, 2017; McKeon, 2016). These bacteria are believed to be the first lifeforms to exist and have been present and adapting throughout the billions of years of our planet’s evolution, long before even the most ancient of human ancestors. During these billions of years, bacteria underwent intense natural selection to hone advantageous traits and eliminate deleterious ones, strengthening and fortifying their survival abilities.

Natural selection is a fundamentally critical idea in the field of biology. First proposed by Charles Darwin in his 1859 publication of On the Origin of Species, natural selection has shaped how we view the evolution of our world (National Human Genome Research Institute, 2013). Simply stated, natural selection is the idea that the environment will determine which characteristics of a population, either physical or genetic, are best suited for survival. If advantageous or contributive to survival, organisms with these ben-

eficial characteristics will pass their genetic composition to their offspring, who will display the same advantageous characteristics. However, if an organism has deleterious characteristics, natural selection will remove the individual, their characteristics, and genetic alleles from the population to prevent the inheritance of their genes. In this manner, a population will evolve over time, adapt, and become increasingly fit for survival. Bacteria are no exception and have undergone intense selections themselves. Characteristics that allowed them to reside in hostile environments, effectively reproduce, and beat out their opposing bacterial competitors all became quintessential to survival (Adedeji, 2016). Thus, it is not a surprise to see that today’s bacteria, like their ancient prokaryotic ancestors, adapt to their most current threat: antibiotics. This process, coined antibiotic resistance, is an evolutionary, natural selection process during which the weakest bacteria are eliminated from a human host, but the strongest bacteria, the ones with the ability to fight the antibiotic drug, remain. These bacteria are genetically diverse from the others and display the capability to outmaneuver antibiotics and survive their attack (Adedeji, 2016). When these organisms multiply, they create extensive networks of antibiotic resistant microbes, all of which reproduce exponentially, to create entirely new strains of stronger, more treacherous microbes with antibiotic resistant properties (Mayo Clinic, 2020).

More dangerous yet is the fact that bacteria possess the ability to swap DNA among themselves without physical reproduction. This process, called Horizontal Gene Transfer, enables a bacterium to acquire genes from other bacteria in their environment, further enhancing the probability that resistant gene frequencies will be amplified (Handelsman & Al., 2018, p. 100). These bacteria go on to infect humans who no longer have the adequate medicinal tools to fight

J

J tibiotic abilities (Tiny Earth, 2020). The fight against antibiotic resistance, however, does not solely rely on the scientists of the world; every individual has a part

Figure 6. Dr. Joshua Pultorak, PhD and myself in the University of Wisconsin-Madison Tiny Earth Laboratory. Photo by Lauren Simone.

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References: Adedeji, W. A. (2016, December 1). The treasure called antibiotics. PubMed Central (PMC). https://www.ncbi. nlm.nih.gov/pmc/articles/PMC5354621/ Caffeine. (2003). CAMH. https://www.camh.ca/en/ health-info/mental-illness-and-addiction-index/caffeine Centers for Disease Control. (2019, February 28).

Healthcare Settings | MRSA | CDC. Centers Foro Disease Control and Prevention. https://www.cdc.gov/ mrsa/healthcare/index.html Centers for Disease Control and Prevention.

(2020, March 13). What Exactly is Antibiotic Resistance?https://www.cdc.gov/drugresistance/about.html Fame Images. (2017, August 7). Sir Alexander Fleming inspects a petri dish full of bacteria [Photograph]. Business Insider. https://www.businessinsider.com/alexander-fleming-predicted-post-antibiotic-era-70-years-ago-2015-7

gin-of-species-proposing-continual-evolution-of-species Tan, S. Y., & Tatsumura, Y. (2015). Alexander Fleming (1881–1955): Discoverer of penicillin. Singapore Medical Journal, 56(07), 366–367. https://doi.org/10.11622/ smedj.2015105 Tiny Earth. (2020, July 20). Our Network. https://tinyearth.wisc.edu/about-us/our-network/ Wikipedia. (2020a, October 1). Penicillin [Illustration].

Wikipedia. https://en.wikipedia.org/wiki/Penicillin Wikipedia. (2020b, October 21). Staphylococcus aureus [Illustration]. Wikipedia. https://en.wikipedia. org/wiki/Staphylococcus_aureus

General Photographic Agency/Getty Images. (2019, December 2). Charles Darwin [Photograph]. NewsWeek. https://www.newsweek.com/charles-darwinday-birthday-quotes-1328085 Handelsman, J., & Al., E. (2018). Tiny Earth - A Research Guide to Studentsourcing Antibiotic Discovery (Print plus e-Book access). XanEdu Publishing Inc. Horizontal Transfer Mechanisms. (2019). [Illustration].

MPDI. https://www.mdpi.com/2076-2607/7/9/363/htm Lehman, C. (2017, April 24). How Many Bacteria Live on Earth? Sciencing. https://sciencing.com/how-manybacteria-live-earth-4674401.html Libretexts. (2020, August 15). 1.3: Classification - The Three Domain System. Biology LibreTexts. https://bio. libretexts.org/Bookshelves/Microbiology/Book%3A_ Microbiology_(Kaiser)/Unit_1%3A_Introduction_ to_Microbiology_and_Prokaryotic_Cell_Anatomy/1%3A_Fundamentals_of_Microbiology/1.3%3A_ Classification_-_The_Three_Domain_System Mayo Clinic. (2020, February 15). Antibiotics: Are you misusing them? https://www.mayoclinic.org/ healthy-lifestyle/consumer-health/in-depth/antibiotics/art-20045720?reDate=11102020&reDate=04112020 McKeon, D. (2016, January 20). How many bacteria vs human cells are in the body? The American Microbiome Institute. http://www.microbiomeinstitute.org/ blog/2016/1/20/how-many-bacterial-vs-human-cellsare-in-the-body National Human Genome Research Institute. (2013, April 22). 1859: Darwin Published On the Origin of Species, Proposing Continual Evolution of Species.

Genome.Gov. https://www.genome.gov/25520157/online-education-kit-1859-darwin-published-on-the-ori-

EDITORIAL

to play and possesses the power to influence the outcome of this crisis. Most importantly, we must strive to raise awareness regarding the dangers of antibiotic resistance, and only then can steps be taken to help prevent it. According to the Centers for Disease Control, an estimated one half of all antibiotics are used in an inappropriate manner, establishing the environment needed for resistant strains to emerge (Mayo Clinic, 2020). What qualifies as inappropriate usage, and how can it be prevented? First and foremost, slowing down inappropriate usage can be accomplished by a fundamental comprehension of what sicknesses antibiotics are designed to attack. Antibiotics, which only are effective against bacterial illnesses, are completely powerless against viruses such as the common cold, the flu, and viral infections (Mayo Clinic, 2020). Therefore, you must consult a medical professional before taking antibiotics to treat a sickness that may not be impacted by their use. By ignoring this, you run the risk of killing helpful bacteria and allow the possibility that resistant bacterial strains will proliferate (Mayo Clinic, 2020). If prescribed antibiotics, be sure to take them throughout the full course of the treatment, do not stop simply because symptoms have abated, and never take left over antibiotic prescriptions unsupervised at a later date. These steps will ensure that all of the bacteria being targeted will be eliminated and no po-

tentially dangerous organisms are left behind.

Outside of physical interactions with antibiotics, everyday precautionary measures must be realized and executed. Preventive measures such as personal hygiene, food quality standards, and medical vaccinations all play a key role in stopping infections before antibiotics are ever needed. Educating the general public, friends, and family is critical in the campaign to prevent antibiotic misuse and correct the common misunderstandings that go along with it.

The campaign to battle misinformation, spread antibiotic awareness, and raise environmental health standards is one that the government also must step in and direct. Investments in public health policies and programs that regulate antibiotic usage is a phenomenal path to transparency and dedication to the upholding of ethical distributions of the drugs (Adedeji, 2016). If these key ideas are followed, the lifespan of our current antibiotics can be significantly expanded.

More time means less sickness, less death, and more opportunities for researchers to isolate new antibiotic compounds that have the potential to save countless lives.

In a world that is limping its way through an unprecedented pandemic crisis, it is more important now than ever before that we give respect and understanding to the invisible inhabitants of the world.

The overuse of antibiotics, and the resistance that undoubtedly will occur, is an unprecedented threat to global health and is one that requires our immediate attention if we are to save the lives of future generations. While truly a difficult undertaking, the curbing of inappropriate usage of antibiotics, adjusting lifestyles, and advancing research into the field of antibiotic compounds is one that we all can undertake together to ensure safer and brighter future for generations to come.

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J been at the forefront of novel chemical biology research in order to better understand the methods that bacteria employ to communicate between cells, and the implications that this communication has on their virulence.

Many bacteria have the ability to coordinate group behaviors via a chemical communication system known as quorum sensing (QS). Bacteria are typically divided into Gram-positive and Gram-negative bacteria, broad classifications that stem from key differences in the composition of their respective cell walls. Generally speaking, the cell wall of a Gram-positive bacterium is thicker and more robust as a result of higher amounts of the sugar/amino acid polymer peptidoglycan, while the cell wall of a Gram-negative bacterium consists of a thin plasma membrane.

This structural discrepancy between cell walls results in a plethora of differences in how these bacteria function.

However, the focus of this review will surround QS systems in bacteria: more specifically, QS in Gram-negative bacteria.

BIOLOGY

Signal Regulation

The Importance of Interrupting Bacterial Conversations

By Michael Kuehne

"Similar to human beings, bacteria have evolved methods of communication within local populations that allow them to complete certain tasks that would be impossible for a lone cell to accomplish, such as infecting a macroscopic host."

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(World Health Organization, 2018).

Not only this, antibiotic resistant bacteria actively contribute to the growing antibiotic crisis, rendering traditional treatment of infections progressively more ineffective (Brown & Wright, 2016). This looming threat to public health has prompted the development of new methods with which to combat bacterial infection; the targeting of their communication systems has been an especially promising avenue for attenuating the virulence (i.e., the ability to initiate infections) of these pathogens (Clatworthy, Pierson, and Hung, 2007). Here in the Department of Chemistry at UW–Madison, the Blackwell lab has

Bioluminescence

In the case of V. fischeri, the result of this autoinduction pathway is bioluminescence (Fuqua and Greenberg, 1994). The practical use of this bioluminescence in nature by the Hawaiian bobtail squid — V. fischeri’s bacterial host — is quite astounding. Hawaiian bobtail squids are nocturnal creatures and prefer to hunt under the light of the moon. In the shallow waters in which these squids hunt, the moonlight casts looming shadows of any suspended marine animal on to the sand, giving away their location to other nearby animals. However, hosting the V. fischeri within a special bioluminescent light organ in its mantle allows for the squid to essentially cancel out the light of the moon and to prevent this shadow from ever being cast, symbiotically aiding in the survival of both the host and of the V. fischeri colony. Ever since this discovery, the LuxI/LuxR-type family has expanded considerably, now including well-known pathogens such as Pseudomonas aeruginosa, the Burkholderia cepacia complex (Bcc), as well as many others. This review will cover the QS-blocking strategies of both P. aeruginosa and of a specific Bcc member, B. multivorans.

Since AHLs are the native chemical signals with which these bacteria communicate in a LuxI/LuxR QS circuit, elucidating their structure is an imperative step in determining a host of QS-related information regarding that bacterium, such as how the AHL may bind to the receptor-site. This information allows biochemists to make more accurate inferences about how bacteria perceive signals from surrounding cells, resulting in more educated guesses regarding possible methods of attenuating and/or modulating this communication.

AHL Analogs

An intuitive starting point of QS modulation is synthesizing molecules with a similar chemical structure to the AHL, or synthesizing AHL-analogs — since the bacteria already recognizes the native signal, a molecule similar in structure may directly compete with AHLs at the binding site or modulate QS in a more discreet and indirect manner. After synthesis, these AHL-analogs are tested in relevant bacterial reporter assays to collect data regarding their efficacy as QS modulators in that respective bacterium. This process can be repeated to elicit subsequent generations of modulators that build upon the failures and successes of the last, with the hopes of yielding increasingly potent QS modulators — the more we can

EDITORIAL

Yes, you read that correctly — bacterial conversations. Similar to human beings, bacteria have evolved methods of communication within local populations that allow them to complete certain tasks that would be impossible for a lone cell to accomplish, such as infecting a macroscopic host. The infections engendered by these opportunistic bacterial pathogens (i.e., disease-causing bacteria that capitalize on hosts with weakened immune systems) are proving to be an increasingly dangerous threat to human health in our society — despite the widespread onset and distribution of antibiotics in the mid-twentieth century, infection remains a major source of death globally

The cell-to-cell signaling processes of QS in Gram-negative bacteria are largely regulated by diffusible chemical signals called N-acylated homoserine lactones (AHLs), which are produced by “LuxI-type” synthases within the cell — in an analogy to human language, think of AHLs as the “words” that bacteria use to speak, and of LuxI-type synthases as the “mouths” employed to verbalize these words. Once produced, these AHLs are released into the surrounding cellular environment, where they can diffuse through the plasma membrane of nearby bacteria. At this point, these chemical signals are perceived by complementary LuxR-type receptors (Miller and Bassler, 2001) — think of the LuxR-type receptors as the “ear” and “brain” of the bacteria that recognize and subsequently conceptualize the words of the surrounding bacteria. Decades of research have been poured into the field of QS that serve to validify the science behind this analogy, ultimately lending a clear description of the ways in which our microscopic counterparts are able to effectively infect.

These LuxI/LuxR-type QS circuits allow for the regulation of gene expression once certain environmental conditions are reached — typically a “threshold” concentration of AHLs at corresponding high cell densities. Once this threshold concentration is achieved (i.e., a “quorum” is sensed) the bacteria are able to express a plethora of group behaviors that promote their survival, including: virulence factors, antibiotic resistance, biofilm formation, bioluminescence, etc. (Rutherford and Bassler, 2012). Although these QS-related phenotypes are highly diverse and dependent on the capability and/or needs of the bacteria in question, this review will largely focus on virulence and the implications

The “LuxI/LuxR” terminology alludes to the lux gene in Vibrio fischeri — the bacterium in which QS was first observed — and the corresponding “autoinduction” (i.e., environmental self-sensing of population density via an AHL signal) of the gene responsible for the expression of V. fischeri’s characteristic bioluminescence. The lux

gene is a transcriptional activator within V. fischeri that is dependent on the cell-density and corresponding concentration of AHL signal in the cellular environment —in other words, lux has very low levels of gene expression in low-to-mid-levels of autoinducer, but its expression rapidly increases upon reaching a certain point (level?) of signal. This can intuitively be thought of as the bacteria’s way of “biding its time” to ensure there are sufficient levels of surrounding bacteria present to successfully express the target gene.

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J control how these bacteria communicate, the closer we can get to understanding and halting the deadly infections that they cause. Each generation of QS modulators are typically analyzed for agonism (i.e., the ability to turn on QS) and antagonism (i.e., the ability to turn off QS). Although agonists can be important for delineating QS mechanisms, antagonists are generally the targets of these studies.

An antagonist’s efficacy is judged by its IC50 value in a relevant cell-reporter assay; the IC50, or the half-maximal inhibitory concentration, is the amount of compound needed to inhibit 50% of the QS activity when competing against a fixed amount of native AHL. Broadly speaking, an antagonist is considered potent if it has a single-digit micromolar IC50 value, although this can vary across different LuxR-type receptors. Another important measurement of potency is the maximum inhibition percentage, which is simply a measurement of the how much of the QS activity of the native signal the antagonist is able to suppress — 100% implying zero native QS activity for that antagonist in question.

Recent Findings

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References Bottomley, M.J., Muraglia, E., Bazzo, R., and Carfi, A. (2007).

Molecular insights into quorum sensing in the human pathogen Pseudomonas aeruginosa from the structure of the virulence regulator LasR bound to its autoinducer. Journal of Biological Chemistry.

282(18), 13592-600.

Boursier, M.E., Combs, J.B., Blackwell, H.E. (2019). N-Acyl L-Homocysteine Thiolactones Are Potent and Stable Synthetic Modulators of the RhlR Quorum Sensing Receptor in Pseudomonas aeruginosa. ACS Chemical Biology. 14(2), 186-191.

Brown, E.D. & Wright, G.D. (2016). Antibacterial drug discovery in the resistance era. Nature.

529(7586), 336-343.

Welsh, M.A. & Blackwell, H.E. (2016). Chemical Genetics Reveals Environment-Specific Roles for Quorum Sensing Circuits in Pseudomonas aeruginosa.

Cell Chemical Biology. 23(3), 317-318.

World Health Organization Global Health Observatory Data. 2018 Mortality and Global Health Estimates [cited 2020, August 29]. Available from: https://www.who.int/gho/mortality_burden_disease/en/.

Wysoczynski-Horita, Boursier, M.E., Hill, R., Hansen, K., Blackwell, H.E., and Churchill, M.E.A. (2018). Mechanism of agonism and antagonism of the Pseudomonas aeruginosa quorum sensing regulator QscR with non‐native ligands. Molecular Microbiology.

108(3), 240-257.

Clatworthy, A.E., Pierson, E., and Hung, D.T. (2007). Targeting virulence: a new paradigm for antimicrobial therapy. Nature Chemical Biology. 3(9), 541548.

Fuqua, C.W. & Greenberg, E.P. (1994). Quorum Sensing in Bacteria: the LuxR-LuxI Family of Cell Density-Responsive Transcriptional Regulators. The Journal of Bacteriology. 176(2), 269-275.

Goven, J.R., Brown, A.R., Jones, A.M. (2007). Evolving epidemiology of Pseudomonas aeruginosa and the Burkholderia cepacia complex in cystic fibrosis lung infection. Future Microbiology. 2(2), 153-164.

Manson, D.E., O'Reilly, M.C., Nyffeler, K.E., Blackwell, H.E. (2020). Design, Synthesis, and Biochemical Characterization of Non-Native Antagonists of the Pseudomonas aeruginosa Quorum Sensing Receptor LasR with Nanomolar IC50 Values. ACS Infectious Diseases. 6(4), 649-661.

Miller, M.B. & Bassler, B.L. (2001). Quorum Sensing in Bacteria. Annual Review of Microbiology. 55, 165-199.

Peralta, D.P., Chang, A.Y., Ariza-Hutchinson A., and Ho, C.A. (2018). Burkholderia multivorans: A rare yet emerging cause of bacterial meningitis. IDCases. 11, 61-63.

Rutherford, S.T. & Bassler, B.L. (2012). Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harbor Perspectives in Medicine. 2(11).

Slinger, B.L., Deay, J.J., Chandler, J.R., and Blackwell, H.E. (2019). Potent modulation of the CepR quorum sensing receptor and virulence in a Burkholderia cepacia complex member using non-native lactone ligands. Scientific Reports. 9(1), 1-12.

EDITORIAL

The QS systems of opportunistic pathogen P. aeruginosa have served as a staple of the Blackwell lab’s research for well over a decade. The ability of P. aeruginosa to form biofilms aids in its intrinsic ability to resist antibiotics in concentrations that would normally be deadly for the bacteria. Biofilms, or slimy conglomerations of bacteria that effectively shelter the bacteria from harmful environmental factors (dental plaque is well-known biofilm), render P. aeruginosa infections especially dangerous to immunocompromised individuals, burn victims, and those generally afflicted with chronic pulmonary disorders (Bottomley, Muraglia, Bazzo, and Carfi, 2007). The QS system of P. aeruginosa is decidedly complex — for the sake of this review, our understanding need only to extend to the fact that there are three Lux-R-type receptors: LasR, QscR, and RhlR. In this system, LasR and QscR are regulated by the same AHL while RhlR is regulated by a different AHL (Welsh & Blackwell, 2016). Although these systems have been found to work conjunctively, the LasI/LasR circuit has been shown to be at the top of the QS hierarchy in P. aeruginosa and has proportionately received the most attention in the literature (Boursier, Combs, and Blackwell, 2019).

A recent 2020 publication from the Blackwell lab reported on a set of non-native LasR antagonists based on the structure of “V-06-018”, a compound with single-digit micromolar IC50 value of 2.3 µM and a maximum inhibition of 89% in LasR. Recall that a single-digit micromolar IC50 value is impressive in its own right and is generally considered to be a potent modulator of QS in that system.

Exemplifying the previously described process of synthesizing AHL-analogs to create more potent modulators, researchers in the Blackwell lab recognized the potential of V-06-018 as a base-molecule from which to synthesize its own respective analogs. Thus, a collection of V-06-018-analogs were synthesized and screened, and the result were compounds possessing sub-micromolar (i.e., nanomolar)

IC50 values as low as 0.2 µM and with a 93% inhibition (Manson, O'Reilly, Nyffeler, and Blackwell, 2020). These are the most potent LasR inhibitors to have been reported in the literature to this date — remember that progress in the field of QS modulation is measured by how effectively we can control these systems. This result signifies progress toward controlling P. aeruginosa infections and illustrates the high standard of research that takes place at UW–Madison. Strangely enough, these non-native compounds had little activity in QscR or RhlR, leaving the door open for further research and speculation regarding the QS circuitry of P. aeruginosa.

Characterizing the QS mechanisms surrounding QscR and RhlI/RhlR has received much less scrutiny in the literature. However, a 2018 study by the Blackwell group reports a novel AHL-analog with an IC50 value of 0.026 µM and 80% inhibition, also making it the most potent QscR antagonist at the time of its publication (Wysoczynski-Horita, Boursier, Hill, et al., 2018). Additionally, a 2019 study by the Blackwell group reports a RhlR antagonist with an IC50 value of ~20 µM and 85% inhibition: one of the most potent RhlR antagonists reported (Boursier, Combs, and Blackwell, 2019). Recall that the QS systems of P. aeruginosa are exceedingly complex in nature — hence, possessing potent QS antagonists of each LuxR-type receptor in P. aeruginosa does not necessarily equate to immediate real-world solutions for fighting its deadly infections.

However, developing these compounds that separately modulate each major LuxR-type receptor in P. aeruginosa is nonetheless an important step toward more holistic QS-blocking strategies in the future.

The Burkholderia cepacia complex (Bcc) is a family of closely related, multi-drug resistant bacterial pathogens that has also been a recent target of QS-blocking strategies (Slinger, Deay, Chandler, and Blackwell, 2019).

Virulence in Bcc species has shown to be regulated by the CepI/CepR QS system, which is mediated by the N-octanoyl L-homoserine lactone (OHL) signal. Along with P. aeruginosa, certain members of the Bcc are opportunistic pathogens commonly found in infections associated with cystic fibrosis (Goven, Brown, and Jones, 2007) and central nervous system infections (Peralta, Chang, Ariza-Hutchinson, and Ho, 2018). In a 2019 publication, the Blackwell lab reported an analog of the native ligand OHL with an IC50 value of 1.7 µM and a 82% inhibition (Slinger, Deay, Chandler, and Blackwell, 2019). This is a promisingly potent IC50 value for a QS system relative to the low amount of scrutiny CepR has received in the literature.

These data regarding the potent inhibition of select QS circuits of P. aeruginosa and B. multivorans are encouraging for future generations of QS inhibition in these bacteria. Amassing a greater number of QS modulators for a variety of LuxR-type receptors at higher potencies allows for a better understanding of virulence in these pathogens, which could lead to potentially life-saving treatments in the near future. Bacteria have been talking in this microbial world of ours long before humanity ever came into being — the Blackwell lab at UW–Madison is finally finding ways to listen in on these conversations.

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J response. Additionally, subunit vaccines often utilize recombinant DNA technology. The DNA that provides the blueprint for creating certain viral subunits can be added to different organisms, such as bacteria or yeast, which in turn produce the specific subunit (Vaccine Types). Currently, the US government is funding the development two subunit vaccines: the Sanofi and GlaxoSmithKline (GSK) vaccine and the Novavax vaccine. Both use COVID-19 proteins, but the Sanofi and GSK vaccine also adds an adjuvant, or an immune boosting ingredient common in subunit vaccines (Corum, Jonathan, et al, 2020).

Nucleic Acid Vaccines

COVID-19

Figure 1: The virus that causes COVID-19 under an electron microscope. Photo credit: NIAID-RML

response the next time the pathogen is encountered, meaning little to no symptoms result from exposure to the same pathogen twice (Zepp, 2010). The challenge in creating an effective vaccine is to recreate this specific immune response without actually making someone sick. Multiple vaccines that achieve this response are currently in use or development, each with unique characteristics that create different challenges and advantages. They are whole pathogen, subunit, and nucleic acid vaccines.

Vaccine Development: A Comprehensive Review for the COVID Age

By Lydia Larsen

"The desire to return to a normal economy, college experience and restaurant dining is nearly palpable on the socially-distanced streets. But the magic spell to achieve normality is not magic at all, and rather, a vaccine."

EDITORIAL

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cess, and the future of vaccine and pharmaceutical development, one must first consider vaccine development pre-pandemic compared to the framework for accelerated SARS-CoV-2 vaccine development.

Types of Vaccines

The vaccine model provided in most high school biology classes, a dead form of virus enters body and creates immunity, encapsulates the general premise of immunity via vaccine. More specifically, the adaptive immune system recognizes a pathogen’s unique antigen, or specific physical component of a pathogen, and elicits a highly specific immune response that terminates the pathogen.

What makes the adaptive immune response remarkable is the “immune memory” it creates, which establishes a stronger and faster

Subunit Vaccines

Subunit vaccines only include critical, identifying parts of a pathogen that the immune system recognizes as an antigen.

Compared to whole pathogen vaccines, they are much less likely to cause any side effects. The subunits used vary greatly among different pathogens. Vaccines developed to prevent certain bacterial infections use identifying polysaccharides (sugars) on the surface of the bacteria as the antigen. Toxoid vaccines contain inactivated forms of toxin produced by pathogenic bacteria, so they don’t cause illness, but are recognized as an antigen.

Other Virus Like Particles (VLPs) and nanoparticles are used as subunits as well. These subunits are sometimes combined to create a conjugate vaccine, which facilitates a better immune

Clinical Trials

For a vaccine to be approved for widespread use in humans, it must first be put through a rigorous testing period to evaluate its safety, effective dosage, and actual immune response. The first step is pre-clinical trials which have in vitro, in a test tube, and in vivo, or animal testing, stages to gather preliminary data. If appropriate, the next step is human clinical trials closely monitored by regulatory agencies such as the Food and Drug Administration (FDA) and the World Health Organization (WHO). Each vaccine’s path through clinical trials is unique since its route depends on the type of vaccine, the pathogen it’s designed to protect against, and other determining factors (Singh, 2016).

EDITORIAL

The advent COVID-19 has upended the various social, educational, fiscal, and familial institutions we once took for granted.

Within the span of a month the pandemic moved education, jobs, and social interaction to Zoom, or completely removed them from our lives. The desire to return to a normal economy, college experience and restaurant dining is nearly palpable on the socially-distanced streets. But the magic spell to achieve normality is not magic at all, and rather, a vaccine.

The race to develop a SARS-CoV-2 vaccine has been on for months in the form of Operation Warp Speed, the Trump administration’s fast track to a successful vaccine. Understanding the nature and efficacy of the operation through news casts is difficult without a background on clinical development. To understand the path to suc-

Whole Pathogen Vaccines

Whole pathogen vaccines, the most traditional and widespread vaccine type, are made of a whole, altered pathogen. The most basic form is the inactivated vaccine created using heat, radiation, or chemicals to render the virus incapable of functioning or replicating (Vaccine Types). On the other hand, live attenuated vaccines are made with a live pathogen weakened in vitro, or in a test tube using non-human tissue. Changes to the pathogen’s DNA render it non-pathogenic, but still replicable in human cells. Because it can still replicate in human cells, the inactivated virus mimics a natural infection. Immune responses from live attenuated viruses create a strong, lasting response in just one to two doses (Zepp, 2010.) The last type of whole pathogen vaccine is the chimeric vaccine, which combines the genetic material and physical components of two pathogens to develop immunity against one illness. For example, the backbone of the vaccine is from one virus, but it displays the antigens of another for the purpose of initiating an immune response (Vaccine Types).

Nucleic acid vaccines introduce genetic material, such as DNA or RNA, containing the blueprint for an antigen to a patient’s cells. The body then produces these antigens with their own cellular machinery and the immune response proceeds as usual. This type of vaccine is quite new, but it holds much promise because of its ability to ensure a much longer-term response in the host’s immune system.

Additionally, the process by which the nucleic acids are created is well understood and common in biological research.

DNA plasmids, small circular pieces of DNA, are the most promising form of nucleic acid vaccine but there is strong evidence that mRNA, an intermediate between DNA and proteins (antigens are often proteins) could be useful as well (Vaccine Types). Currently, the US government is helping fund the development of two mRNA vaccines: the Moderna and Pfizer vaccines. Recently released preliminary data shows the Pfizer vaccine is more than 90% effective in preventing the virus and the Moderna vaccine is about 94% effective.

Experts are hopeful that they may become available in the coming months (Corum, Jonathan, et al, 2020). Additionally, a vector, such as a nonhazardous bacteria or virus, can provide genetic material to the cell instead of directly delivering the DNA or RNA (Vaccine Types).

This recombinant vector vaccine platform is also being used to create a COVID-19 vaccine. Currently, the US government is helping fund the development of the AstraZeneca and Oxford vaccine, the Merck and IAVI vaccine, and the Johnson & Johnson vaccine, all of which use the recombinant vector platform (Corum, Jonathan, et al, 2020).

Phase I

Because vaccines are administered to humans for the first time in Phase I clinical trials, they are usually conducted only on a small group of healthy adults. The purpose is to assess safety and reactogenicity, or the vaccine’s ability to cause “normal” adverse reactions caused by vaccines.

If the initial adult study is successful, then developers assess other factors, such as dosage, and schedule in subsequent Phase Ib studies on different subject populations. The data collected from

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J Phase I studies must follow a standardized approach, usually in an open label format, meaning the researcher and research subject know which treatment the subject receives.

Phase II

If Phase I is successful, developers move to much larger Phase II studies with several hundred to thousands of research participants. Because more participants and resources are involved, Phase II requires more funding and therefore has much stricter progression requirements. The larger number of participants also allows more statistical confidence in the assessment of safety, immune response, and assessments on the likelihood of protection against a pathogen.

Also, Phase II trials can finalize the dosage and vaccination schedule in preparation for the final Phase III. This assessment is accomplished through Random Control Trials (RCTs), meaning study participants randomly receive either the vaccine in question or a placebo. It may appear that Phase II and Phase I are remarkably similar, and in many cases this assessment is correct. However, Phase II studies are better designed, and results are more reliable due to the larger population of study participants. (Singh, 2016).

EDITORIAL

Vaccine Development in the age of COVID-19 and Operation Warp Speed

Early in the pandemic, politicians and public health officials saw a clear need to develop a SARS-CoV-19 vaccine. Scientists have faced demanding vaccine timetables before, but the COVID-19 schedule is drastically abbreviated. When the H1N1 virus became problematic in the northern hemisphere in 2009, scientists developed a vaccine relatively quickly. This was largely due to well-established research and regulation on influenza vaccines. While the

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Operation “Warp Speed:” An Overview

The Trump administration unveiled plans for Operation Warp Speed (OWS) in late May 2020. The goal of the initiative is to develop, produce, and distribute 300 million doses of an effective COVID-19 vaccine by early 2021. It is a partnership between different arms of the Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority (BARDA), the FDA, the National Institutes of Health (NIH), the Department of Defense (DoD), various private companies, and other national agencies.

Funding for the massive project comes from Congress, specifically the CARES act, and is estimated at around 10 billion dollars (Fact Sheet, 2020). The framework of the initiative falls into three categories: development, production, and distribution. Each step is streamlined and regulated differently than for past vaccine trials and some steps occur simultaneously to achieve a faster outcome.

Development

The federal government supervises the regulation and framework of the COVID-19 trials instead of the public-private partnerships found in customary vaccine development. Different research groups and corporations developed possible vaccine candidates and the federal government chose which to support. A diverse group of seven promising vaccines candidates were deemed fit to undergo further testing and eventually the large-scale safety and efficiency trials (Fact sheet, 2020). The University of Wisconsin School of Medicine and Public health is currently a testing site for the Phase III trial of one of these candidates, the AstraZeneca vaccine (UW-Madison School of Medicine and Public Health, 2020).

COVID-19 vaccine safety and efficacy tests are combined in different ways during Phase I, II, and III trials. Specifically, the first time a vaccine is given to research participants it is done by the hundreds (Corum, 2020), not the small scale 15-20 people usually found in Phase I trials. To support this step, scientists used multiple animal models to evaluate vaccine safety and efficacy (Fact sheet, 2020).

Production Under normal circumstances, manufacturing methods for vaccines intensify only after authorization by regulatory groups. Under OWS, the manufacturing framework was created while researchers were still testing vaccines (Fact Sheet, 2020). Whichever vaccine eventually passes its clinical trials will be produced in the manufacturing plant designed and built during its development (Fact Sheet, 2020).

This process is very complicated and financially risky. Vaccine man-

ufacturing plants are highly specific to the type of vaccine they produce and usually take at least 5 years to build. Officials hope to repurpose existing manufacturing plants for COVID-19, or, if necessary, build them. The Bill and Melinda Gates foundation has committed to building seven such facilities, and readily acknowledges that at most two will be used (Thompson, 2020). OWS also dictates that manufacturers will start to produce vaccines before clinical trials are complete, so they are ready to go immediately after approval (Norman, 2020). Operation Warp Speed, in exchange for funding the development and manufacturing of a successful vaccine, gets over 100

set, enough for 3-5% of the US population. The consensus among bioethicists is that frontline health care workers should be the first to receive the vaccine. But choosing those healthcare workers is more complicated than initially anticipated. Obviously, there are nurses and doctors, but there are also the people who clean the hospitals, administrative staff who work in health centers, and even funeral home workers, all of whom hold some claim to the first vaccines.

Beyond health care, experts determine that the adults who receive the first doses should live or work in an environment with a high risk of exposure, including the elderly, and workers necessary to maintain the economy and health of the nation. Ultimately, this adds up to about half of all US adults, much more than initially anticipated (Huang, 2020). Overlapping technical issues, infrastructure challenges, and debates about who should receive the first doses pose very complex ethical dilemmas.

Regardless of political affiliation, it’s easy to agree that Operation Warp Speed is one of the most ambitious scientific endeavors in human history. The result of the operation will change the course of the pandemic, the subsequent economic and societal upheaval it caused, as well as the future course of pharmaceutical development and scientific research. Its success depends on a commitment to safety over speed and scientific integrity over political ambition.

References Center for Biologics Evaluation and Research. Vaccine Product Approval Process. https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/

Figure 2. To distribute millions of COVID-19 vaccines, manufacturers need to produce not only the vaccine itself, but millions of vials and stoppers. Photo credit: "2 ml serum vials" by savard.photo is licensed under CC BY-NC-ND 2.0

vaccine-product-approval-process.

Corum, Jonathan, et al. “Coronavirus Vaccine Tracker.” The New York Times, The New York Times, 10 June 2020, www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html.

million doses of the vaccine (Fact Sheet, 2020). If a vaccine doesn’t make the final cut, there will be many manufactured doses that can never be used. Even with an operational manufacturing plant, there are still other logistical hurdles complicating production. Manufacturers also need millions of glass vials, matching stoppers, and the precise machinery necessary to fill them (Thompson, 2020).

From the Factory to the Frontlines: The Operation Warp Speed Strategy for Distributing a COVID-19 Vaccine. HHS.gov. https://www.hhs.gov/sites/default/files/strategy-for distributing-COVID-19-vaccine.pdf.

Huang, P. (2020, September 22). With Limited COVID-19 Vaccine Doses, Who Would Get Them First? Retrieved October 12, 2020, from https://www.npr.org/sections/ health-shots/2020/09/22/915662174/with-limited-COVID-19-vaccine-doses-whowould-get-it-first

Distribution

Post-production distribution of a vaccine requires cooperation between state health agencies and the federal government. Currently the CDC is collaborating with local, tribal, and state officials in several jurisdictions to create and refine vaccine distribution protocols. California, Florida, Minnesota, North Dakota, and Philadelphia are all pilot jurisdictions, which will create the basic administrative framework for distribution of vaccines and act as a model for other areas (Factory to Frontlines, 2020). To consolidate the distribution of COVID-19 vaccines, the federal government contracted McKesson Corporation, which distributed the H1N1 vaccine in 2009-2010.

McKesson will work under the CDC and DoD to deliver vaccines to their specified locations in the temperature-controlled settings required to maintain them (Factory to Frontlines, 2020). Additionally, Walgreens and CVS are contracted to distribute and administer the vaccine to long-term care facilities (Fact Sheet, 2020).

HHS currently has a vaccine tracking infrastructure that they will use to track and monitor the COVID-19 vaccine supply chain. Currently they are upgrading the system to manage the COVID-19 vaccine distribution in part by adding private, local, state, and federal agencies to the network (Factory to Frontlines, 2020).

Provided logistical infrastructure is ready and efficient, the number of initial doses will not be enough for the entire US population. OWS predicts 10 to 15 million doses will be available at the out-

Lurie, N., Saville, M., Hatchett, R., & Halton, J. (2020). Developing Covid-19 vaccines at pandemic speed. New England Journal of Medicine, 382(21), 1969-1973.

Secretary, H., & Assistant Secretary for Public Affairs (ASPA). (2020, September 24).

Fact Sheet: Explaining Operation Warp Speed. Retrieved October 05, 2020, from https://www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html Singh, K., & Mehta, S. (2016). The clinical development process for a novel preventive vaccine: An overview. Journal of postgraduate medicine, 62(1), 4–11. https://doi. org/10.4103/0022-3859.173187 Thompson, Stuart A. “How Long Will a Vaccine Really Take?” The New York Times, The New York Times, 30 Apr. 2020, www.nytimes.com/interactive/2020/04/30/opinion/coronavirus-COVID-vaccine.html.

UW School of Medicine and Public Health. (2020). UW Health and University of Wisconsin School of Medicine and Public Health selected among first clinical sites

EDITORIAL

Phase III

Phase III trials assess the final vaccine formulation in thousands of research participants. Often this experiment takes place in the form of a double-blind RCT, meaning neither the research participant nor the doctor knows if the patient received the placebo or actual vaccine. RCTs minimize bias, control variables, and provide the best data for determining the efficacy of the final formulation.

Researchers study how effective the vaccine is by measuring the percentage of individuals affected by the pathogen in the vaccine and placebo groups. They apply statistical tests to determine if those who received the vaccine were better protected from the pathogen than those who received the placebo. If this is true, the vaccine is considered a success. Like Phase I and Phase II, more than one study is often required to determine the vaccine’s effect on different populations. The location and specific population studied in Phase III is carefully considered, and researchers draw from a vast amount of epidemiological data to ensure the data accurately reflects the efficacy of the final formulation. If the Phase III trial demonstrates the vaccine is effective and safe, then developers can apply for license to move forward with commercial development (Singh, 2016). During the COVID-19 pandemic, the vaccine developer will likely apply for an emergency use authorization from the FDA and then move into further approval steps (Corum, Jonathan, et al, 2020).

Following the licensure of a vaccine, regulatory bodies such as the FDA continue to oversee its production and monitor safety and efficacy. This regulation takes many forms, but usually incudes manufacturing site inspections and the continuous collection of more data as the vaccine’s use becomes widespread (Center for Biologics Evaluation and Research).

H1N1 vaccine was not immediately available at the height of the H1N1 epidemic, it has since been incorporated into seasonal flu vaccines (Lurie, 2020). In fact, scientists were able to circumvent some regulatory steps necessary for a SARS-CoV-19 vaccine by licensing the H1N1 vaccine under an influenza strain change. When an epidemic ends, such as with SARS and Zika, regulators tend to cut short vaccine development and reallocate their funding and research energy elsewhere (Lurie, 2020). Such an end to the current pandemic is unlikely.

In non-pandemic conditions, developing a vaccine in the United States often stretches years and even decades. In the past decade, only about 15 vaccines have been approved for use in the United States and only one in 15 vaccines make it through Phase II trials (Norman, 2020). This backdrop makes the Operation Warp Speed Vaccine Initiative uniquely ambitious.

in the U.S. to test new COVID-19 vaccine. https://www.med.wisc.edu/news-andevents/2020/august/uw-uw-health-selected-for-COVID-19-vaccine-trials/

Vaccine Types. (n.d.). Retrieved October 05, 2020, from https://www.niaid.nih.gov/ research/vaccine-types

Van Norman G. A. (2020). Warp Speed Operations in the COVID-19 Pandemic: Moving Too Quickly?. JACC. Basic to translational science, 5(7), 730–734. https://doi. org/10.1016/j.jacbts.2020.06.001

Weiland, N., & Sanger, D. E. (2020, June 3). Trump Administration Selects Five Coro-

navirus Vaccine Candidates as Finalists. The New York Times. https://www.nytimes. com/2020/06/03/us/politics/coronavirus-vaccine-trump-moderna.html.

Zepp, F. (2010). Principles of vaccine design—lessons from nature. Vaccine, 28, C14-C24

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PIXELS

Devil's Lake | October 21, 2020

where science and art collide

Full Moon | June 5, 2020

Moss Growth on Boulder | October 21, 2020

Fall Leaves | November 7, 2020

PHOTO SUBMISSIONS

Ashley Harris

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Discoveries in the Field of Brain Network Analysis..32 Humans do not understand the full capacity of their brain. Recently, scientists have learned many aspects about the brain (its function, which parts of the brain perform which functions, etc.) But what scientists still do not know is how different parts of the brain communicate. What pathways or networks do these communication travel on and how are similar communications differentiated? Recently, scientists have been trying to answer that question by creating a valid model of the brain network to then analyze.

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Discoveries in the Field of Brain Network Analysis Justin Magnus

Humans do not understand the full capacity of their brain. Recently, scientists have learned many aspects about the brain (its function, which parts of the brain perform which functions, etc.) But what scientists still do not know is how different parts of the brain communicate.

What pathways or networks do these communication travel on and how are similar communications differentiated? Recently, scientists have been trying to answer that question by creating a valid model of the brain network to then analyze.

The Watts-Strogatz (WS) small-world model is the first working model for brain network analysis. It is useful for generating some small-world networks. However, it cannot generate all small-world networks in the human brain. Therefore, scientists needed to come up with new models (e.g., hierarchical modular network models) to think of how information travels in human brain networks. The hierarchical modular network model represents large-world networks with a finite topological dimension (Kaiser et al., 2007). A topological dimension is the geometric properties and spatial relations of that object, in this case a brain network. These topological dimensions offer unique dimensions of brain network analysis for scientists that use the unweighted (binary) graphing method and the weighted graphing method to graph human brain networks.

Historically, scientists used the unweighted graphing method because of its simplicity. However, more recent tract-tracing research experiments use the weighted graphing method because it retains the sophisticated data on brain connectivity, which is the more biologically relevant information (Bassett, 2017). Currently, scientists make discoveries using the weighted graphing method in brain network research. For example, scientists have proven that brain network research can use TRT reliable weighted network metrics derived from fNIRS to graph brain connectivity (Wang et al., 2019). Thus, allowing scientists to use the weighted graphing method as a reliable way to quantitatively characterize the functional architecture of the human brain network.

New discoveries are reshaping scientific beliefs in the field of brain network analysis. In order to continue making discoveries (new models or ways to map

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brain networks), there needs to be a literary review on the field’s past, present, and future discoveries. This is a literary review on the past, present, and future developments in the field of brain network analysis. I will begin by talking about the first model of brain networks, Watts-Strogatz small world model, the past development.

Then I will talk about how scientists expanded the Watts and Strogatz model to create unweighted and weighted graphs of brain networks, the present development. Finally, I will talk about the scientific uses for unweighted and weighted graphs of brain networks, the future development.

INTRODUCTION:

In 1967, Milgram’s social network experiment demonstrated that any individual is “separated by no more than six degrees of freedom from any other individual in a geographically distributed social network” (Milgram, 1967; Figure 1). This experiment demonstrated that any person can be “related” to a random person somewhere else by six people or less. For example, the Milgram social network experiment demonstrated that if a person in California wanted to send a letter to someone in New York, by sending the letter to people you know, it would take six people or less to get that letter from California to New York. Nearly 30 years later, Duncan Watts and Steve Strogatz formulated the small-world model based on Milgram’s social network experiment. This model suggests that there are networks in the human brain that are highly clustered but have small characteristic path lengths (Telesford et al., 2011; Watts et al., 1998).

Characteristic path lengths are made up of nodes, edges, and path lengths. A node is a computational unit that has an input function and an output function. Nodes are connected by edges. The minimum number of edges to go from one node to another is a path length. The average shortest path length between all pairs of nodes is called the characteristic path length. These characteristics allow the human brain to more efficiently send information from a starting node to an ending node, because of the smaller characteristic path length of a small-world network compared with a regular network. The brain needs a small-world architecture intermediate between regular and random networks because regular networks

THE TOPOLOGY OF UNWEIGHTED GRAPHS AND ITS LIMITATIONS:

The unweighted graph represents a simplified approach to brain network analysis. Even though it is simple and does not retain as much biologically relevant information as weighted graphs, historically it was preferred in neuroimaging because limits the signal-to-noise ratio in the data (Achard et al., 2006). Unweighted graphs are constructed by thresholding a correlation coefficient between regions of two nodes (van Wijk et al., 2010). A small-worldness scalar is then determined by the unweighted graphs, to determine if the brain network has small-world characteristics (Figure 5). Unweighted graph models are useful for determining if the brain network has small-world characteristics, but it has its limitations because it fails to record the amount of the extraordinary range of connectivity weights in tract-tracing data (Ercsey-Ravasz et al., 2013). For example, modern neuroscience has focused on understanding the connectiv-

ity of the cerebral cortex. The cortico-cortical pathways vary widely in connection strength and there is very little data available on quantitative connectivity (Markov et al., 2014). In order to further analyze the cortico-cortical pathways, a weighted graph is needed.

THE TOPOLOGY OF WEIGHTED GRAPHS AND ITS ADVANTAGES:

For future scientific experiments using neuroimaging data (e.g., tract-tracing data and functional MRI), weighted graphs are the preferred method of brain network analysis. (Bassett et al., 2017). Weighted graphs are different from unweighted graphs because they consist of a mathematical equation that determines a brain network’s small-world characteristics estimates, simulates the topological properties of weighted networks, and studies the geometry of the graph it produces (Figure 6). A graph with strongly weighted connections spans the shortest physical distance between cortical areas and graph with weakly weighted connections spans the longest physical distance between cortical areas (Bassett et al., 2017; Ercsey-Ravasz et al., 2013; Klimm et al., 2014; Rubinov et al., 2015). The combination of weight and distance of connections is important for understanding large-scale temporal dynamics (Markov et al., 2014). Current research on the cortico-cortical pathways revealed that weakly weighted connections make an important contribution to the specificity of the cortical network (Markov et al., 2013).

Weakly weighted connections are thought to play a role in imagery integration, multisensory integration, and communication via coordinating oscillatory activity (Markov et al., 2013). Therefore, determining such areas of weakly weighted connections is important because it sheds new light on the cortico-cortical pathways. For example, in order to understand how the structural connectivity of the cerebral cortex relates to its function, scientists need to fully embrace and understand its large-scale connectivity using a weighted graphing method (Markov et al., 2013). Once scientists understand how the connectivity relates to its function, scientists use weighted graphs to analyze the brain network of an individual.

USES FOR BRAIN NETWORK ANALYSIS:

Diffusion MRI, functional MRI and tract-tracing experiments use weighted graphs to analyze brain networks. A review article in 2013 analyzed the human connectome with data from diffusion MRI and functional MRI data. Fornito noted that despite the popularity and simplicity of analyzing unweighted graphs, weighted graphing methods are better for diffusion MRI and functional MRI data because brain network dynamics are an intrinsically weighted system (Fornito et al., 2013).

The weighted graphing method can estimate axonal trajectories and characterize diverse dynamic properties of brain networks more accurately than the unweighted graphing method, but further experiments needed to be done to determine if the weighted graphing JUST VOL VI // ISSUE I // FALL 2020

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have a large characteristic path length and random networks have a higher likelihood of neurological disorders (Figure 2).

The WS model is a graph displaying the smallworld properties and high clustering nodes of a brain network, which makes it a useful model for brain network analysis. But it has its limitations. In 2011, Telesford and Joyce proposed a new small-world metric, w (omega). w compares the clustering of the network to that of an equivalent lattice network to determine the characteristics of the network (Figure 3). A lattice network is an arrangement of nodes, normally a rectangle, that offers increased flexibility to brain networks with a variety of responses achievable. Can distinguish true small-world networks from those that are more closely aligned with random or lattice structures (Betzel et al., 2017; Telesford et al., 2011). This new metric allows scientists to study the unique topological properties of brain networks (Figure 4). Forms the basis for the hierarchical modular network theory, which states that within each module there will be a set of sub-modules. A module is defined as a subset of nodes with high within-module connectivity and low inter-module connectivity (Meunier et al., 2010). Hierarchical modular network models are different from WS small-world network model because the WS model is not modular and hierarchical modular networks can also include large-world networks [e.g., lattice networks] with a finite topological dimension (Meunier et al., 2010).

The topological properties of brain networks are a recent discovery that scientists are trying to understand – so far, scientists have determined two ways to graph the topological properties of brain networks, unweighted [binary] graphs and weighted graphs. It is important to understand both graphs because together they could provide an important analysis of brain networks, and by analyzing brain networks, scientists could one day understand the topology and functional value of the strong and weak links between areas of the mammalian cortex (Bassett, 2017).

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J produced reliable results for brain network research (Fornito et al., 2013). In 2019, scientists conducted an experiment to quantitatively characterize function architecture of the human brain network using resting-state fNIRS imaging data (Wang et al., 2019). The goal of the experiment was to determine if the weighted brain network model is test-retest (TRT) reliable for brain network research. TRT reliability indicates the internal validity of the weighted brain network model by measuring its consistency. If the weighted brain network model is determined to be consistent by the TRT analysis, then brain network research will have a metric to analyze the architecture of the human brain network. Figure 7 illustrates that almost all brain network model metrics exhibit high reliability through most of the thresholds. Therefore, brain network research can use weighted network metrics derived from fNIRS (Wang et al., 2019). This breakthrough demonstrates that brain network analysis has advanced a lot since the Milgram social network experiment.

In conclusion, Milgram’s social network experiment, which demonstrates connectedness of individuals in a geographically distributed social network got the scientific community to think of ways in which information travels in human brain networks. The first scientists to create a working model of human brain networks were Duncan Watts and Steven Strogatz. Their WS small-world model was a great starting point for brain network analysis. One problem with the WS small-world model is that it is not a biologically plausible generative model for brain networks. The human brain network follows more of a hierarchical modular network because of small-world characteristics and its ability to model large-world networks with a finite topological dimension (Kaiser et al., 2007).

The hierarchically modular network models greater robustness, adaptivity, and evolvability of network function, which allows scientists to notice distant connections that may have been missed in other studies (Meunier et al., 2010). Therefore, some network areas are harder to access than others due to the distance of the connections. The unweighted graphing method misses some of these more distant connections because it fails to record an extraordinary range of connectivity weights.

On the other hand, the weighted graphing method accounts for the combination of weight and distance of connections and records an extraordinary range of connectivity weights. Therefore, the weighted graphing method is important for understanding the unique topological dimensions of brain network analysis. Recently, scientists have proved that weighted network metrics derived from fNIRS are TRT reliable and can be used for brain network research (Wang et al., 2019). This finding demonstrates that the weighted graphing method is both important and reliable for experiments aimed at quantitatively characterizing the functional architecture of the human brain network.

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JM would like to thank Professor Yuri Saalmann for providing feedback for this paper.

REFERENCES: Achard S., Salvador R., Whitcher B., Suckling J., Bullmore E. 2006. A resilient, low-frequency, small-world human brain functional network with highly connected association cortical hubs. J Neurosci 26(1):63– 72.

Bassett, D.S., Bullmore, E.T. 2017. “Small-World Brain Networks Revisited.” The Neuroscientist: a review journal bringing neurobiology, neurology and psychiatry vol. 23,5: 499-516.

Betzel, R.F., Avena-Koenigsberger, A., Goni, J., He, J., de Reus, M., Griffa. A., Vertes, P., Misic, B., Thiran, J.P., Hagmann, P., van den Heuvel, M., Zuo, X., Bullmore, E.T., Sporns, O. 2016. “Generative models of the human connectome.” NeuroImage vol. 124,Pt A: 1054-1064.

Ercsey-Ravasz M., Markov N.T., Lamy C., Van Essen D.C., Knoblauch K., Toroczkai Z., Kennedy, H. 2013. “A predictive network model of cerebral cortical connectivity based on a distance rule.” Neuron. 80(1):184–97.

Fornito, A., Zalesky, A., Breakspear, M. 2013. “Graph analysis of the human connectome: Promise, progress, and pitfalls.” NeuroImage 80(C), 426– 444.

and hierarchically modular organization of brain networks. Front. Neurosci. 4:200.

Milgram, S. 1967. “The small world problem.” Psychol Today 2:60–7.

Rubinov, M., Ypma, R., Watson, C., Bullmore, E.T. 2015.

“Wiring cost and topological participation of the mouse brain connectome.” Proc Natl Acad Sci USA 112(32):10032–7.

Telesford, Q.K., Joyce, K.E., Hayasaka, S., Burdette, J.H., Laurienti, P.J. 2011. “The ubiquity of small-world networks.” Brain connectivity vol. 1,5: 367-75. van Wijk B.C., Stam C.J., Daffertshofer A. 2010. “Comparing brain networks of different size and connectivity density using graph theory.” PLoS One 5(10).

Wang, M., Yuan, Z., Niu, H. 2019. “Reliability evaluation on weighted graph metrics of fNIRS brain networks.” Quantitative imaging in medicine and surgery vol. 9,5: 832-841.

Watts, D., Strogatz, S. 1998. Collective dynamics of ‘smallworld’ networks. Nature 393, 440– 442.

Humphries, M.D., Gurney, K., Prescott, T.J. 2006. “The brainstem reticular formation is a smallworld, not scale-free, network.” Proc Biol Sci 273(1585):503–11.

Kaiser, M., Gorner, M., Hilgetag, C.C. 2007. “Criticality of spreading dynamics in hierarchical cluster networks without inhibition.” New J Phys. 9:110.

Klimm, F., Bassett, D.S., Carlson, J.M., Mucha, P.J. 2014.

“Resolving structural variability in network models and the brain.” PLoS Comput Biol 10(3).

Markov, N.T., Ercsey-Ravasz, M.M., Ribeiro Gomes, A.R., Lamy, C., Magrou, L., Vezoli, J., Misery, P., et al. 2014. “A weighted and directed interareal connectivity matrix for macaque cerebral cortex.” Cereb Cortex 24(1):17–36.

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CONCLUSION:

ACKNOWLEDGMENTS:

Markov, N.T., Ercsey-Ravasz, M., Lamy, C., Ribeiro Gomes A.R., Magrou, :., Misery, P., Giroud, P., Barone, P., Dehay, C., Toroczkai, Z., Knoblauch, K., Van Essen, D.C., Kennedy, H. 2013. “The role of long-range connections on the specificity of the macaque interareal cortical network” Proc Natl Acad Sci U S A.110(13):5187–5192.

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Figure 1: is an illustration of Milgram’s social networking experiment. This experiment demonstrated that each person is separated by no more than “six degrees of freedom” (Milgram, 1967). This experiment demonstrated that any person can be “related” to a random person somewhere else by six people or less.

Figure 4: Illustrates the difference between the classical WS small-world network (a) and the hierarchical modular network (b). The main difference between the two is that the hierarchical modular networks possess the features of the WS small-world network and can also be large-world networks with a finite topological dimension (Kaiser et al., 2007).

Figure 5: Illustrates a mathematical equation that determines the small-worldness between two nodes in a brain network. w is the path length of the brain graph which is normalized by its values in a comparable random graph and w is the clustering coefficient of the brain graph which is normalized by its values in a comparable random graph (Bassett et al., 2017).

Figure 6: illustrates a mathematical equation that can determines the weighted small-worldness between two nodes in a brain network. The variables are derived as stated in figure 4 except that the geometry of the graph plays a role (Bassett et al., 2017).

Figure 7: illustrates the “TRT reliability of global network metrics as a function of sparsity threshold (Wang et al., 2019). Almost all metrics are shaded the color green or higher, so there is high reliability in those thresholds.

Figure 3: illustrates a mathematical equation that derives w. w is the small-world measurement, L is the characteristic path length, and C is the clustering. This equation compares clustering data to that of an equivalent lattice networks and the path length to that of an equivalent random network. Values of w are restricted to -1 to 1. Positive values indicate that the graph has more random characteristics, negative values indicate that the graph has more regular or lattice-like characteristics, and values close to zero indicates that the graph has small-world characteristics (Telesford et al., 2011).

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Figure 2: illustrates the differences between regular networks, small-world networks, and random networks. Regular networks are made up of nodes that have same number and length of links.

Small-world networks are like regular networks because most nodes have the same number and length of links. However, a small-world network has a few nodes that are linked with nodes farther away to help information reach further places faster. Random networks are made up of nodes with a randomized number and length of links. Watts and Strogatz’s analyzed all these graphs in order to determine which graphs passes information most efficiently. The main results from Watts and Strogatz’s analysis of this figure are that intermediate values of p, small-world network, are highly clustered like a regular graph but have small characteristic path length like a random graph (Watts et al., 1998). Therefore, a small-world network conveys information more efficiently than regular and random networks.

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Pandemics, Politics, and People.............................40 As we edge closer to the end of this year, it’s become quite evident that 2020 will be defined by its tumultuous course and characterized by a flurried blend of polarized politics and the novel coronavirus. In the past, one might have argued that science and politics stem from completely different spheres of thought. Were we not in the midst of a global public health crisis that has impacted every single one of us, this might have been an acceptable perception. However, it’s difficult to deny the growing impact that coronavirus has on politics and the parallel impact politics has on coronavirus, both on a domestic scale as well as globally. The convergence of politics and science in today’s times may very well shape the upcoming U.S presidential election, rendering it increasingly important to examine the implications of global policy on the spread of novel coronavirus and, perhaps more importantly, why it’s problematic that politics has the capacity to mold the public’s perception of coronavirus in the U.S. Both of these ideas imply the importance of distinguishing fact from fiction and science from politics.

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which scientists have coined SARS-CoV-2 (Mayo Clinic, 2020) is its mechanism of spread. Research indicates that the virus is most likely spread through respiratory droplets (Scientific Brief, 2020), however, more recent research also suggests that airborne transmission cannot be ruled out as a means of spread (Li, Qian, Hang, and et al., 2020).

The World Health Organization defines airborne transmission as the spread of infection due to the presence of viral droplets in the air, which can remain infectious over long periods of time and across large distances (World Health Organization, 2020).

COVID-19

Curbing the spread

Pandemics, Politics, and People

By Myra Mohammad

As we edge closer to the end of this year, it’s become quite evident that 2020 will be defined by its tumultuous course and characterized by a flurried blend of polarized politics and the novel coronavirus. In the past, one might have argued that science and politics stem from completely different spheres of thought. Were we not in the midst of a global public health crisis that has impacted every single one of us, this might have been an acceptable perception. However, it’s difficult to deny the growing impact that coronavirus has on politics and the parallel impact politics has on coronavirus, both on a domestic scale as well as globally. The convergence of politics and science 40 JUST VOL VI // ISSUE I // FALL 2020

in today’s times may very well shape the upcoming U.S presidential election, rendering it increasingly important to examine the implications of global policy on the spread of novel coronavirus and, perhaps more importantly, why it’s problematic that politics has the capacity to mold the public’s perception of coronavirus in the U.S. Both of these ideas imply the importance of distinguishing fact from fiction and science from politics.

Despite a shared consensus on the nature of novel coronavirus and subsequent illness, COVID-19, political responses to the outbreak continue to vary greatly around the world. One important aspect of novel coronavirus,

Political tensions

The importance of trust between the government and its citizens can be evidenced not only by nations which have reaped successful results but also by those that continue to struggle with COVID-19. Here in the United States, the total number of deaths due to coronavirus could exceed a staggering 300,000 by the end of 2020 (Quinn, 2020).

Over the past few months, many have wondered why the US, typically perceived as an epicenter of innovation with a wealth of resources at its disposal, has strained to formulate and implement a centralized solution that effectively addresses the widespread nature of SARS-CoV-2. It’s worth noting that confounding factors such as geographical size and population may very well impact the ease with which proposed mitigation measures are implemented, particularly on a broader scale. Unfortunately, we lack a means of precisely determining the magnitude of such variables; even so, while it may seem difficult to justly compare the

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"The desire to return to a normal economy, college experience and restaurant dining is nearly palpable on the socially-distanced streets. But the magic spell to achieve normality is not magic at all, and rather, a vaccine."

Given the ease with which SARS-CoV-2 can spread, it is no surprise that many political leaders have chosen to focus their efforts on curbing the spread of the virus within their states; however, it’s important to note that not all nations have decided to focus on mitigation strategies. Sweden, for example, initially declined to implement lockdown regulations, instead relying on citizens to follow social-distancing guidelines (Erdbrink & Anderson, 2020).

Aside from an attempt to regain a sense of normalcy, this approach may have been tailored to successfully implement herd immunity, which occurs when a large proportion of a certain population becomes immune to a disease, rendering person-to-person spread unlikely (Herd immunity, 2020). Despite an initial spike in coronavirus cases, some believe that Sweden has now contained the virus within their state, which continues to boast dwindling case numbers and a lower death rate than the US (Miltmore, 2020). It remains unclear whether herd immunity is the reason behind the current downward trend in COVID-19 cases, and epidemiologists are unsure of whether to consider Sweden’s course of action a success or a failure, as neighboring nations such as Norway may be at higher risk of an outbreak due to Sweden’s coronavirus policy (Savage, 2020).

Although the success of Sweden’s unusual coronavirus policies remains controversial, it's difficult to argue that New Zealand’s response to the novel coronavirus outbreak has been anything but effective. In startling contrast to Sweden’s deliberate inaction, upon the first signs of community transmission of coronavirus, New Zealand immediately switched from mitigation strategy to elimination strategy (Editors, 2020), which featured robust quarantine facilities in hotels, a COVID-19 tracing app, and strict lockdown management (Peñaloza, 2020). Despite a resurgence of cases in Auckland a few months prior (Albeck-ripka, 2020), recent case numbers remain in the single digits (COVID-19, 2020), and the risk of contracting the virus in New Zealand is relatively low (COVID-19 in New Zealand, 2020). New Zealand’s success in this matter is unequivocal and proves that while it may be difficult to shut the virus down completely, it is by no means impossible to do so. It is worth noting that Prime Minister Jacinda Ardern has been commended for her swift and thorough action by epidemiologists and citizens alike, which will likely aid her in New Zealand’s upcoming general election (Menon, 2020).

One reason why New Zealand is particularly fascinating is because it exemplifies so clearly how effective policymaking and prompt political action can alleviate a crisis that is otherwise overwhelming in enormity and severity. As other nations face rising coronavirus cases and harsh economic decline, New Zealand has successfully restored the nation to a semblance of what it was in preCOVID times. It’s an achievement that cannot and should not be undermined, though it does beg the question: why is it so difficult for other nations across the globe to achieve similar levels of success and stability?

It’s unlikely that the sole differentiating factor is mitigation strategies, which are relatively standardized across the board. Frequent hand-washing, social distancing, and wearing face-coverings over the nose and mouth areas are recommended by international organizations for countries impacted by the coronavirus outbreak (Advice for the public, 2020). There may be outliers in this regard, but the vast majority of nations have likely attempted to standardize the aforementioned guidelines in one form or another. In the case of New Zealand, arguably the latest gold-standard for coronavirus suppression, effective policymaking appears to have strongly contributed to the nation’s success. Although Prime Minister Ardern’s role in governmental leadership has already been well-established, it’s important to consider the citizens' actions as well. One study indicated that New Zealanders possessed a very high level of knowledge of hygiene practices, the spread of the virus, and common myths about the virus, and were actively social-distancing (Roy, 2020). While citizens in New Zealand actively engaged in mitigation strategies recommended by the government, Prime Minister Ardern simultaneously established a formidable and rigorous system of inhibition, which featured restricted travel and strict lockdown protocols. Instead of opposing governmental action, citizens worked with political leaders to curb the spread of the virus, which may be one of the primary reasons why New Zealand is so successful compared to other countries.

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compromising our reliance on observation, evidence, and reason, but we also risk exacerbating wide-scale issues such as novel coronavirus.

Factors of spread

In examining international policy pertinent to the containment of novel coronavirus, it becomes clear that the effectiveness of mitigation strategy relies on a plethora of factors. The widespread nature of the virus and subsequent difficulty in effectively implementing mitigation strategies have inherently exposed systemic inadequacies of many governmental bodies around the world. Without experiencing firsthand the magnitude of a crisis like this one, it might be fairly easy to ensure that, in the case of a global pandemic, one’s government and political leaders would be prepared and well-equipped. However, many nations lack fundamental infrastructure and resources required to effectively address the issue. Italy, for example, has experienced such an enormous influx of COVID patients, that healthcare facilities such as hospitals are overwhelmed and at full capacity (Horowitz, 2020). Other countries might struggle to concur on the best course of action, resulting in splintered opinion on the nature of the virus amongst the populate. While it might feel like there is little we can do as individuals to solve an issue of such magnitude, we can each contribute to alleviating the crisis.

Political involvement might be one of the most impactful ways we can voice our concerns on issues like coronavirus, both on a grassroots level as well as on a broader political scale. In addition, following protocols outlined by health professionals is a simple way we can help protect ourselves, our loved ones, and our communities, ensuring we don’t exacerbate the spread of novel coronavirus. Indeed, the most significant takeaway from the global response to this pandemic is arguably the power of personal action within the scope of a dangerously divisive society.

References Advice for the public on COVID-19. (2020). WHO. [Retrieved October 11, 2020], from https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public Albeck-ripka, L. (2020, October 07). New Zealand Stamps Out the Virus. For a Second Time. The New York Times. [Retrieved October 10, 2020], from https:// www.nytimes.com/2020/10/07/world/australia/new-zealand-coronavirus.html COVID-19: Current cases. (2020). New Zealand Ministry of Health. [Retrieved October 11, 2020], from https://www.health.govt.nz/our-work/diseases-and-conditions/covid-19-novel-coronavirus/covid-19-current-situation/covid-19-current-cases COVID-19 in New Zealand - Watch - Level 1, Practice Usual Precautions - Travel Health Notices.

(2020). Centers for Disease Control. [Retrieved October 11, 2020], from https://wwwnc.cdc.gov/travel/notices/watch/ coronavirus-new-zealand Devlin, K., & Connaughton, A. (2020, September 23).

COVID-19 Response Approved by Most in 14 Nations with Advanced Economies. PEW Research. [Retrieved October 11, 2020], from https://www.pewresearch. org/global/2020/08/27/most-approve-of-national-responseto-covid-19-in-14-advanced-economies/ Dustin, P. and Calvillo, B. (2020). Political Ideology Predicts Perceptions of the Threat of COVID-19 (and Susceptibility to Fake News About It) - Dustin P. Calvillo, Bryan J. Ross, Ryan J. B. Garcia, Thomas J. Smelter, Abraham M. Rutchick, 2020. [Retrieved October 11, 2020], from https://journals.sagepub.com/doi/ full/10.1177/1948550620940539 Editors, T., J. H. Beigel and Others, & Group, T. (2020, October 08). Successful Elimination of Covid-19 Transmission in New Zealand: NEJM. doi/full/10.1056/NEJMc2025203 Erdbrink, T. and Anderson, C. (2020, April 28). 'Life Has to Go On': How Sweden Has Faced the Virus Without a Lockdown. The New York Times. [Retrieved October 10, 2020], from https://www.nytimes.com/2020/04/28/world/europe/sweden-coronavirus-herd-immunity.html Herd immunity and COVID-19 (coronavirus): What you need to know. (2020, June 06). Mayo Clinic.

[Retrieved October 10, 2020], from https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/herd-immunity-and-coronavirus/art-20486808 Holm, E. J. (2020, January). The Impact of Political Ideology on Concern and Behavior During COVID-19. SSRN. doi:10.2139/ssrn.3573224 Horowitz, J. (2020, March 12). Italy's Health Care System Groans Under Coronavirus - a Warning to the World. The New York Times. [Retrieved October 22, 2020], from https://www.nytimes.com/2020/03/12/world/europe/12italy-coronavirus-health-care.html Li, Y., Qian, H., Hang, J., Chen, X., Hong, L., Liang, P., et al.

(2020, April 22). Evidence for probable aerosol transmission of SARS-CoV-2 in a poorly ventilated restaurant. medRxiv. doi.org/10.1101/2020.04.16.20067728 Mayo Clinic. (2020, September 10). COVID-19 (coronavirus) vaccine: Get the facts. Retrieved from https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-vaccine/art-20484859 Menon, P. (2020, October 09). Ardern maintains lead in NZ election poll. Financial Review. [Retrieved October 11, 2020], from https://www.afr.com/world/pacific/ ardern-maintains-lead-in-nz-election-poll-20201009-p563or Miltimore, J. (2020, September 04). Sweden Now Has a Lower COVID-19 Death Rate Than the US. Here's Why It Matters. Foundation for Economic Education. [Retrieved October 10, 2020], from https://fee.org/articles/sweden-now-has-a-lower-covid-19-death-rate-than-theus-here-s-why-it-matters/ Peñaloza, M. (2020, October 07). New Zealand Declares Victory Over Coronavirus Again, Lifts Auckland Restrictions. NPR. [Retrieved October 10, 2020], from https://www.npr.org/sections/coronavirus-live-updates/2020/10/07/921171807/new-zealand-declares-victory-over-coronavirus-again-lifts-auckland-restrictions Quinn, M. (2020, August 09). Gottlieb says U.S. could reach

300,000 COVID deaths by end of the year.

CBS News. [Retrieved October 11, 2020], from https://www. cbsnews.com/news/scott-gottlieb-coronavirus-300000covid-deaths-by-end-of-2020-face-the-nation/ Roy, E. (2020, July 23). New Zealand beat Covid-19 by trusting leaders and following advice – study.

The Guardian. [Retrieved October 11, 2020], from https:// www.theguardian.com/world/2020/jul/24/new-zealandbeat-covid-19-by-trusting-leaders-and-following-advicestudy Republicans, Democrats Move Even Further Apart in Coronavirus Concerns. (2020, August 28).

PEW Research. [Retrieved October 11, 2020], from https://www.pewresearch.org/politics/2020/06/25/republicans-democrats-move-even-further-apart-in-coronavirus-concerns/ Savage, M. (2020, July 23). Did Sweden's coronavirus strategy succeed or fail? BBC News. [Retrieved October 10, 2020], from https://www.bbc.com/news/ world-europe-53498133 Scientific Brief: SARS-CoV-2 and Potential Airborne Transmission. (2020, October 5). Centers for Disease Control. [Retrieved October 10, 2020], from https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-brief-sars-cov-2.html Weible, C., Nohrstedt, D., Cairney, P., Carter, D., Crow, D., Durnová, A., et al. (2020, April 18).

COVID-19 and the policy sciences: Initial reactions and perspectives. Policy Science. doi:10.1007/s11077-020-093814 World Health Organization. (2020, July 9). Transmission of SARS-CoV-2: Implications for infection prevention precautions. WHO. [Retrieved October 11, 2020], from https://www.who.int/news-room/commentaries/detail/transmission-of-sars-cov-2-implications-for-infection-prevention-precautions

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current state of the US to that of smaller, better isolated, and less populated nations, there are still a multitude of differentiating factors we can evaluate.

In the US, for example, where coronavirus generally impacts political response, politics also appears to be shaping the public’s perception of coronavirus, particularly in regards to whether the virus is a viable threat or not (Dustin & Cavillo, 2020). Issues such as risk of hospitalization, necessity of additional aid, importance of mask-wearing, and required government intervention have all sparked sharp disagreement between two major political parties, the Republicans and the Democrats (Republicans, Democrats, 2020). These disagreements are significant for a number of reasons. For one, in a generalized sense, they represent that instead of acting as a unifying force within the political sphere as past crises have, coronavirus has fortified party lines and strengthened political division. In fact, while research indicates varied responses from other nations on the question of whether coronavirus has helped unite people, Americans stand out in their resounding belief that the country is more divided than it was prior to the coronavirus outbreak (Devlin & Connaughton, 2020).

These kinds of divisions make it increasingly difficult to address such a focal issue on a wide scale, as they inherently hinder the capacity of a nation to agree on measures that should be taken and interventions that need to be implemented. Marred by political disorder and widespread confusion, the relationship between the US government and its citizens is tenuous at best, the ramifications of which are undeniably far-reaching.

In addition to revealing growing tensions between political parties, the US has inherently exemplified how politics has the capacity to shape one’s views on coronavirus. Not only can political ideology be used to predict how one measures the threat of coronavirus (Dustin & Cavillo, 2020), but research also indicates that political ideology can impact consequent behavior in response to coronavirus (Holm, 2020), which is deeply troubling for several reasons. While one’s opinions are rendered malleable by thoughts and experiences, science draws from an unfaltering set of principles that center around evidence-based reasoning, a characteristic which contributes to its durability and consequent significance. In contrast, politics can often be characterized by how an issue is framed and the evocation of emotion (Weible, Nohrstedt, Cairney, and et al., 2020). One could argue that politics is a polarizing topic in the vast majority of places and that may be true; however, as evidenced by New Zealand, citizens tend to agree on pressing issues like the current pandemic regardless of political stance. In the US, because politics and coronavirus have become so fiercely intertwined, one might struggle to distinguish where one ends and the other begins, blurring the line between opinion and fact. The inability to distinguish one from the other risks diminishing the credibility of scientific evidence, as one might fallaciously tie such evidence to certain political ideals. In an effort to align with a specific set of ideals, one could easily undermine the gravity of an issue like coronavirus, enabling further spread.

Conclusively, by establishing this infallible bond between political ideals and scientific evidence, not only do we risk

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The Journal of Undergraduate Science and Technology (JUST) is an interdisciplinary journal for the publication and dissemination of undergraduate research conducted at the University of Wisconsin-Madison.

Encompassing all areas of research in science and technology, JUST aims to provide an open-access platform for undergraduates to share their research with the university and the Madison community at large.