House Tax Bill Could Lead to Significant Tax Increase for UNC Grad Students

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The current IRS 1040 income tax form.

Last Thursday, the House of Representatives passed a version of the tax reform bill that, if made into law, could lead to a massive tax increase for many US graduate students.

The cause of this would be the removal of section 117(d)(5) from the tax code. This section establishes that any reduction to university tuition, granted in exchange for work, cannot be taxed.

Many graduate students work as teachers and researchers at their universities, and in exchange receive moderate stipends and have their tuition costs covered by waivers. The removal of section 117(d)(5) would mean that the value of these tuition waivers would be considered part of a student’s taxable income.

Depending on course load, a graduate student enrolled at UNC’s School of Medicine, is  charged from around $8,000 to $34,000 in out-of-state tuition. These numbers vary between different graduate programs at UNC, but generally fall within this range. That means a UNC graduate student in the life-sciences, receiving a $30,000 stipend, could see their taxable income increase to more than $60,000, without taking home any extra money.  

How much your taxes would increase would depend on factors like your residency status, credit hours, and the stipend value. But even for students with relatively low tuition costs, the increase could be several thousand dollars annually, adding significant financial strain for many students who are already scraping by. The effect would be even worse at institutions like MIT and Harvard, where graduate tuition can be more than $50,000.

Graduate students would not be the only ones affected. University employees are the other major group that benefit from tax-exempt tuition waivers, and are often able to send their children to school at greatly reduced costs. For many, that means access to education that would otherwise be prohibitively expensive.

Cutting tuition waiver tax exemption is not the only way the House bill would impact higher education though. The bill would also drop a $2,500 deduction of student loan interest, as well as the tax exempt status for bond financing at private universities.

Unsurprisingly, the House bill has been met with significant concern by US educational institutions as well as students. Erin Rousseau, a graduate student at MIT, wrote a sharp essay for the New York Times on how the House tax reforms may force her to leave school, and the president of Elon University, Leo Lambert, wrote an op-ed piece in the Raleigh News and Observer in opposition. The Association of American Universities has also issued a statement arguing that the proposed reforms would make higher education less accessible for many Americans.

On the other side, arguments have been made that the relevant proposals, particularly the removal of section 117(d)(5), would not be as detrimental to graduate education as many have claimed.

Forbe’s contributor Preston Cooper wrote that colleges could dodge any negative effects by simply reclassifying tuition waivers as scholarships. That change, Cooper argues, would keep tuition assistance protected from being taxed. Whether it’s feasible for public universities like UNC to make this change rapidly enough isn’t clear, but it seems reasonable that universities could make some adjustments to help students.

All that said, it’s important to point out that the Senate version of the tax reform bill, which could be voted on as soon as next week, retains the tax-exempt status of tuition waivers. So, it is still very much undecided whether the reforms affecting higher-ed will actually become law.

Even though the House bill has already passed, the UNC Graduate and Professional Student Federation (GPSF) has urged students to petition their senators to fight the House proposals and to prevent any reforms to tuition waivers from being made into law. Students should also call their state senators, North Carolina Senators Richard Burr and Thom Tillis.

With the Senate potentially voting on their version of the tax bill at the end of the month, the debate over these tax reforms is almost certainly just getting started.

Peer edited by Erika Van Goethem.

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Let’s Talk about Pets!

 Photo: Erin Spencer

Meet Marshmallow, an expert snuggler.

I love my pets. Growing up, I always had animals: fish, hamsters, hermit crabs, and even rats (my mom was particularly happy when those were out of the house). The current menagerie includes two cats, two fish, a bearded dragon, and a horse, and two fish.

Pets provide us joy (how many cat videos have you watched today?) and can even help us live longer. And they’re popular: 63% of American households have pets, resulting in more than 360 million pets in the United States alone. Consequently, pets and pet products account for over $40 billion in spending in the United States every year.

If you’re pet-obsessed (like me!), that probably doesn’t come as a surprise. But what might surprise you is that pets can pose a massive threat to our native ecosystems.

Even when people buy animals with the best intentions, a lot of things can change throughout the course of pet ownership. Maybe they realize their hubby is allergic to cats, or that teeny baby turtle outgrew his aquarium. Regardless of the reason, many pet owners will ultimately face a difficult decision: what do you do with a pet you can no longer care for?

Releasing pets into the wild may be considered a “humane” response by unknowing owners (thanks a lot Finding Nemo), but this is problematic for a number of reasons. First, a significant change in environment will likely be stressful for the pet and could lead to death. Second, they might be carrying diseases or pathogens that could spread to native wildlife, which is why even seemingly innocuous actions like flushing a dead fish could be dangerous. Lastly, in the right climate, released pets could establish breeding populations and become invasive.

Photo: Erin Spencer

The lionfish is an invasive species introduced in the Western Atlantic through aquarium releases.

This is more common than you might think. Here are a few examples of released pets becoming invasive pests in the United States:

  • Lionfish: Originally from the Indo-Pacific, these venomous fish are wreaking havoc on native fish populations in the Western Atlantic, Caribbean, and Gulf of Mexico. Considered the “Hoover vacuums of the sea”, lionfish will eat anything up to half their size. Despite being highly invasive, they are still a popular aquarium fish are are sold in the United States.
  • Cats: Your cuddly kittens have a deadly side. Domestic outdoor and feral cats kill a median of 2.4 billion birds and 12.3 billion mammals every year, leading cats to be considered one of the largest human-linked threats to wildlife in the country.
  • Giant African Land Snail: These massive mollusks are one of the world’s largest snails and consume more than 500 types of plants. To top it off, they can damage plaster and stucco structures and can carry a parasitic nematode that causes meningitis in humans.
  • Burmese python:  Reaching up to 23 ft in length, Burmese pythons are some of the largest snakes in the world. Now an invasive species established throughout South Florida, Burmese pythons pose a serious risk to native wildlife and domestic pets. More than 2,000 pythons have been removed from the Everglades National Park since 2002, a figure that likely represents a small fraction of the population.

And the list goes on (check out this site if you want to read more). Thankfully, there are definitive steps that we can take as pet owners to make sure we aren’t contributing to this massive problem.

  1. First and foremost: never, ever release your pets into the wild.
  2. Keep your pet in appropriate housing to minimize chances of escaping.
  3. Properly dispose of materials in your pet’s habitat, including bedding, tank water, terrarium plants, and anything that might carry pathogens or “hitchhikers” from your pet.
  4. Never release live pet food like crickets or feeder fish. Always make sure these animals are kept in secure containers so they cannot escape.
  5. Thoroughly do your research before buying a pet. Ask how care will change as the pet gets older to make sure you’re equipped to take care of the animal throughout its lifetime.
  6. Ask your pet store about their return policy — some stores will take animals back past the normal 30 day return period.

Invasive species are a massive threat to ecosystems and economies worldwide, costing $120 billion in damages each year in the United States alone. We all need to do our part to prevent the next big species invasion by practicing responsible pet ownership.

The environment (and your pets!) will thank you.

Photo: Erin Spencer

Dracarys is perfectly happy in his aquarium, thank you very much.

Peer edited by James Custer.

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A Stimulating Treatment for Drug Addiction

Drug addiction is notoriously difficult to treat. Limited treatment options are available for those suffering from addiction, including behavioral therapy, rehabilitation programs, and medication. However, current drug addiction medications are only approved to treat opioid, tobacco, or alcohol abuse, leaving out many other drugs of abuse,such as cocaine or methamphetamine.

Yet even when patients successfully complete rehab or stick to a medication plan, there is still a risk of relapse. This can often be due to the emergence of drug cravings. For instance, a former alcoholic may see a sign for a bar they used to frequent. That sign can induce feelings of craving for alcohol, even long after the user quits or abstains from drinking. Strong cravings could lead to a relapse and a resumption of the cycle of addiction.  

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No pharmaceutical treatments are currently available for cocaine addiction.

However, a recent discovery may change the way we approach drug addiction treatment. Italian researchers, working alongside the National Institute on Drug Abuse (NIDA), were able to reduce drug cravings and usage in cocaine addicts for the first time using a technique called transcranial magnetic stimulation (TMS).

Long-term use of drugs change how brain cells communicate to each other. Think of a drug addict’s brain cells as speaking in gibberish, or unable to speak at all. Important messages aren’t being sent correctly, which contributes to the negative effects of addiction.

In a TMS procedure, researchers place a figure-8-shaped magnetic coil on the patient’s head. When turned on, the coil can send electrical signals into the brain. Importantly, brain cells communicate using electricity, and the “messages” between cells depend on the strength and frequency of these signals. Researchers found that the electrical signals from TMS help change the way brain cells “speak” to each other, getting rid of the gibberish and making cells communicate normally.

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TMS uses a magnetic coil to send electric signals into the brain.

In the case of drug addicts, the electrical signals from the magnetic coil are focused at a brain region called the dorsolateral prefrontal cortex (dlPFC). This is a part of the brain that handles decision making and cognitive ability, and is affected by drugs of abuse. For instance, drug addicts demonstrate lower dlPFC activity compared to non-addicted individuals during cognitive tasks.

Knowing how important this brain region is, researchers performed a study where they stimulated the dlPFC of drug addicts using TMS. They had cocaine addicts undergo either the TMS procedure or take medication (as a control group). They found that the cocaine users who experienced TMS had less cocaine cravings than their control counterparts. Further, the TMS group had more cocaine-free urine samples compared to the control group.

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The dorsolateral prefrontal cortex is affected by drug addiction.

Other studies support these results, focusing specifically on the prefrontal cortex, which appears to be a “sweet spot” for treating drug addiction. For instance, an earlier study found that daily TMS sessions, focused more broadly at the left prefrontal cortex, reduced cocaine craving. A later study honing in on the left dlPFC found similar reduction of craving in cocaine users.

Interestingly, the Italian TMS study was based on a rodent experiment with a very similar design. In this study, researchers allowed rats to develop a cocaine addiction and then stimulated a brain region analogous to the human dlPFC. Amazingly, the rats decreased cocaine seeking behaviors, much like their human counterparts in the TMS study. When this brain region was inhibited, or “turned off”, the rats increased their cocaine seeking.

Despite their promise, these TMS studies are just the beginning. Researchers are still a long way from developing a cure or reliable treatment for drug addiction. Like any new drug or treatment, it will be many years before TMS could be accepted as standard care for drug addicts. However, TMS has been successfully used to help patients in other ways. For instance, it has been used to help treat depression and is often used to help doctors identify damage from strokes, brain injuries, and neurodegenerative diseases. TMS holds a lot of promise and is on the cusp of being a successful drug addiction treatment. It’s only a matter of time before this stimulating idea becomes reality.

Peer edited by Robert Lee and Julia DiFiore.

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Physics Through the Looking Glass

On Christmas Eve 1956, a woman caught the last train to New York in the snow to report experimental results that would alter the landscape of modern physics forever. Although members of the physics community would initially dismiss her results as nonsense, the evidence would soon become incontrovertible, launching many scientific possibilities.

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C. S. Wu working in the lab.

The scientist’s name was Chien-Shiung Wu, and it took her many years of study and perseverance to make this discovery. Starting at a young age, she was quite curious about the natural world. Chien-Shiung Wu’s father, Zhongyi Wu, was an engineer who believed strongly in equal rights for women. He started the first school for girls in his region of China. Chien-Shiung Wu was one of the first girls to obtain a formal education in China. She rapidly outpaced her peers, and proceeded to an all-girls boarding school 50 miles from her home. She continued on to college in Nanjing before traveling across the globe to pursue her graduate degree at University of California, Berkeley, in the US. Not long after her arrival in California, Chien-Shiung learned of the Japanese invasion of China, which affected her family’s hometown. She would not hear from her family for eight long years. After she completed her PhD, she was considered ‘the authority‘ on nuclear fission, according to Robert Oppenheimer. Renowned physicist Enrico Fermi even consulted her for advice on how to sustain a nuclear chain reaction in the making of the atomic bomb.

For decades, physicists had assumed that, there was no way to differentiate left from right according to quantum mechanics. Quantum mechanics is the theoretical underpinning of modern physics that successfully describes the behavior subatomic particles. The assumption that left and right were indistinguishable was known as ‘parity symmetry’. It was naturally appealing, much like symmetries that exist in art, biological organisms, or other natural phenomena, like snowflakes.

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Zoomed-in image of a snowflake. When Mme Wu awaited the train that Christmas Eve, she was surrounded by snowflakes, a reminder of how symmetry is ubiquitous in the natural world. Such symmetries stood in stark contrast to the discovery she was about to announce.

Nonetheless, the idea of this symmetry was called into question at a scientific conference in 1956. Within that same year, Chien-Shiung Wu would demonstrate in her lab at NIST that parity was violated for particular types of decays. In other words, these decay processes did not look the same in a mirror. This discovery was far from Chien-Shiung Wu’s only claim to fame.

Wu made many advancements in beta decay, which is the disintegration of a neutron that results in the emission of an electron and another particle called a neutrino. It was eventually with the beta decay of the element cobalt-60 that she ran her famous parity violation experiment. Using a magnetic field and low temperatures, she was able to achieve the parity violation results that turned the world on its head.

Chien-Shiung Wu did not receive the Nobel Prize, though her two male theorist colleagues did. In spite of this oversight, she obtained recognition in other ways. She was the first female physics instructor at Princeton University and the first female president of the American Physical Society (APS). Her success can be partially attributed to her parent’s encouraging attitude towards women’s education. Fortunately, they survived the Japanese invasion during World War II, with her father engineering the famous Burma Road. C. S. Wu ushered in an entirely new era in which other assumed symmetries would be overturned, helping us to more deeply understand the state of the universe that we see today.

Peer edited by Kaylee Helfrich.

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Cell-based Therapies at UNC using Good Manufacturing Practices, with Dr. Paul Eldridge

T cell-based therapies, or “living drugs” as coined by Dr. Carl June, utilize the potent killing activity of T cells, an arm of the immune system, to target cancers. In the early stages of T cell-based therapy, T cells were isolated from tumors, expanded ex vivo, selected for specific anti-tumor clones, and infused back into the patient. Nowadays, T cell products are genetically modified to express receptors to more specifically target cancers with better persistence in patients. So how are these “living drugs” manufactured?

Here at UNC, a Good Manufacturing Practices (GMP) facility housed off of NC-54 generates all the T cell products used in phase I/phase II clinical trials by the Lineberger Comprehensive Cancer Center. These facilities are regulated by the US Food and Drug Administration under the authority of the Federal Food, Drug, and Cosmetic Act.

 

Image Provided by Dr. Paul Eldridge

Laboratory technicians working hard at UNC GMP.

I spoke with Paul Eldridge, PhD, Director of the UNC Lineberger Advanced Cellular Therapy Facility, to learn more about how GMP facilities work. Dr. Eldridge was recruited in 2014 by the Lineberger Comprehensive Cancer Center, which was interested in starting a cellular immunotherapy program and building a GMP facility. Dr. Eldridge’s personal interests are in chimeric antigen receptor T cells (CAR-Ts) and hematopoietic stem cells, with a focus in cancer immunotherapy.

 

An excerpt of our conversation is below, edited for clarity:

Lee Hong (LH): What products are manufactured at UNC’s GMP facility?

Paul Eldridge (PE): Here at UNC, we focus on advanced research products. The FDA divides cell products into minimal manipulation and more than minimal manipulation. Minimal manipulation essentially does not change the character of the cell, which means you can isolate, purify, or freeze the cells. More than minimal manipulation involves putting cells into tissue culture.

LH: Huh, why is that?

Image Provided by Dr. Paul Eldridge

Tissue culture facility at UNC GMP.

PE: Well, when you put cells into culture, they are dividing, experiencing a different stimulus in the culture medium, and may differentiate into other cell types. In other words, anything that could potentially change the innate nature of the cell is considered more than minimal manipulation. Certainly gene manipulation would be included here as well. How you intend to use the cell products, what the FDA calls “homologous use,” also matters. If the investigator is intending to use the cells in a manner that it is not normally functioning (i.e. non-homologous use), the FDA kicks those products up to a higher regulatory environment and calls them more than minimal manipulation.

LH: So at UNC, are most of the advanced research products you work on derived from peripheral blood?

PE: Yes, we mainly manufacture CAR-T cells from peripheral blood. We are also working with another investigator, Shawn Hingten, who is using skin fibroblasts. Outside of UNC, other investigators are using adipose-derived stem cells or mesenchymal stem cells common in regenerative medicine.

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Schematic of CAR-T cell synthesis using peripheral blood T cells

LH: How is UNC’s GMP facility set up?

PE: The facility is 5,000 square feet, with half of the space as clean room facilities. We have six separate processing rooms, five for patient samples and one with a different air system for virus protection. It’s a ISO-7 environment, meaning we use “bunny suits” and have to re-gown each time we enter or leave a room.

Patient rooms are positive air-pressured to the hallway in order to minimize anything coming back into the room. The air is 80% recirculated. In contrast, the virus room is negative pressure and the air is 100% single-pass filtered with no recirculation.

LH: Oh wow, there are a lot of details involved here.

PE: Yes, part of building a GMP facility is paying attention to construction details. We designed ours for an academic center, which is a different layout than that for pharmaceutical manufacturing.

LH: So how much of what you do in a GMP facility is automated versus manual?

PE: It really depends on where you are in product development. In our facility, we are focused on early phase I trials in which we have not nailed down a manufacturing process so we are pretty manual in most of our applications. Part of what we’re doing is learning how to manufacture the cells we need with minimal effort in a system that is as closed as possible.

As we move to phase II, then we start looking at scaling up due to the need for more cells. This is where bioreactors can be helpful and the steps become more automated. Cell therapy is where drug manufacturing was 75 years ago, in the sense that not much is automated. But nowadays, the technology is continually advancing. Miltenyi is offering a bioreactor called CliniMACS Prodigy that makes it sound as easy as pushing a button.

 Image Credit: Johnny Andrews/UNC-Chapel Hill

Katie McKay, Associate Director for Manufacturing, uses an inverted tissue culture microscope to count cells on a slide while working in the cell culture room at the UNC Lineberger Advanced Cellular Therapeutics Facility on June 16, 2017, in Chapel Hill.

LH: What sort of training and skill sets are needed for someone to work at a GMP facility?

PE: It breaks down into a couple of areas. One is whatever the process requires, in this case usually tissue culture (TC). We do a lot of TC as part of manufacturing cells. Another area is in regulated, quality control testing. We do a lot of characterization analysis on our cell products. We establish release specifications for every product we make so we have to do all the assays before patients can receive them. These assays aren’t necessarily done in the GMP facility, just wherever we can do it most easily.

The important thing is that all the assays need to be performed in a more GMP manner than you might encounter in a basic research lab. Documentation, Standard Operating Procedures (SOPs)…we do everything by SOPs. This is because we need to trace all of our materials, use everything within its expiration date, and keep up with instruments for calibration and maintenance. We also train people on site on whatever they’re doing, document the training, and ensure trainees maintain competency for quality control testing. In other words, we do all the tests you see in a typical research lab but in a more stringent, reproducible, and regulated manner.

Another important skill is learning how to work in a clean environment. Everyone thinks they know how to use a biological safety cabinet (BSC), but there are good ways and bad ways, and there are ways you have to operate when you are trying to minimize the risk of cross contamination. So we do a lot of cleaning, and we have to document everything we do.

In general, I don’t necessarily need someone with PhD credentials but I do need someone who is smart, dedicated, and extremely detail-oriented. We are looking more for personality and attitude than specific qualifications.

Image Credit: Johnny Andrews/UNC-Chapel Hill

Katie McKay, Associate Director for Manufacturing, organizes supplies while working at the UNC Lineberger Advanced Cellular Therapeutics Facility on June 16, 2017, in Chapel Hill.

LH: How are careers and/or skills used at GMP facilities in academic centers different than in pharmaceutical companies?

PE: Well, in an academic center you see everything, and that’s the most enjoyable part of it. We will often break out into more research and development (R&D) work as opposed to hands-on, clean manufacturing work. People float back and forth between what they are comfortable doing. I have people with PhDs and high school degrees working in the facility.

From the industry side of things, a very different set of skills is needed. That’s because by the time you get to phase II/III clinical trials, the process is set and there is no situation where you’ll be making changes. Of course, you still need to have attention to detail and be thorough, but the important aspect is to follow the instructions and nothing else. However, when something doesn’t work, you’ll need enough wherewithal to understand whether it was a process accident or a random occurrence.

LH: Finally, where do you see cell therapy going in the next 25 years?

PE: It’ll become more rote, with more big pharma involved. The current model, as long as we are talking about autologous starting material (i.e. cells from the same patient), is not really scaled up so much as scaled out. There are still individual batches (or lots) made for individual patients. Where will we do this? It’s still not clear where it is economically advantageous to do so.

For example, Novartis has a centralized manufacturing facility [for Kymirah]. That works fine for now, but will Novartis keep up with material demands? It’s not just tissue culture media, they have to make lentiviral vector, and the suppliers right now can turn out product for only 25-30 patients at a time. No one has ever tried making 10,000 personalized products before. Moreover, the FDA requires lentiviral vectors to have a shelf life of couple years so vector suppliers are desperately trying to scale up. We are still in the early wild west stage but it is fascinating.

All pictures provided by Dr. Eldridge.

Peer edited by Justine Grabiec and Erin Langdon.

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Is the GRE a Waste of Money?

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Is the GRE really worth it? Some students are starting think it’s not.

Graduate schools generally utilize previous transcripts, Graduate Record Examination (GRE) scores, personal statements from applicants, and letters of recommendation in order to assess whether candidates are suitably prepared for success in graduate school. However, how much do any of these individual components contribute to the success of a student in graduate school? Multiple published articles argue that there are no methods to precisely measure the success of graduate students, however that hasn’t stopped scientists from trying. In a recent study from the University of North Carolina at Chapel Hill, researchers tackled this question by characterizing success in graduate school as the number of published first-author articles. They then compared this to more traditional parameters that are normally used to determine if students are prepared for graduate school. Students’ grades, GRE scores, and even impressions from admissions interviews with faculty members were each examined and found to have no correlation to success in graduate school. In fact the only predictive indicator of success was found to be letters of recommendation that stated that the student were among the top tier of students.

Although this study was only recently published and has yet to have significant impact on graduate student applications, it is hardly the first study of its kind. A researcher at the University of California at San Francisco (UCSF) utilized data collected from students over the course of a twenty-year period and found that grades and GRE scores were not predictive of the success of students. This UCSF study found that the only indicators of success were whether or not the students had completed a full two years of research prior to graduate school and the subject-specific GRE.

 

Another study conducted at Vanderbilt University in Tennessee essentially found that the only thing that the GRE predicts is the first semester GPA of graduate students. All other markers of success such as passage of qualifying examinations, time to defense, successful completion of a Ph.D., and the likelihood of first-author publications did not correlate with GRE scores. In fact, when the GRE was originally assessed for its ability to predict success of students, the only measurement utilized was to compare GRE scores to the GPA of graduate students.

Image by Lindsay Walton

GRE scores are a better indicator of Race and Gender than of success in Graduate School

So, if the GRE doesn’t predict success in school, what does it actually indicate? Many are questioning the utility of the GRE as a measure that is useful in selecting students. Multiple basic scientists have spoken out against the usefulness of the GRE, and have cited studies that indicate that the GRE is a better predictor of both sex and race than it is an indicator of success in graduate school. As one researcher put it, “The GRE is a proxy for asking ‘Are you rich?’ ‘Are you white?’ ‘Are you male?” For example, some minorities, such as black students typically score 200 points below their white counterparts in spite of being successfully prepared for graduate school. Graduate school is typically a white-predominated educational platform. According to the National Center for Education Statistics, white students represent approximately 64% of the total graduate student population. By continuing to require students to submit GRE scores, schools are eliminating underrepresented minorities as potentially successful candidates, when instead they should be creating additional opportunities to prepare minorities to succeed in graduate school.

 

Most directors of biomedical graduate programs are actually basic scientists. They understand that educational practices should be evidence-based. However, in spite of all this compelling data, few institutions are actually eliminating requirements for extraneous examinations such as the GRE, transcripts, and other requirements. In fact, the University of North Carolina at Chapel Hill and Vanderbilt University researchers, who published the articles on GRE scores not being a predictor of graduate school success, are involved in the admissions process of biomedical programs at their institutions. Nonetheless, these programs still require submission of GRE scores, transcripts, and statements of purpose in spite of the fact that none of these application materials indicated who would thrive in graduate school. So the only question remains: If scientists won’t follow their own advice, how will academic admissions advance in the future?

Update: The author has been contacted by the UNC BBSP admissions office and told that while admissions for the 2018-2019 still requires submission of GRE scores, the admissions committee for the program has been instructed to ignore GRE scores in their consideration of applicants for the upcoming year. Currently the UNC Graduate School requires all programs to request GRE score submission prior to admission. In the future, the UNC BBSP program plans to review the success of the admission process while ignoring the GRE scores and then consider petitioning the UNC Graduate School in order to drop the requirement. 

One of the authors of the UNC paper, and a member of the UNC BBSP team, Dr. Joshua Hall, maintains an active twitter presence and can be found at @jdhallphd. Dr. Hall keeps an active list on his twitter of all the programs that have either dropped or plan to drop the GRE from their admissions process for those interested.

Peer edited by Sam Honeycutt and Kelsey Miller.

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Superbug Super Problem: The Emerging Age of Untreatable Infections

You’ve heard of MRSA. You may even have heard of XDR-TB and CRE. The rise of antibiotic-resistant infections in our communities has been both swift and alarming. But how did these once easily treated infections become the scourges of the healthcare world, and what can we do to stop them?

Antibiotic-resistant bacteria pose an alarming threat to global public health and result in higher mortality, increased medical costs, and longer hospital stays. Disease surveillance shows that infections which were once easily cured, including tuberculosis, pneumonia, gonorrhea, and blood poisoning, are becoming harder and harder to treat. According to the CDC, we are entering the “post-antibiotic era”, where bacterial infections could once again mean a death sentence because no treatment is available. Methicillin-resistant Staphylococcus aureus, or MRSA, kills more Americans every year than emphysema, HIV/AIDS, Parkinson’s disease, and homicide combined. The most serious antibiotic-resistant infections arise in healthcare settings and put particularly vulnerable populations, such as immunosuppressed and elderly patients, at risk. Of the 99,000 Americans per year who die from hospital-acquired infections, the vast majority die due to antibiotic-resistant pathogens.

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Cartoon by Nick D Kim, scienceandink.com. Used by permission

Bacteria become resistant to antibiotics through their inherent biology. Using natural selection and genetic adaptation, they can acquire select genetic mutations that make the bacteria less susceptible to antimicrobial intervention. An example of this could be a bacterium acquiring a mutation that up-regulates the expression of a membrane efflux pump, which is a transport protein that removes toxic substances from the cell. If the gene encoding the transporter is up-regulated or a repressor gene is down-regulated, the pump would then be overexpressed, allowing the bacteria to pump the antibiotic back out of the cell before it can kill the organism. Bacteria can also alter the active sites of antibacterial targets, decreasing the rate with which these drugs can effectively kill the bacteria and requiring higher and higher doses for efficacy. Much of the research on antibiotic resistance is dedicated to better understanding these mutations and developing new and better therapies that can overcome existing resistance mechanisms.

 

While bacteria naturally acquire mutations in their genome that allow them to evolve and survive, the rapid rise of antibiotic resistance in the last few decades has been accelerated by human actions. Antibiotic drugs are overprescribed, used incorrectly, and applied in the wrong context, which expose bacteria to more opportunities to acquire resistance mechanisms. This starts with healthcare professionals, who often prescribe and dispense antibiotics without ensuring they are required. This could include prescribing antibiotics to someone with a viral infection, such as rhinovirus, as well as prescribing a broad spectrum antibiotic without performing the appropriate  tests to confirm which bacterial species they are targeting. The blame is also on patients, not only for seeking out antibiotics as a “cure-all” when it’s not necessarily appropriate, but for poor patient adherence and inappropriate disposal. It’s absolutely imperative that patients follow the advice of a qualified healthcare professional and finish antibiotics as prescribed. If a patient stops dosing early, they may have only cleared out the antibiotic-susceptible bacteria and enabled the stronger, resistant bacteria to thrive in that void. Additionally, if a patient incorrectly disposes of leftover antibiotics, they may end up in the water supply and present new opportunities for bacteria to develop resistance.

 

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Overuse of antibiotics in the agricultural sector also aggravates this problem, because antibiotics are often obtained without veterinary supervision and used without sufficient medical reasons in livestock, crops, and aquaculture, which can spread the drugs into the environment and food supply. These contributing factors to the rise of antibiotic resistance can be mitigated by proper prescriber and patient education and by limiting unnecessary antibiotic use. Policy makers also hold the power to control the spread of resistance by implementing surveillance of treatment failures, strengthening infection prevention, incentivizing antibiotic development in industry, and promoting proper public outreach and education.

 

While the pharmaceutical industry desperately needs to research and develop new antimicrobials to combat the rising number of antibiotic-resistant infections, the onus is also on every member of society to both promote appropriate use of antibiotics as well as ensure safe practices. The World Health Organization has issued guidelines that could help prevent the spread of infection and antibiotic resistance. In addition, World Antibiotic Awareness Week is November 13-19, 2017, and could be used as an opportunity to educate others about the risks associated with antibiotic resistance. These actions could significantly slow the spread and development of resistant infections and encourage the drug development industry to develop new antibiotics, vaccines, and diagnostics that can effectively treat and reduce antibiotic-resistant bacteria.

Peer edited by Sara Musetti 

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Little Farmers in the Animal Kingdom

Think of a farmer. Chances are, an image of an overall-wearing, pitchfork-wielding man just popped into your head. But humans are only one of a surprisingly large group of animals that cultivate their own food.

You might already know about leaf-cutter ants–some 47 species of ants in the New World that meticulously cut fresh vegetation into fragments that look far too big for them to hold. But they somehow manage to carry those leaf and flower cuttings back to their nests. This plant material is then used to feed the fungus that these ants depend on for food. Just like human farmers, the ants regularly plant, cultivate, and harvest their crop. However, rather than wheat or soybeans, the crop is a specific species of fungus. In fact, the relationship between the ant farmers and fungus is so complete that neither can survive without the other: the fungus can no longer  propagate itself without help from the ants, and the ants need the fungus for nutrition. Leaf-cutter ants are an extreme group of farming ants because they are so dependent on their fungal crop for survival, but about 240 ant species (collectively known as the attine ants) practice some form of fungus farming.

https://commons.wikimedia.org/wiki/File:Hitchiking_leafcutter_ant.jpg

A leaf-cutter ant carrying a leaf back to its nest, where the leaf will be used to grow fungi. Image from Wikimedia.

Farming isn’t limited to ants: some species of termites and ambrosia beetles (a type of weevil) are also known to grow fungus for food. These groups demonstrate some of what we think of as the most ‘advanced’ farming. They’re ‘advanced’ because they have evolved many adaptations specific to farming, such as specialized organs or behaviors, and they often can’t survive without farming. Because of this, and because scientists have long-known about the farming practices of these animals, these three groups are the most heavily studied non-human farmers. But focusing on just ants, termites, and beetles overlooks the fact that farming is likely evolutionarily beneficial for many organisms: when food is in short supply, being able to generate your own can be life saving.

Unsurprisingly then, once scientists started looking for evidence of farming in different organisms, they found it in snails, amoebas, and fish, among others. For example, the dusky farmerfish cultivates a specific species of algae. They do so in little ‘gardens,’ which they aggressively defend from other fish. When the farmerfish are experimentally removed from their gardens, all the algae is quickly eaten by other fish. The algae don’t seem to grow outside of these gardens, and the fish rely on this algae as a staple food, making this another relationship where both players need each other to survive.

But not all farming works this way: a different type of farming relationship was described in 2011 between an amoeba and a bacterium. The social amoeba, Dictyostelium discoideum, lives as single-celled organisms that spend their time eating bacteria. When environmental conditions get tough, the individual cells aggregate to form a ‘slug’ that crawls elsewhere more rapidly than the individual amoeba cells could have. Once in a better environment, the slug changes shape again. This time, it turns into a stalked fruiting body that releases spores. Each spore becomes a new single-celled amoeba. Some strains of this amoeba farm their bacteria: instead of eating all the available bacteria, they take some up and incorporate them into their fruiting bodies. When spores are released, the new amoebas are already carrying the bacteria with them, which they then use to seed their new environment with food–just like humans sowing their fields.

https://commons.wikimedia.org/wiki/File:Dictyostelium_discoideum_01.jpg

D. dictyostelium in its stalked form, before releasing spores. These spores may or may not contain bacteria for farming, depending on the D. dictyostelium strain. Image from Wikimedia.

Not all Dictyostelium discoideum individuals demonstrate this farming behavior, which suggests that there could be downsides to farming. In this case, farming may be disadvantageous if the amoebas find themselves in a new environment that is already full of food. If this happens, the farming amoebas would have paid a cost by not eating all of the available food (and growing and reproducing) in their prior environment. In comparison, the non-farming amoebas wouldn’t have paid this same cost because they always eat all the food available to them. Because research on non-human farming has often focused on species that must farm to survive, the costly aspects of this behavior have not been extensively considered.

As scientists continue to explore the diversity of life on Earth, finding and characterizing new farming relationships can continue to give us insight into what this unique behavior can look like, and how it might vary in its evolution.

 

Additional readings:

Ants, termites, beetles: Mueller et al. 2005. The evolution of agriculture in insects. Annual Review of Ecology, Evolution, and Systematics 36:563-95.

Fish and algae: Hata H, Koto M. 2006. A novel obligate cultivation mutualism between damselfish and Polysiphonia algae. Biology Letters 2:593-6.

Amoebas: Brock et al. 2011. Primitive agriculture in a social amoeba. Nature 469:393-8. Brock et al. 2013. Social amoeba farmers carry defensive symbionts to protect and privatize their crops. Nature Communications 4:2385.

Peer edited by Paige Bommarito.

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