Determined young woman climbing up a climbing wall in an indoor climbing gym

More often than not, people come to a point in their academic careers where they hit a wall; some of us just do it more literally than others. What started out as a strange niche sport for people living on the fringe of society has quickly become a fast-growing sport in America. The first indoor climbing gym opened in 1987, and by the end of 2016 there were 414 commercial climbing gyms in America. The growth of the sport is not surprising.

Americans are increasingly interested in outdoor recreation. What does surprise me is the sheer number of researchers embracing the sport. This became immediately apparent when I began my graduate program and started to recognize climbers from the gym around campus. So why is it that rock climbing appeals to so many researchers? I have a few ideas on the matter.

 Scientists love jargon.

We can deny it, and say that we want to become more effective scientific communicators. However, at the end of the day, we enjoy throwing around our acronyms, and showing that we belong in academia by using the esoteric language that science is built on. Now imagine the joy of discovering the whole new body of jargon that rock climbing provides: crimp, dyno, smear. Saying “CRISPR” will elicit the same furrowed brow from your layman.

Scientists love problem solving.

More importantly, rock climbing appeals to the problem-solving nature of a researcher. An indoor climbing wall is covered with specific routes that are marked with tape or color-coded. If you wander over to the bouldering area — where climbing is done without ropes — people will refer to these routes as problems, and they will call a route they can’t climb without falling a project. I’m sure you can already see the parallels. When climbing a project, you will troubleshoot moves on the route until you finally get to the top without falling. It is immensely satisfying to have an experiment finally work after endless rounds of troubleshooting, and that emotion physically manifests in climbing by finally reaching the top of the wall.

Exercise is a natural coping mechanism.

Exercise can ease the emotional struggles that research presents. A recent study of students attending universities in Flanders, Belgium, found that one third of students are at risk of developing a common psychiatric disorder. This underlines the importance of taking steps to promote mental health. Countless studies have shown that exercise can have antidepressant effects. That, combined with the hint of adrenaline that rock climbing provides, is the best recipe for getting over a bad day in the lab.

My hope is that the next time you hit a wall it will be at the gym. Come join the growing army of academic climbers. We have problems you can solve.

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Kyla Britson

Kyla Britson is a Ph.D. candidate in cellular and molecular medicine. She has been playing violin since she was 10. She was in her college’s campus orchestra, and since moving to Baltimore she has been part of the Hunt Valley Symphony. She says playing the violin has always been her artistic break from science.

As I enter the last few weeks of my graduate career, job hunting has become a major aspect of my daily life. The endless job list scouring and cover letter writing can be quite tiring. Fortunately, career fairs can provide a major boost in the job-hunting game by getting students directly in touch with employers who are actively looking for candidates just like you.

We are hiring paper speech bubbles and some paper person under them.

This year marked the third annual Biomedical Ph.D. Career Fair at the Johns Hopkins University School of Medicine. The fair has grown significantly since its inception, and this year included nearly 30 companies who were interested in meeting with Johns Hopkins students and postdoctoral fellows. Representatives from each company set up booths throughout the Turner Concourse area, and some companies also held larger informational sessions. Nearly every company had jobs available that they were actively recruiting to fill. Some companies even held on-site interviews to expedite the hiring process.

By applying in advance, students could be considered for an interview during the career fair, significantly cutting down on travel costs and time. There was also an opportunity for students to submit their resume to the Resume Book, a compilation of resumes that was put together by the career fair organizers and given to all employers who attended the fair.

The diversity of companies represented at the fair was well-matched with the many diverse career paths Ph.D. graduates can pursue. Companies ranged from small biotechnology companies with less than 30 employees to major pharmaceutical companies with thousands of employees and locations all around the world. Additionally, there were consulting firms and government career paths represented.

For Ph.D. students looking to continue to pursue bench research but wanting to leave academia, many of the companies at the career fair offered industry postdoctoral positions or similar positions that provide the same type of mentorship and development that an academic postdoctoral position offers. There were also many staff scientist and research scientist positions being offered. Beyond the world of bench science, career opportunities included managerial positions, engineering roles, policy analysts, technical and medical writing openings and more.

In addition to being a great opportunity for senior graduate students to network with companies and identify job leads, this career fair also serves as an opportunity for more junior students to get a taste for potential career paths. First- and second-year students could be found right alongside the fifth- and sixth-year students talking with recruiters and getting a feel for what it’s like to work at any of these companies. For many graduate students, interactions such as these will help shape their career aspirations as they continue their studies.

At times when funding and career opportunities in academia seem scarce, having alternative career options is essential. Career fairs such as this one provide invaluable networking and learning opportunities for graduate students. Even for those who are not entering the job market quite yet, it is always good to stay up to date with what types of skills companies are looking for in future employees. As for me, fingers crossed that I land the job I fell in love with thanks to this career fair!

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Rebecca Tweedell

Rebecca Tweedell is a fifth-year Ph.D. student in the Cellular and Molecular Medicine program with a strong passion for infectious disease research. In addition to loving anything and everything nerdy and generally uncool, she is an avid runner, rower and random sport participant. Her dream job is to be a Disney princess, singing and performing by day, while writing scientific manuscripts by night.

Have you ever had one of those days when everything and anything goes wrong? Your car won’t start; your roommate used the last of the milk; there is no hot water in your building and, of course, it is pouring outside. Well, in the life of a graduate student, those types of days can start to feel like every day — your experiment didn’t work; your labmate used the last of the reagent you needed, and the microscope is being serviced. This is not to say that entering the lab always feels like opening Pandora’s box; however, graduate students begin most work days acutely aware of the high probability that everything will go wrong.

""With a high likelihood of disappointment perpetually looming over our work, how is it that we, as students, are able to stay motivated for at least five years to complete a Ph.D.? I’ve watched postdoctoral fellows in my lab leave their families overseas to complete papers and projects, and friends leave their homes and friends to follow their labs to different institutions. What is the driving force and where does this motivation come from, when we already know the probability of success is so low?

Of course, I can’t speak for everyone, but as a student entering my third year of graduate school, about halfway to finishing my Ph.D., I am learning that my work and the excitement of engaging in discovery are what drive me. Every day there is the potential for discovery. With each experiment that fails, and with each piece of equipment that is unavailable or broken, I learn new ways to discover. My job is to be creative and innovative — discovery and exploration of new avenues in my field are expected. For me, that provides the motivation to move forward even when experiment after experiment falters.

""Why is science so fragile? Why haven’t we been able to prevent so many of the failures that we experience each day? Scientists are risk takers. Each experiment comes with the bravery that one feels when climbing a mountain or bungee jumping out of an airplane, and the practice of scientific research often requires us to take a leap of faith and pursue our hunches. We believe in the work of our predecessors and colleagues and use their findings to guide our own.

Rarely do we perform “safe” experiments. Instead, we charter into unexplored territory, and therefore it only makes sense that our efforts are met with unforeseen difficulties. The possibility of novelty and unearthing advances in our fields drives us into the lab, stations us at our benches and perpetuates our desire and willingness to try again. Similar to climbing a mountain or bungee jumping from an airplane, it is scary and unsettling at first, but we know that when we finally make it, the struggle and pain will have been well worth it.

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Joelle Dorskind

Joelle Dorskind is a Ph.D. candidate in the Cellular and Molecular Medicine program at Johns Hopkins. When she isn't in lab running experiments, she enjoys reading, playing soccer, running and traveling.

Young woman with laptop computer for homework. Tired hispanic girl and college education. Female student studying and using pc at home getting headacheIf you’re planning to apply to Ph.D. programs this fall, hopefully you’ve — at the very least — thought about starting to write a personal statement. For many students this is one of the most daunting aspects of the application process; however, having a strong personal statement can really set you apart amid a thick stack of applicants and, later on, can give you confidence going into your interviews. Here are some tips from my experience applying to graduate school, with the hope that they can make your own writing process a little easier.

  1. Be aware of the specific personal statement requirements for each school (or program). If you’ve read my previous post on applying to graduate school then this may sound familiar, but it is absolutely crucial that you read the prompt thoroughly, be aware of precisely what it is asking you to write about and make note of any word or length requirements. If your essay fails to address the prompt topic or is longer than the word limit, this may suggest to the admissions committee that you don’t pay attention to detail or follow directions well — first impressions that you don’t want immediately associated with your application.
  1. Tailor your statement to each school you apply to. Although I used much of the same content for all of my personal statements, I had a different iteration for every school that I applied to. This was partially because different schools and programs have different personal statement prompts, length requirements, etc.; however, this is also an opportunity to show specific programs or schools why you are interested in them. Research the faculty at each school, and find a way to tie in how their research fits with the interests you have highlighted elsewhere in your personal statement. This shows the committee that you are interested and engaged in the application process and that you’re already thinking about how your experience and background could add to the science at their school.
  1. Think about a time when you were excited about science. When I first sat down to write my personal statement, I struggled to come up with a cool or exciting moment that I felt captured why I wanted to be a scientist. What I didn’t realize was that for most scientists those moments were something small, or seemingly insignificant: an observation, interesting lecture or experiment that piqued some inherent curiosity that they didn’t know was there. I ultimately chose to open my personal statement with an anecdote about an independent project in a sophomore-level analytical chemistry lab, which was the first time that I collected new data and the first time I understood how exciting and exhilarating scientific inquiry can be. Although the independent project itself wasn’t anything groundbreaking — a partner and I simply measured and compared levels of vitamin C in organic, frozen and nonorganic strawberries — it was the first time I had a gut feeling that scientific pursuit could be not only interesting but fun. Remember that the people reading your application had one of those moments once too (that’s why they’re professors!), and they likely have an eye out for students who have that same excitement and passion.
  1. Set yourself up to succeed in your interviews. Often, your personal statement will be given to the professors who are scheduled to interview you prior to the actual interview. Although you certainly shouldn’t expect every professor to read the whole thing, I would say that more than half of the professors who interviewed me made clear references to my personal statement and/or indicated that they had read or skimmed it. This means that you can use the personal statement to your advantage, based on the content you choose to include or highlight. If you have a unique research experience that you love to talk about (e.g., working in a lab in a different country or using an odd model organism), then you can emphasize this, and if it piques your interviewer’s interest, they may choose to steer the interview conversation toward that topic. Try to stay away from mentioning projects or experiences that you would not be confident discussing in detail with a professor, and keep in mind that anything you talk about in your personal statement becomes fair game for an interviewer to ask about, for better or for worse.
  1. Edit, edit, edit. Send your personal statement to as many people as possible — your mom, undergraduate research advisor, older sibling, a graduate student mentor from your summer research experience — to get feedback. You want it to be interesting and readable (the committees will be reading a lot of essays) but also appropriately technical and scientific. It’s important to get the details right and be confident in the final, finished copy.

Keep in mind that the personal statement is a great opportunity to showcase what it is that makes you special and why you want to pursue science in a graduate-level setting, and it gives the admissions committee one of their first, most intimate impressions of you. If you can convey your excitement about science in an interesting and engaging way, you might just find yourself with a long list of interview offers come December.

Happy writing!

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Emily Fray

Emily is a second-year Ph.D. student in the Biochemistry, Cellular and Molecular Biology Graduate Program. She is passionate about reading and writing about science, learning about infectious diseases, consuming large quantities of caffeine, and studying her personal role model, Louis Pasteur. She hopes to someday combine her loves of English and science to work as an editor for a major journal or textbook company.

The term “doctor” can be traced to its Latin root, docēre, which means “to teach.” And indeed, teaching is ubiquitous in medicine; the residency system that trains physicians is grounded in intensive teaching and learning. Moreover, educating patients about their conditions is a primary objective for every doctor.

Johns Choi lectures to a classroom of high school students

Image courtesy John Choi

But five years ago, I was involved in a different style of education: teaching high school. During that time, I learned invaluable lessons that have also been pertinent to my time in medicine. Below are three takeaways from teaching high school that I continue to keep in mind every day at the hospital. 

Lesson 1: Everyone has a story.

During the second week of my first year teaching, one of my students threw his classmate’s backpack across the room and shattered several graduated cylinders. Before I could react, he stormed out of the classroom. When I eventually caught up to him in the hallway, I learned that he had only been eating the one meal provided by school each day due to financial difficulties at home and was unable to concentrate in class because he was so hungry. It was only after his classmate waved a bag of snacks in front of him mockingly that he lost his temper. In this situation, if I had simply addressed the student’s behavior based off the isolated incident in the classroom instead of taking the time to listen to his story, I would have been unable to address his core issue and actually help him.

Likewise, in the hospital, the quick snapshot of what we learn in a single patient interview rarely tells the entire story. Oftentimes, medical care requires us to go beyond single visits and identify what happens outside of the hospital or clinic to adequately address a patient’s health concerns. It is important to remember that every person has their own circumstances and experiences that inform their current presentation, despite how simple their medical case may seem at first glance.

Lesson 2: Your mindset is important.

When first starting out as a teacher, I saw a flow diagram similar to the one below:

teacher mindsets inform their actions just the way that student mindsets should inform their actions

The concept is simple but incredibly powerful; Your mindset should always inform your actions. Unfortunately, in many professions — including teaching and medicine — it is frighteningly easy for experience to eventually give way to mere force of habit. However, in doing so, the risks of remaining stagnant and losing motivation to commit to your duties can easily follow.

Stanford psychologist Carol Dweck, Ph.D., has written much on the topic of mindset. In several studies, she demonstrated how certain mindsets dramatically impacted performance. Particularly, a growth mindset — in which the person continually seeks to improve — was integral to participants’ long-term success. Similarly, a growth mindset can have tremendous effects on how a physician carries through with their work and views their job. In What Doctors Feel, a book by New York University physician Danielle Ofri, M.D., Ph.D., she discusses how a growth mindset in physicians not only improves patient outcomes but provides the additional benefit of mitigating physician burnout.

Lesson 3: Setting the tone is essential.

In my classroom, we would always spend at least a week at the start of the school year establishing the tone, or culture, of the class. On day one, rather than jumping straight into cells and molecules, we would discuss what the ideal learning environment could look like and brainstorm how we could achieve that together. The goal was to establish an inclusive, engaging and self-motivated learning culture that would permeate everything we did. In doing so, routine tasks that might have otherwise elicited groans became further opportunities for growth.

Similarly, in the hospital, I have seen how the culture of a team informs its practice. When an attending physician rotates onto a service and goes out of the way to establish a safe space, residents are usually able to adjust more quickly and, as a result, work more efficiently. When the senior residents and attending physicians are aware of the impact of developing such a culture, the result is usually a more cohesive and motivated work environment where everyone can invest in the same goals.

Note: John Choi is currently working on a book that would compile stories that highlight the similarities between teaching high school and practicing medicine. If this topic interests you or you have stories you would like to share, please either comment below or email him directly.

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John Choi

John Choi is a lactose intolerant medical student who believes in the power of sharing stories and, regretfully, loves cheese.

Basic biology tells us that in humans and other mammals, embryos with two X chromosomes develop as females, whereas embryos with one X and one Y chromosome develop as males. If only it were that simple. As it turns out, genetic makeup doesn’t fully determine which sexual organs will develop in utero.

iStock-613773660Every developing embryo, irrespective of its sex, at one point contains both male and female reproductive tracts, referred to as the wolffian duct and the müllerian duct, respectively. If the fetus produces testosterone and the anti-müllerian hormone (AMH) gene products from the Y chromosome — these molecules elicit cellular signaling events that lead to the destruction of the female müllerian ducts. The wolffian ducts subsequently develop into male reproductive organs, such as the seminal vesicles, vas deferens and accessory structures. In the absence of testosterone or AMH, the wolffian ducts degenerate and the müllerian ducts develop into female reproductive organs including the fallopian tubes, uterus, cervix and upper vagina. These pathways were first identified and elucidated in the 1940s by the French endocrinologist Alfred Jost, who conducted intricate experiments using rabbits and showed that female development is a "default" pathway that needs to be actively overridden for the development of male sex organs.

A new study published in Science by Humphrey Yao, Ph.D. challenges this age-old concept of the female pathway as “default” and shows that the development of femaleness is also an active process. The authors implicated a protein called COUP-TFII as a key player that is required to actively eliminate the wolffian duct in a developing female embryo in order to give it female characteristics.

Before we are born, a set of embryonic structures form the basis of our male or female reproductive organs. These embryonic structures are known as Wolffian and Müllerian ducts The researchers had originally set out to study how tissues on the outside of the early ducts communicate with the lining of the tubes in the early embryo to direct proper organ development. Since the COUP-TFII protein is produced in that outer layer, Yao suspected it could play an important role in this signaling process. His team mutated the gene for COUP-TFII in mice so that this protein was no longer produced by the developing embryos. They observed that in these mutant mice the communication in the reproductive tissue of early female mouse embryos was disrupted. However, what was surprising was that these female embryos retained not only the female müllerian duct but also the male wolffian duct.

The researchers investigated whether the female embryos made extra testosterone that could explain the retention of the wolffian duct; however, the testosterone levels in the mutant female embryos were unchanged. Instead, the team found that COUP-TFII activated signaling pathways that actively destroy the wolffian duct in females. In the absence of this protein, the male ducts are not destroyed, a process that was previously thought to proceed in XX embryos by default. Another surprising observation was that genetically XY male embryos mutant for the COUP-TFII gene had intact wolffian ducts even though they didn’t produce testosterone. This showed that, unlike what was earlier believed, male embryos are capable of developing male tubes in the absence of signals from testosterone and AMH, and that the development of female sex organs does not proceed by “default” but rather requires the coordinated action of specific signaling proteins.

Although the study was conducted in mice, COUP-TFII is also produced by human embryos, making it highly likely that the pathway identified here may work the same way in humans. This study widens our understanding of the processes that govern the proper development of sex organs and has the potential to help understand disorders of sex development in humans.

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Monika Deshpande

Monika Deshpande is passionate about science communication. When she was a postdoc at the National Institutes of Health, she was involved in several publications, such as The NIH Catalyst and NIH Research Matters. She is adept at interviewing scientists and showcasing their achievements, and is able to write for scientific and nonscientific audience.

When scientists and clinicians hear the words “clinical trial”, we may think of hope, discovery, and a new chance at life. But for racial and ethnic minorities, these words may not have the same positive connotation but may rather be associated with inaccessibility, fear, and exclusion. The potential benefits for patients who participate in clinical trials are numerous, including free or reduced drug costs, access to new treatments that are otherwise not available, and an overall better standard of care. However, many patients from minority populations do not have access to these benefits, as was recently highlighted in a multi-institutional study led at Johns Hopkins by Jennifer Wenzel, Ph.D., studying increased minority involvement in clinical trials by bolstering clinical and research professional training.

Facing Barriers to Enrollment

Overall, enrollment in clinical trials is minuscule, with less than 5 percent of all cancer patients currently enrolled in a clinical trial. While this small number is an issue in and of itself, a further problem is that of enrolled patients, less than 10 percent are racial and ethnic minorities, and African Americans are only 60 percent as likely as whites to enroll in clinical trials. These numbers are especially concerning given that cancer mortality is higher in the majority of tumor types and stages for African American patients than for non-Hispanic whites, and African Americans are more likely to have advanced disease at diagnosis.

While the National Institutes of Health (NIH) Revitalization Act in 1993 requires that medical research paid for by the NIH include women and minorities, it does not provide adequate instruction on minority enrollment. Furthermore, as only approximately 6 percent of United States, clinical trials are funded by the NIH, the majority of trials do not abide by this requirement.

The issue of minority enrollment and retention in clinical trials is multifaceted, with the mindset of both patients and clinicians/scientists playing a role. Minority patients may have less access to clinical trials, as minorities are more likely to rely on under-resourced hospitals for care. As most clinical trials are conducted in large urban areas, fewer individuals from rural areas are included.

Additional financial barriers also exist, including transportation and/or lodging costs, and limited sick leave. There is also a level of general mistrust towards research professionals and clinical trials after several historical cases in which minority research subjects’ rights were violated, including the Tuskegee study. Lastly, minority populations have a higher likelihood of being diagnosed with other chronic diseases (including obesity, diabetes, or asthma) that traditionally have excluded them from participating in clinical trials.

Besides these socioeconomic and geographical factors, Dr. Wenzel calls on research professionals and clinicians to play a role in enrollment disparities as well. Finding minority patients often takes longer and requires more effort. Without the mandate to do so, many researchers choose not to spend extra time and resources on recruiting minority populations. Dr. Wenzel’s findings show that research staff, principal investigators, and primary care physicians hesitate to include minority patients in their research because they view it as a burden on individuals who may be overwhelmed by other aspects of their lives.

Did you know that less than 10% of cancer patients enrolled in a clinical trail are racial or ethnic minoritiesSolutions Focus on Recruitment, Retention and Return

There is much that can be done to address this complex issue. As the Eliminating Disparities in Clinical Trials (EDICT) report by the Intercultural Cancer Council stated, researchers must focus on the “three Rs” — recruitment, retention, and return. Researchers must not only actively recruit minority populations, but must also work to retain patients by overcoming any transportation barriers, insurance issues, and/or language barriers. The American Society of Clinical Oncology (ASCO) has encouraged researchers and clinicians to expand eligibility criteria such that more patients are eligible for trials, potentially allowing more minorities with existing comorbidities to participate.

At Johns Hopkins, a NIH-supported partnership between the Johns Hopkins Kimmel Cancer Center and the Howard University Cancer Center started in 2001, was established to focus on research, outreach, education, and training on cancer health disparities associated with minority populations and cancer treatment. Hopkins is also working to address these disparities through Dr. Wenzel’s work with the multi-institutional EMPACT (“Enhancing Minority Participation in Clinical Trials”) program which specifically focuses on the problem of minority recruitment training for research professionals.

Through this study, Dr. Wenzel has learned that many researchers are not adequately trained but notes that better training can bridge gaps between professionals and patients, providing many benefits. She states that a great support system comes from “patient navigators”, who work with patients to provide information on available clinical trials, resources to solve logistical barriers, and emotional support and recognition of specific minority needs.

Moving forward as an institution, as well as the next generation of clinicians and scientists, we must acknowledge the large disparity that exists in clinical trial enrollment with minority populations. We must take steps to enroll more minority patients in clinical trials, so that they may reap the benefits of having access to life-saving therapeutics, while in turn benefiting the studies by giving more generalizability of the study for more patients.

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Brittany Avin

Brittany Avin is a Ph.D. candidate in molecular biology and genetics. She is a cancer survivor, cancer researcher, and cancer advocate who’s passionate about closing the communication gap between patients, clinicians and researchers.

I have people contacting me from all over the country. A pastor called me after an interview I had with CBS  and told me, "you still look, talk, and smell like a convict." Wow. What does a “convict” smell like? He continued, "You need Jesus in your life. Back in my day, people were ashamed to have gone to prison. You seem proud. That's what's wrong with you young black folks." He even threw in a 5-minute rant to let me know that I was going to hell.

I tried to not let his words dig too deep. I have been told by many on this journey to let the negative comments and hate fall to the side. I agree. I would not have made it from prison cells to PhD and a scientist at Johns Hopkins if I had let all the people who told me, “You can’t,” get the best of me. But, the pastor brought up some points I’d like to unpack

avoid using the words convict and inmate. Rather, refer to them as incarcerated individuals and people.

click to enlarge

First, I’m not proud to have gone to prison. I would not wish what I went through on my worst of enemies. The trauma I endured. The violence I witnessed. The dehumanizing nature of our criminal justice system inmates suffer.

I am deeply torn, broken, hurt, scarred, and changed by my prison experience. But, also, I grew, improved, learned, endured, battled, fought, strived, and changed for the better through my prison experience. The painful humiliation rang deep in my bones every night from full to new moons. I fell so deep in my shame that my thoughts would take me to places that no one wants to be. I don't want to live in my painful humiliation any more. The psychological damage of prison is one of many collateral consequences that are perpetuated by the words and negative views society shares towards people with criminal convictions.

Most importantly, I am a person with a criminal conviction who spent time in prison. I am not a convict. I am not a felon. These are words used by society and the criminal justice system as a reminder that I am viewed as less than a person, that I am viewed as less than you.

I am a person. These words are dehumanizing, demoralizing, and derogatory, yet they are embedded in the way we talk about people with criminal convictions. We cannot move forward until we leave behind these damaging and stigmatizing words.

To the same respect, clinicians are taught to never refer to a patient as their disease. It is dehumanizing, damaging and stigmatizing. For example, we are taught not say “that cancer patient” and instead to say “the person, who is suffering from cancer”. It reminds us that as humans, we are more similar than we are different. Throughout history, “othering” has repeatedly lead us down a damaging path. As individuals, and as doctors, we can make a difference.

About this series

From Prison Cells to PhD is a series following the journey of Dr. Stanley Andrisse, who was convicted of two felony drug charges and sentenced to 10 years in Missouri prison, and is now a postdoctoral scientist in pediatric endocrinology and trainee leader at Johns Hopkins Medicine.


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Stan Andrisse

Dr. Stanley Andrisse was convicted of two felony drug charges and sentenced to 10 years in Missouri prison. He is now a postdoctoral scientist in pediatric endocrinology and trainee leader at Johns Hopkins Medicine.

“...23,000 deaths a year.”  “...over 2 million infections.”  These headlines would be alarming but expected if they were descriptions of the latest Ebola outbreak. But alas, these are “conservative, minimum estimates” of antibiotic-resistant infections each year in the United States, as projected by the Centers for Disease Control and Prevention.

The Dangers of Antibiotic Resistance

According to CDC data from 2013, antibiotic resistance results in more than 2 million illnesses and 23,000 deaths every yearAntibiotics are the lynchpin of modern medicine. Without their targeted efficacy against bacteria, minor surgeries are life-threatening endeavors; diseases we largely consider conquered, such as pneumonia and tuberculosis, become fatal again; and childbirth is a massive risk to mother and child alike. For many years, our arsenal of different classes of antibiotics has drastically improved the life- and health spans of humans across the world, by giving physicians an on-demand way to swiftly inhibit the growth of some of the most ubiquitous, and disease-causing microorganisms.

However, all life under selective pressure evolves and, over generations, bacterial strains have built a repertoire to evade, escape and denature these compounds. Of course, because of our society’s heavy reliance on antibiotics, the genes that confer resistance spread rapidly within the bacterial world and ultimately emerge as a new antibiotic-resistant pathogen. The most common examples are now household names, such as MRSA, or methicillin-resistant Staphylococcus aureus, the notorious scourge of hospitals and athletic facilities alike, or the recently emerged superbug CRE (carbapenem-resistant Enterobacteriaceae), among others. The root causes for this spread are multifold: overprescription of antibiotics, premature termination of antibiotic treatment by patients, and incomplete infection-control standards in high-risk areas like hospitals.

Optimizing the Use of Antibiotics

The problem of antibiotic resistance is clear to all in the medical field. The need for new classes of drugs is immense and pressing, but resistant strains are emerging rapidly, while development of new antibiotics has slowed dramatically. One strategy being utilized at Johns Hopkins to address these issues is the Antimicrobial Stewardship Program (ASP), a consortium of physicians and researchers tasked with developing guidelines to optimize the use of antibiotics in a hospital setting and ensuring patients receive the drugs they require, as a means to prevent the development and spread of resistant strains.

The ASP has been publishing comprehensive guidelines for antibiotic administration since 2001. As a team, the group synthesizes information from myriad doctors and researchers, both local and nationwide, to offer standardized suggestions for each antimicrobial agent as well as each use case. These guides are available to all physicians, who should then be able to optimize the drugs prescribed to each patient, while simultaneously combating the spread of antibiotic resistance writ large.

According to the ASP at Johns Hopkins, 30 percent of all antibiotics utilized in a hospital setting are incorrect or unnecessary. The litany of misuse includes overprescription and suboptimal antibiotic choice for individual cases. It is these types of situations the ASP hopes to rectify, and their guidelines are constantly being refreshed and revised using new information acquired from doctors’ experiences, as well as ongoing research on various outcome measures and improving delivery systems.

Unfortunately, even if the ASP is entirely successful and able to optimize antibiotic deployment to 100 percent efficiency, the rise of resistant strains will likely continue to seriously affect health care in both the immediate and long term. Until a new technology allows us to directly counteract infections, humans will always require drugs capable of specifically beating back the growth of disease-causing microbes. Although discovery of new classes of antibiotics has slowed considerably, a number of researchers have begun to search widely for new substances with antimicrobial properties. Like their predecessor, Alexander Fleming, these researchers are sampling diverse bacteria, fungi and other types of microbes throughout the world looking for endogenous, already-evolved bacterial defense mechanisms that can be tweaked or altered to build the next class of potent antibiotics for human use.

This will be an eternal battle. New antibiotics will be developed and used to further human health, while the organisms they are designed to kill will develop ways to evade them, and the predator-prey relationship continues. It is vital that the progress of new antibiotic research outpaces the emergence of resistant ‘superbugs,’ and this perpetual evolutionary race is why the ASP is so important now as well as far into the future.

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Benjamin Bell

Benjamin Bell studies sleep and circadian rhythms in mice and flies, and is fortunate the mice understand his semi-nocturnal work schedule. When not actively in the lab, you can find him thinking about research and science-writing on his motorcycle, on the hiking trails, or at any local concert venue.

For the first time ever, scientists in the United States have performed gene editing experiments using CRISPR-Cas9 in humans. CRISPR-Cas9 is a bacterial DNA editing system that researchers have harnessed to change the specific sequence of DNA, with precision down to a single letter of the DNA code. Many pilot studies have been done in the five years since CRISPR’s initial discovery as a genetic engineering tool; most have worked to prove its efficacy, safety and ease of use. Now that scientists have established the potential of this tool, the question arises: Can we use this to manipulate the human genome?

Manipulation of DNA with bare hands, tweezers and a scalpel - drawing

In a Nature report, Shoukhrat Mitalipov and colleagues at the Oregon Health and Science University reported their success in correcting a mutation that is known to cause hypertrophic cardiomyopathy, a heart disease that affects about one in 500 adults, and the most common cause of sudden death in healthy athletes. Because the condition doesn’t manifest until later in life, adults often pass on the gene unknowingly;  50 percent of children from an affected parent will inherit the disease.

The heart condition can be caused by variants, or changes to the DNA sequence, of any of nine genes, including one called MYBPC3. Although advances in in vitro fertilization now allow parents to choose embryos that do not harbor these changes, the success of this method is limited by the 50 percent inheritance rate. In such cases, gene editing could potentially allow for embryos harboring deleterious variants to be corrected and implanted, leading to more healthy pregnancies and, correspondingly, more healthy adults without hypertrophic cardiomyopathy.

. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats and it is a genome editing technology that allows scientists to permanently modify genes in living organisms or cells.

Using CRISPR-Cas9 gene editing, Mitalipov et al. were able to correct the disease-causing MYBPC3 variant in 67 percent of human embryos. Due to off-target effects, some of the editing events lead to errors, completely destroying gene function in the edited copy, while other embryos were not edited at all. Even so, the high efficiency and accuracy of editing demonstrated by the authors are promising results. However, none of the embryos in this study were implanted or allowed to progress to pregnancy. This report established the safety and efficacy of using CRISPR-Cas9 to edit human embryos, beyond the work already done in cell lines or animal models, but it does not answer many underlying questions about changing the blueprints of human cells.

One day after the Nature report, the American Society of Human Genetics, along with many collaborators, published a statement to guide further genetic editing experiments in humans. At this time, they caution that many scientific and ethical questions remain regarding altering human genome. Therefore, they argue, no gene editing that can be passed on to the next generation should be allowed to progress to pregnancy. However, the group of scientists does not believe that all work on human embryos should stop, and suggests that more experiments using donor embryos and gametes could help to facilitate research regarding future clinical applications.

Lastly, they urge that any use of gene editing as a clinical treatment should only occur if it meets the four following criteria: a compelling medical rationale, an evidence base that supports its clinical use, an ethical justification, and a transparent public process to solicit and incorporate stakeholder input. Right now, human genome editing is in its infancy. More work is needed to ensure that efforts meant to correct gene function only benefit patients, as well as to ensure that other treatment options aren’t more feasible or cost-effective. Policy makers need input from physicians, patients and the public to ensure that small changes don’t cause big, undesirable consequences for society.

The story of CRISPR and gene editing, in humans and the U.S., is only just beginning. With these tools, scientists and physicians have great power and great responsibility, the promise of healing many genetic diseases just on the horizon.

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About the Author

Sarah Robbins

Sarah Robbins is a human genetics Ph.D. student. Her skill at reading recipes has made her able to translate her talents from pies to PCR.