Typewriter alongside human feet and cat's tail

So You Want to Be a… Freelance Medical Writer

By Elizabeth Ohneck, PhD

In the first post of our So You Want to Be a… series we talked to Elizabeth Ohneck about her career as a medical writer. This week Elizabeth interviewed Ginny Vachon who runs her own medical writing company, Principal Medvantage, to find out what it takes to go it alone and become a freelance medical writer.

 

What does a freelance medical/science writer do?

Medical writers can do many different types of writing, but in general, medical writing is centered on taking information and making it accessible and informative for the correct audience. For example, taking raw data and writing a manuscript for other physicians is really different than summarizing recent findings for the general public. Freelance medical writers are contractors, and can be called in by pharmaceutical companies, communications agencies, medical associations, or other groups to help with specific projects that can’t be handled ‘in house,’ for whatever reason. There’s a ton of variety and opportunity to learn about different diseases. Some freelancers specialize, and write mostly about certain medical areas, or for certain audiences.

 

How did you get where you are now?

I have a BA in Biology from Agnes Scott College and my PhD is from Emory University. As I was nearing the end of my PhD I realized I had no clue what I wanted to do next. I totally froze because I knew I had choices, but I didn’t know how to make the next step. I realized that before I could pick a direction, I needed to learn about all of the different things I could do and how the people who were doing those things spent their days. So, I joined Women in Bio Atlanta and started going to events held by Emory and by WIB. I went to a WIB event on women in business and I heard Emma Nichols, who owns Nascent Medical Communications (formerly Hitt Medical Writing), talk about her experiences as a freelance medical writer and entrepreneur. I spoke with her after the event, and ended up doing a number of projects for her. After getting some experience, I started my own company! She has a great podcast, medical writers speak, that is full of great information about both medical writing and the business side of freelancing. The American Medical Writer’s Association also has a great website, training course, and chapter meetings where you can meet other medical writers and take short courses.

 

What are the key skills needed to be successful at this job, and did you develop any of them during grad school?

I think that the most important thing is a willingness to tackle any subject and learn about it. I think that as a Ph.D. student, I learned that discomfort and anxiety are totally normal when learning something new, and usually happen right before you understand something! I also had my daughter during my third year of graduate school, and developing the level of organization that I needed to ‘do it all’ has been awesome.
Medical writing is really great in that you can get a little bit of experience as a contractor before you graduate. Even if you end up not being wild about medical writing, you have a new skill to set you apart. Who on earth doesn’t want to hire someone who is skilled in communicating complex ideas?

 

What would be your advice to a PhD wanting a similar job as yours?

I would say to listen to the Medical Writers Speak podcast, go to the AMWA website, and start developing samples, writing for a blog or university paper are great starts (the manuscript you wrote with your PI isn’t the best sample) I think a lot of people who are trying to break into medical writing have a hard time with the transition from being a scientist or physician who can write to being a writer who understands science. I think that it’s important to recognize that while obtaining an MD or PhD is really hard, it is only a piece of the puzzle. The thought of sharpening your writing skills should be an exciting one! I know I heard this said at a lot of ‘alternate career events,’ but what you do next should not be a ‘back-up plan,’ it should be an exciting new set of goals! Also, after doing a ton of lab work, I really had a hard time sitting all day. Now I have to be a lot more deliberate about exercise and working with my hands in other ways.

 

What are the top three things on your To Do list right now?

A typical day usually starts with assessing deadlines. I usually have a few projects going on at once, so organization is really important. Today I have to check in with a client who owes me a transcript of an interview, look over a manuscript I finished two days ago with ‘fresh eyes’ before sending it off, and do some bookkeeping (scanning receipts from a recent work trip out of town).

 

What are your favorite parts of the job? What are your least favorite or most challenging parts?

My favorite part is that I get to solve problems for clients. Usually I get called in when people are stretched thin. It’s nice to be able to help companies when they are growing. My least favorite thing is the sitting. I have a standing desk now, which helps, but I miss the constant motion of lab work.

 

Is there anything you miss about academia? What was the biggest adjustment in moving from the bench to your current position?

Yes, of course! I miss being an ‘expert’ in a scientific area. As a writer, I learn just enough about a subject to write well about it. I have totally lost money on jobs before because I get sucked into a topic and next thing I know I am well-versed in how a specific trial recorded adverse events, but it doesn’t matter because that wasn’t what I was supposed to be doing. Especially as a freelancer, it’s all about doing what needs to be done to complete a project. I miss the freedom of diving into a single sentence in a paper to figure out the nature of a problem. The hardest part about making the mental switch was understanding that my role is to produce clear and meaningful content, not to assist in guiding the direction of research or marketing, or whatever the problem is I am writing about. Again, the switch from being a scientist to a writer.

 

How do you see your field developing over the next ten years?

I think that the ways in which medical writers develop content over the next few years will change to include more interactive platforms. I expect that soon doctors and patients will be unsatisfied with brochures, which will not only seem old-fashioned, but be insufficient for the increasingly complex decision-making that accompanies personalized medicine. Probably medical writing will soon include more content for apps. I don’t know that the clinicians of tomorrow will put up with PowerPoint-based CME, or posters will remain paper-based and non-interactive. It is hard to predict how communication will change in ten years time, but I think the most flexible and willing to learn medical writers will be the most successful.

 

What kind of positions to people in your position move on to?

One of the coolest things about freelance medical writing is that it can serve as a grand tour of many different types of biomedical businesses. You get to work with many types of companies (big, small, growing, pharma, CROs, communications firms, medical associations – you name it). You also get to work with the people in a company and see what they are like and see many different styles of working (fast, slow, organized, totally insane – you name it!). You can really observe and learn about what suits you. Many companies who need freelancers also need an on-staff medical writer, or someone smart in medical affairs, or marketing, or communications. Showing up and being organized and pleasant can prompt a job offer.

 

And finally: In the event of a zombie apocalypse, what skills would a freelance medical writer bring to the table?

I could be sure that every conceivable population of clinicians is well aware of how to identify, appropriately treat, and report zombie-related medical events. In addition, all potential patient populations will be well aware of how to seek out specialists, should they experience symptoms. Because I’m a freelancer, I am available to handle any writing needs that crop up as various new anti-zombie therapies emerge.


Genome

How Low Can You Go? Designing a Minimal Genome

By Elizabeth Ohneck, PhD

How many genes are necessary for life? We humans have 19,000 – 20,000 genes, while the water flea Daphnia pulex has over 30,000 and the microbe Mycoplasma genitalium has only 525. But how many of these genes are absolutely required for life? Is there a minimum number of genes needed for a cell to survive independently? What are the functions of these essential genes? Researchers from the J. Craig Venter Institute and Synthetic Genomics, Inc., set out to explore these questions by designing the smallest cellular genome that can maintain an independently replicating cell. Their findings were published in the March 25th version of Science.

The researchers started with a modified version of the Mycoplasma mycoides genome, which contains over 900 genes. Mycoplasmas are simplest cells capable of autonomous growth, and their small genome size provides a good starting point for building minimal cells. To identify genes unnecessary for cell growth, the team used Tn5 transposon mutagenesis, in which a piece of mobile DNA is introduced to the cells and randomly “jumps” into the bacterial chromosome, thereby disrupting gene function. If many cells were found to have the transposon inserted into the same gene at any position in the gene sequence, and these cells were able to grow normally, the gene was considered non-essential, since its function was not required for growth; such genes were candidates for deletion in a minimal genome. In some genes, the transposon was only found to insert at the ends of the genes, and cells with these insertions grew slowly; such genes were considered quasi-essential, since they were needed for robust growth but were not necessary for cell survival. Genes which were never found to contain the transposon in any cells were considered essential, since cells that had transposon insertions in these genes did not survive; these essential genes were required in the minimal genome.

The researchers then constructed genomes with various combinations of non-essential and quasi-essential gene deletions using in vitro DNA synthesis and yeast cells. The synthetic chromosomes were transplanted into Mycoplasma capricolum, replacing its normal chromosome with the minimized genome. If the M. capricolum survived and grew in culture, the genome was considered viable. Some viable genomes, however, caused the cells to grow too slowly to be practical for further experiments. The team therefore had to find a compromise between small genome size and workable growth rate.

The final bacterial strain containing the optimized minimal genome, JCVI-syn3.0, had 473 genes, a genome smaller than any autonomously replicating cell found in nature. Its doubling time was 3 hours, which, while slower than the 1 hour doubling time of the M. mycoides parent strain, was not prohibitive of further experiments.

What genes were indispensable for an independently replicating cell? The 473 genes in the minimal genome could be categorized into 5 functional groups: cytosolic metabolism (17%), cell membrane structure and function (18%), preservation of genomic information (7%), expression of genomic information (41%), and unassigned or unknown function (17%). Because the cells were grown in rich medium, with almost all necessary nutrients provided, many metabolic genes were dispensable, aside from those necessary to effectively use the provided nutrients (cytosolic metabolism) or transport nutrients into the cell (cell membrane function). In contrast, a large proportion of genes involved in reading, expressing, replicating, and repairing DNA were maintained (after all, the presence of genes is of little use if there is no way to accurately read and maintain them). As the cell membrane is critical for a defined, intact cell, it’s unsurprising that the minimal genome also required many genes for cell membrane structure.

Of the 79 genes that could not be assigned to a functional category, 19 were essential and 36 were quasi-essential (necessary for rapid growth). Thirteen of the essential genes had completely unknown functions. Some were similar to genes of unknown function in other bacteria or even eukaryotes, suggesting these genes may encode proteins of novel but universal function. Those essential genes that were not similar to genes in any other organisms might encode novel, unique proteins or unusual sequences of genes with known function. Studying and identifying these genes could provide important insight into the core molecular functions of life.

One of the major advancements resulting from this study was the optimization of a semi-automated method for rapidly generating large, error-free DNA constructs. The technique used to generate the genome of JCVI-syn3.0 allows any small genome to be designed and built in yeast and then tested for viability under standard laboratory conditions in a process that takes about 3 weeks. This technique could be used in research to study the function of single genes or gene sets in a well-defined background. Additionally, genomes could be built to include pathways for the production of drugs or chemicals, or to enable cells to carry out industrially or environmentally important processes. The small, well-defined genome of a minimal cell that can be easily grown in laboratory culture would allow accurate modeling of the consequences of adding genes to the genome and lead to greater efficiency in the development of bacteria useful for research and industry.


A typewriter drawn on a turquoise background

So You Want to Be a… Medical Writer

By Sally Burn, PhD

What can you be with a PhD? So many things! In our new series on post-PhD careers we explore the options out there, providing tips on how to break into different industries and helping you identify jobs your skill set is ideally matched to. Check back every two weeks for the lowdown on becoming, to name but a few, a Publisher, Tech Startup Founder, Medical Science Liaison, Editor, Industry Scientist, Consultant, and Space Pirate (OK, so perhaps not the last one).

Today, in our first post, we chat with Elizabeth Ohneck about her career as a Medical Writer and find out how you can become one too. Elizabeth works for Health Interactions, a medical education and communications agency; she’s also one of our regular Scizzle blog contributors.

 

Hi Elizabeth! So, what exactly does a Medical Writer do?

Medical writers work with research teams in pharmaceutical, nonprofit, and other institutions to develop manuscripts, abstracts, posters, and presentations. In general, our clients send us reports outlining the methods, results, and analysis parameters of their studies, which we use to develop the desired publications or presentations. We also attend conferences and prepare conference summary reports, as well as write literature reviews over current publications in a particular disease or therapeutic area. In addition, we provide support for administrative tasks such as manuscript and abstract submission and the preparation of biosketches for physicians and researchers.

 

How did you get to where you are now?

I have a BS in Biology from the University of Dayton, where I first experienced working in a lab for my honors thesis in microbiology. I enjoyed research at the time, so I decided to go to grad school. I got my PhD from Emory University in Microbiology and Molecular Genetics. I knew I didn’t want to stay in academia, but wasn’t sure what I wanted to do, so I took a postdoc position at NYU while I looked into other career options. I’ve always liked writing and am often frustrated by how poor the communication of science is among researchers and between researchers and the public, so I started looking for opportunities in science communication. My husband is a postdoc at Princeton, and a former postdoc from his department emailed the department saying his company was hiring medical writers and any interested candidates should contact him. My husband sent me his information and I emailed him to set up an informational interview. After our conversation, he sent my CV to the HR department at his company and from there I went through the standard hiring process – phone interview, writing test, in person interview, job offer.

 

What are the key skills needed for this job? Did you develop any of them during your PhD/postdoc?

You really have to love learning and be an effective self-educator. I work in rheumatology and veterinary medicine right now, not areas at all related to my background in microbiology. So I had to learn a lot about new subjects very quickly, and it’s really important to stay up-to-date with the research and developments in the field. And you obviously need to enjoy writing and have strong communication skills. Time management and the ability to meet deadlines and prioritize work are also critical. A PhD and postdoc should help you develop all of these skills through planning your research, preparing publications and presenting your work. The ability to professionally and effectively communicate with clients has probably been the skill I needed to work on the most, since it requires much more formal communication than we usually use in academia.

 

What would be your advice to a PhD wanting a job similar to yours?

Take every opportunity you can to write and present. In addition to your own manuscripts, take advantage of any offers to contribute to book chapters, reviews, commentaries, etc. Write for a research blog (like Scizzle!) or a department or program newsletter. Attend conferences or participate in symposiums or presentation opportunities at your institution to become comfortable and efficient with poster and oral presentations. For entry-level medical writing positions, effective scientific communication skills will really be the key to demonstrate that you are a strongly qualified candidate. And network. I know everyone says that for every position, but it’s true. Create a professional social media presence and look for opportunities to meet people in the field.

 

What are the top three things on your To Do list right now?

Right now, I need to finish editing the monthly rheumatology literature review we prepare for our rheumatology clients, submit a manuscript, and prepare an outline for a new manuscript that we will be kicking off next week.

 

What are your favorite – and least favorite – parts of the job?

My favorite part of the job is writing manuscripts. It’s the most writing-intensive task, and writing is really my passion. I love the feeling of accomplishment that comes with turning a collection of data into an intelligible story. My least favorite part is making slide presentations, but that’s only because I’ve never been particularly fond of the software used to make said presentations. The most challenging part for me is conference coverage. Travel to and from the conference, long days of taking detailed notes during conference sessions and meeting with clients, and tight deadlines for creating conference summary documents afterward can be exhausting. But getting to travel to new places is fun.

 

Is there anything you miss about academia? What was the biggest adjustment or most challenging aspect of moving from academia to your current job?

I don’t miss anything about being at the bench or the academic environment. The experience helped get me where I am today, but it just wasn’t the right fit for me long term. The biggest adjustment was getting used to not being on my feet all day – I have to remember to get up to walk around and stretch every once in awhile! The biggest challenges were learning the writing style preferred by our clients and adapting to the more formal style of communication required for interaction with clients.

 

How do you see your field developing over the next ten years?

From what I understand, there is a huge demand for people in the medical communications industry, so it seems that it’s a growing field. I imagine this growth will continue, since there is increasing demand for more transparency in scientific research, and medical communications companies can help increase the clarity of publications and the efficiency of the publication process.

 

What kind of positions does someone in your position move on to?

The next step after entry-level Medical Writer is Senior Medical Writer, which involves more projects, more independence and leadership in your projects, and opportunities to mentor newer medical writers. In my company, the next step would then be Associate Scientific Director, which involves more management responsibilities.

 

Finally, the all-important question: In the event of a zombie apocalypse, what skills would a Medical Writer bring to the table?

I imagine we’d be responsible for informing the public about the virus or genetic mutation (it’s always one of those) that’s causing the zombie condition and communicating information about the cure. Although, as far as how we would distribute that information – that might be outside of our job description. If you figure out what career that would be, let me know. It’s never too early to start networking…


plastic duck

A Newly Discovered Bacterium Finds Plastic Fantastic

 

By Elizabeth Ohneck, PhD

We produce over 300 million tons of plastic each year. One of the most abundant forms of plastic is polyethylene terephthalate, or PET, a polyester frequently used in fabrics and the primary component of plastic beverage bottles and other types of food packaging. In 2013, approximately 56 million tons of PET were produced worldwide, but only about 2.2 million tons were recycled. The high demand for PET drives increased production of its monomers, terephthalic acid and ethylene glycol, both of which are industrially derived from petroleum, leading to high consumption of oil. The ubiquitous presence of PET and its resistance to biodegradation – it takes 5 to 10 years to naturally degrade – has led to a massive accumulation of PET in the environment, leaving us searching for ways to clean up the mess.

Nature may have just offered us a helping hand. Researchers from Japan have identified a bacterial species, which they’ve named Ideonella sakaiensis 201-F6, capable of breaking down PET to use as a food source. Their findings were published this month in Science.

The research team collected 250 environmental samples from soil, wastewater, sediment and sludge outside a PET bottle recycling plant and cultured the samples with PET films. One sample contained a bacterium that, when isolated, was able to grow with PET as the sole carbon source and to completely degrade the PET film in 6 weeks at 30°C (86°F). Genome sequencing of Ideonella sakaiensis 201-F6 identified two enzymes, subsequently called PETase and MHETase, with weak homology to enzymes from fungi previously shown to have PET-degradation activity. Purified PETase and MHETase were able to break down PET films to produce terephthalic acid and ethylene glycol. Interestingly, PET has only been produced since the 1940s, meaning the evolutionary window for such a drastic metabolic adaptation is relatively short, particularly since PETase and MHETase bear little resemblance to even the most closely related enzymes known in other species. When and how PETase and MHETase arose thus remain a mystery.

These findings have several important implications. Ideonella sakaiensis 201-F6 is not only able to degrade PET, but can subsequently metabolize the resulting terephthalic acid and ethylene glycol, which, while far more environmentally friendly than PET, are toxic at high levels. By using terephthalic acid and ethylene glycol as a food source, Ideonella sakaiensis 201-F6 is able to remove PET and its breakdown products from the environment. An exciting application would be isolation of the terephthalic acid and ethylene glycol to use in the production of new plastic. Recovering and reusing the PET monomers would drastically reduce the amount of oil needed to produce plastic, and allow true recycling of PET into fresh plastic suitable for packaging, rather than the current recycling tactic of melting and reforming PET plastic into other products.

Obviously, more research remains to be done before Ideonella sakaiensis 201-F6 or its PET-degrading enzymes are useful on a large scale. Reducing the time of PET degradation from decades to weeks could be beneficial in contaminated ecosystems, but adaptations to further speed the process are necessary for practical use at the industrial level. Additionally, the ability of Ideonella sakaiensis 201-F6 to survive in varying habitats and disruptions it might cause to specific ecosystems need to be carefully considered before releasing this bacterium or an adapted version into other environments for PET cleanup.

Nevertheless, the discovery of a bacterium that can degrade PET is promising for our efforts to combat the havoc our plastic-dependent lifestyle is creating in the environment. The PET-metabolizing power of Ideonella sakaiensis 201-F6 is a testament to the adaptability and resiliency of nature. Hopefully this discovery sparks new ideas and research into healthier and more efficient means of plastic production and recycling.


A questioning robot

The Non-academic Job Hunt: Questions TO Interviewers

 

By Elizabeth Ohneck

Congratulations! You’ve made it to the end of your non-academic job interview! Well, except for that inevitable last question: “Do you have any questions for us?” After an intense period of answering tough questions from the interviewer, it’s your turn to drive the conversation, and for some of us, it’s the scariest part. It’s very important to ask questions, to show you are as interested in learning about the position and the company as they are in learning about you. Not asking questions cuts the conversation short and can be viewed negatively by the interviewer. But your first interview isn’t the time to ask about salary, benefits, dress code, etc. – these questions will be answered when an actual offer is discussed. Instead, you want to ask questions that continue to demonstrate your qualifications for, interest in, and commitment to the position, while providing you with crucial information about the job. So what kind of questions should you ask? Here are a few examples of general questions to get you started:

 

  • What do you enjoy most about working with this company? Initiating this conversation will connect you to the interviewer on a more personal level. The answer can also give you insight into company values, as well as an idea about how satisfied employees are with their jobs – if the interviewer struggles to come up with an answer, it could be a red flag about the working conditions.

 

  • Can you tell me about the team I will be working with? By asking this question, you are demonstrating your readiness to be a team player. The answer will tell you about the people you will work with on a daily basis and give you an idea about how individuals contribute to accomplishing team goals.

 

  • What constitutes success in this position and at this company? This question shows your desire to be successful in the job, and the answer can provide useful information about whether the position is a good fit for you, as well as how to succeed and get ahead in the company.

 

  • What skills and experiences would make an ideal candidate? The answer to this question will reveal exactly what the employer is looking for, and can give you the chance to affirm how your background meets those criteria or to discuss how you plan to gain or develop the desired skills.

 

  • What is one of the most important challenges currently facing your team, and would I be in a position to help resolve this problem? This question shows you are already thinking about how you can help the company. It also encourages the employer to envision you actually working in the position.

 

  • Do you offer continuing education or professional training? This question shows your interest in expanding your knowledge, developing skills beneficial to the job, and growing with the company. The answer may give you an idea as to how new employees are trained, and the value the company places on supporting the professional development of its employees.

 

  • What is the next step in this process? This is an essential last question. It shows you are interested in moving the process along. You may also gain insight into how many other candidates are being interviewed, and will get an idea about the timeline, giving you a chance to prepare for the next step.

 

If possible, it’s a good idea to talk to contacts that have interviewed for or currently hold similar positions to identify questions you can ask that are specific to the job for which you are interviewing. Also, be sure to thoroughly research the company, as it may stimulate relevant questions. Type out a list of your questions and have it easily accessible when the time comes. Having a physical document shows you have put thought and effort into preparing for your interview. It’s also beneficial to practice asking your questions out loud, to ensure you can readily and clearly ask them.

 

Don’t be afraid of the unavoidable last question! With a little preparation, you can confidently guide the end of the interview to provide useful information about the position, the people, and the company, while simultaneously shining a last bit of light on your stellar qualifications.


Answering interview questions badly

The Non-academic Job Hunt: Questions FROM Interviewers

 

By Elizabeth Ohneck

Congratulations! You’ve just been asked to interview for the non-academic job of your dreams! Now it’s time to prepare. But an interview outside of academia can be very different from graduate school, postdoc, and faculty position interviews, and after years spent at the bench, it can be difficult to think of your talents and goals outside of the academic box. For a successful interview, it is crucial to talk about your skills, experiences, qualifications, and goals as applicable to the non-academic environment in which you’ll be working. Preparation of answers to some common questions can help you proceed with confidence through the interview discussion. So what kind of questions can you expect? Here are some frequently asked interview questions, with tips for thinking about your answers:

 

  • Tell us about your scientific/research background. Be able to explain your research in a clear, concise manner at a level appropriate for the audience. Think about your “elevator speech” – if you only had one or two minutes to explain your research, what would you say? Your answer might be very different if you’re in the elevator with another research scientist versus an accountant, an English teacher, a mechanic, or your grandmother (not joking: I was asked how I would explain my postdoc research to my grandma). Someone from the Human Resources department will likely want a different answer than someone working in a position more directly related to science, so make sure you can give answers accessible to multiple audiences.

 

  • Why do you want to leave the bench/academia? For most, the answer to this question is obvious. The challenge is explaining your reasons in a diplomatic manner. “I hate bench research” or “I don’t want to be a PI” may be the simple answers, but what are the deeper reasons for wanting a different career? Perhaps you’re leaving the bench because you feel your strongest scientific talents, like writing or teaching, would be better utilized in a different environment. Maybe you don’t want to be a PI because you want a career that will allow you to spend more time at the bench than many PIs are able. Rather than focus only on what you don’t like about the bench or academia, explain how your strengths and passions are better fit for an alternative career and the position for which you are interviewing.

 

  • Why are you interested in [position]? It’s important to emphasize that you are not applying for this position simply because you can’t get a job in or are desperate to leave academia (even if that is the case). What aspects of this career do you think will be most fulfilling for you? How do your talents and background make this position a good fit for you, and vice versa?

 

  • What are your strengths/what can you bring to this company? The answer to this question may be more difficult for those applying for non-research positions. As graduate students and postdocs, we don’t often think about the skills we are developing other than the technical skills that make us successful at the bench. Reflect on the non-technical aspects of research at which you excel, and relevant experiences away from the bench. Are you a great writer or a stellar presenter? Have you mentored undergraduate and graduate students in the lab that have gone on to be successful in their own research? Did you design a new assay or come up with a novel approach to solve a difficult research question? Think of specific examples of experiences that demonstrate your expertise in qualities essential or beneficial to the position to which you are applying.

 

  • What are you weaknesses? The trick to answering this question is to be honest without being negative. A good suggestion is to frame the negative with a positive on either side. For example, perhaps you have trouble speaking up in large group meetings. You might say something like, “I'm a good listener, which allows me to synthesize the ideas and opinions put forth in a group discussion, but in taking into account everyone else's comments attentively and in detail, I can forget to or have trouble speaking up and providing my own input. In most cases, however, I am able to find an appropriate time to provide my input to help move the project forward.” But again, be honest – we all have weaknesses, and the interviewers want to see that you can critically evaluate your own performance, so “I don’t have any weaknesses” isn’t an appropriate answer.

 

  • How do you handle multiple projects and deadlines? This question should be one of the easiest. As grad students and postdocs, we balance multiple projects all the time. As a grad student, how did you balance classes, studying, and time in the lab? How do you plan for multiple experiments in a day or week to efficiently utilize your time? How do you keep track of multiple research projects? With a bit of reflection, you should be able to come up with some specific examples that show off your time management skills.

 

  • After working as an individual/alone, how will you adapt to working on a team? Many people outside of research have the misconception that scientists work alone, isolated from others at the bench, mired in their own projects. It’s important to (kindly) dissolve this stereotype. Scientists collaborate within their labs, their departments, their institutions, and with outside institutions. We participate in lab meetings, seminars, and conferences to get feedback on our research and provide insight and ideas to others. Discuss with the interviewers your experiences working with other scientists and how these experiences have prepared you for working in a team-oriented environment.

 

  • Where do you see yourself in 5 years/what are your long-term career goals? Your answer to this question should show your enthusiasm for the position and suggest your commitment to growing and developing your career with the company. Why is this position a good next step for you? What skills are you hoping to develop and what experiences are you hoping to gain? You might express interest in taking on management responsibilities or getting involved in certain areas or projects. Show motivation and realistic ambition in this career path.

 

It’s beneficial to talk to other people who have recently applied or currently work in jobs similar to the position you are applying for to get an idea of potential questions specific to the position. Take some time to really reflect on your answers to come up with specific, concise, and sincere answers. Most importantly, practice answering these questions out loud, perhaps with people from a variety of backgrounds - a coworker, a scientist from a different field, someone who works in the career you are pursuing, your grandmother – to ensure you can quickly and efficiently verbalize your thoughts. With preparation and practice, you can ace your non-academic interview and get the job to put you on your way to a fulfilling career.


Teixobactin: Are We Jumping the Gun on a New Magic Bullet?

 

By Elizabeth Ohneck, PhD

The introduction of penicillin to the clinic in the 1940s ushered in an era of hope in our battle against bacterial disease. Penicillin, produced by a lowly mold, Penicillium notatum, was accidentally stumbled upon by Dr. Alexander Fleming in 1928, when he noticed areas of inhibited bacterial growth around the mold, which had contaminated a petri dish of Staphylococcus aureus. A team of researchers led by Dr. Howard Florey later purified the penicillin compound and developed a method for large-scale production. By 1944, penicillin was being mass-produced and commercial production methods refined. It was a powerful tool during WWII, drastically reducing deaths from infected wounds and surgical procedures. Finally made broadly available to the public in 1945, penicillin was heralded as a “magic bullet,” capable of curing a wide variety of bacterial diseases. For an excellent history of the discovery and development of penicillin, I recommend the book The Mold in Dr. Florey’s Coat: The Story of the Penicillin Miracle, by Eric Lax.

 

Just 4 years later, strains of bacteria resistant to penicillin began to appear, spurring a search for alternatives. Following the penicillin model, researchers turned to other microorganisms for potential antibiotic substances. Soil bacteria provided a rich reservoir for such compounds, leading to the discovery of antibiotics such as streptomycin, erythromycin, and cephalosporins. But carelessness, complacency, and overuse of antibiotics allowed the pathogens to fight back, developing ways to resist these new drugs and landing us in our current predicament, facing dangerous strains of bacteria resistant to almost all available antibiotics, such as MRSA (methicillin-resistant S. aureus), MDR-TB (multi-drug-resistant Mycobacterium tuberculosis), and Neisseria gonorrhoeae. Only a small percentage of soil bacteria – approximately 1% - are able to grow under normal laboratory conditions, and with this reservoir seemingly exhausted, biochemical laboratory synthesis efforts failing, and no new antibiotics in the pipeline, the need for new antibiotic candidates is obvious.

 

One team of researchers decided to go back to the soil. In an exciting paper published in Nature this month, Ling et al. describe the development of a novel method for growing previously uncultivable soil bacteria, leading to the discovery of a new antibiotic they have called teixobactin. To grow the finicky soil bacteria, a sample of soil was diluted and distributed into a multichannel device called an iChip so that each channel contained only one bacterium. The channels were covered with semipermeable membranes to keep the bacteria in but allow exchange of nutrients and growth factors between the channel and the environment. The iChip was then returned to the original soil from which the sample was taken, creating growth conditions highly similar to the bacteria’s native environment. This method increased the number of soil bacteria that could be cultured from 1% to nearly 50%. Even better, once a colony is established in the iChip, many of the bacteria can then be grown in a laboratory setting.

 

The researchers screened extracts from 10,000 isolates obtained by this method for antimicrobial activity against S. aureus and identified a new protein compound produced by the Gram-negative organism Eleftheria terrae, which they named teixobactin. Teixobactin showed potent activity against M. tuberculosis and Gram-positive pathogens such as Clostridium difficile (which causes intestinal infection sometimes referred to as “C. dif”), Bacillus antrhacis (which produces the causative agent of anthrax), and S. aureus, including drug-resistant strains. Unfortunately, it was not effective against Gram-negative bacteria. Teixobactin showed no toxicity against mammalian cells in culture, and effectively cleared S. aureus and Streptococcus pneumoniae infections in mice.

 

Through several biochemical investigations, the researchers determined that teixobactin inhibits production of the bacterial cell wall by binding to highly conserved cell wall building blocks. Without a cell wall, bacterial cells lyse, spilling their essential contents into the environment. Other antibiotics, including penicillin, that inhibit the cell wall target its protein components. One mechanism of antibiotic resistance, known as target modification, results when these protein components, encoded in the bacterial DNA, acquire changes from random DNA mutations that alter the antibiotic target site, preventing antibiotic recognition and action. But teixobactin recognizes a lipid (fat) molecule, suggesting it could be less likely that resistance will develop in this manner. Excitingly, growth of S. aureus and M. tuberculosis on low doses of the drug and passage of S. aureus in the presence of subinhibitory concentrations for 27 days did not result in resistant isolates. In contrast, resistance to the antibiotic ofloxacin began emerging after only 3 days of serial passaging. (Research note: Oflaxacin targets DNA gyrase, an important enzyme in DNA replication and transcription. It would have been nice to see the serial passaging experiment done with penicillin and vancomycin, the antibiotic the researchers compare teixobactin to throughout the paper, as this would have provided control data related to other cell wall targeting antibiotics.) The potent effectiveness, lack of observed toxicity, and failure of immediate resistance development make teixobactin a good candidate for a new antibiotic.

 

These findings have been well celebrated in the media, with the suggestion that teixobactin might be a new “magic bullet”, its “resistance to resistance” finally giving us the upper hand in the battle against antibiotic resistance. It is important to keep in mind, however, that this drug is not effective against Gram-negative bacteria, which have a second membrane that protects the cell wall components which teixobactin targets. Thus, multi-drug resistant strains of pathogens such as E. coli, Pseudomonas aeruginosa, and N. gonorrhoeae are left to wreak havoc in the clinic. More importantly, claims of teixobactin’s “resistance to resistance” are a bit premature. Target modification is only one mechanism by which bacteria can gain antibiotic resistance. Other mechanisms include the acquisition of an enzyme that destroys or modifies the antibiotic, alteration of cell metabolism to avoid use of the product or pathway that the antibiotic targets, changes in cell wall composition or structure that keep the drug out of the cell, or use of an efflux pump, a cellular machine that can recognize and pump out antimicrobial compounds. While some of these mechanisms are more complex and may require exchange of DNA with other bacteria to acquire, all are possible. Development of resistance by serial passaging of a single strain in the lab is much different than within a human patient, where interactions with other pathogens and the normal flora (the bacteria normally found on and in the human body) are plentiful, and the presence of other antimicrobial compounds and alternative nutrient sources create a complex environment that could have significant effects on the development of resistance. There is evidence that genes for antibiotic resistance can be transferred among bacterial species, including those of our normal flora, in vivo.

 

The authors do acknowledge that resistance may develop, but assert that it would likely take several decades, citing the 30 years it took for development of resistance to vancomycin, which works by a mechanism similar to teixobactin, as an example. The comparison of the development of vancomycin resistance to that of other antibiotics, however, isn’t entirely fair. When vancomycin was first introduced, its relatively high toxicity and low efficacy kept it as an antibiotic reserved only for patients with allergies to β-lactams (such as penicillin) or resistant infections. In the early 1980s, as resistance to other antibiotics became more prevalent, vancomycin use spiked, and was followed by the development of resistant strains by 1986. Thus, the case of vancomycin resistance should actually serve as a warning: should teixobactin prove a viable antibiotic, careless overuse will quickly relegate it to the ever-growing pile of ineffective antibiotics.

 

Still, the significance of these findings should not be overlooked or understated. Ling et al. have provided us with the first truly promising antibiotic candidate in many years. Perhaps more importantly, they have developed a method for growing bacteria previously uncultivable in the lab, not only expanding the pool of available antibiotic candidates, but also creating a tool that could prove revolutionary in microbiology, ecology, and environmental research. We should be hopeful that teixobactin is safe and effective in human trials, and that either it can be modified to be effective against Gram-negative pathogens or that the iChip method reveals another compound as potent as teixobactin for their treatment. But we must also be responsible and cautious, so as not to squander these precious new drugs and hasten an era of untreatable bacterial diseases.

 


MRSA vaccine

The Hunt for the Holy Grail: A Potential Vaccine against MRSA

 

By Elizabeth Ohneck, PhD

Vaccines represent the “holy grail” in prevention and treatment of infectious diseases. Effective vaccines have allowed the eradication of small pox and contributed to drastic declines in cases of diseases such as polio, measles, and pertussis (whooping cough). As bacterial pathogens become more resistant to a broader spectrum of antibiotics, the desire to develop vaccines against these offenders to prevent disease altogether heightens.

 

Staphylococcus aureus is a common cause of skin and skin structure infections (SSSIs), as well as post-surgical and wound infections. SSSIs, which frequently present as abscesses in the upper layers of skin tissue, can serve as sources of more serious infections with high mortality rates, such as pneumonia, endocarditis, and bloodstream infections, when the bacteria break through the upper layer of tissue and invade other sites of the body. With the high prevalence of methicillin-resistant S. aureus (MRSA) depleting our antibiotic arsenal, S. aureus infections have become difficult to treat, spurring intense investigation into vaccine development.

 

A group from UCLA recently developed a potential vaccine, NDV-3. This vaccine is actually based on a protein from the fungal pathogen Candida albicans, which causes diseases such as thrush and yeast infections. The C. albicans protein is similar in structure to S. aureus adhesins, proteins on the bacterial surface that allow the bacterial cell to stick to host cells. In preliminary studies, the NDV-3 vaccine was shown to be protective against both C. albicans and S. aureus. In a recent paper in PNAS, Yeaman et al. examine in detail the efficacy of this vaccine in MRSA SSSI and invasive infection.

 

To determine the efficacy of the NDV-3 vaccine in prevention of S. aureus SSSIs, the researchers vaccinated mice with NDV-3, and administered a “booster shot” 21 days later. Two weeks after the booster, the mice were infected with S. aureus by subcutaneous injection, or injection just under the skin, to induce abscess formation. Abscess progression and disease outcomes were then monitored for 2 weeks.

 

Abscess formation was slower and the final size and volume of abscesses were smaller in vaccinated mice compared to control mice. In addition, mice vaccinated with NDV-3 were able to clear S. aureus abscesses by 14 days after infection, whereas abscesses in control mice were not resolved. Using a S. aureus strain expressing luciferase, a protein that emits light, the researchers were able to watch proliferation of the bacteria within the abscesses by measuring the strength of the luciferase signal. Vaccination with NDV-3 resulted in a significantly weaker luciferase signal than in unvaccinated mice, indicating NDV-3 vaccination prevents growth of the bacterial population. This finding was supported by a decrease in the number of CFUs (colony-forming units), an estimate of the number of viable bacteria, isolated from abscesses of vaccinated versus unvaccinated mice. Importantly, the researchers conducted these experiments with 3 distinct MRSA strains and observed similar results for each. Together, these findings demonstrate that while the NDV-3 vaccine does not completely prevent SSSIs under these conditions, vaccination can significantly reduce severity.

 

As skin infections can often serve as a source for more serious disseminated infections, the researchers also examined the effect of NDV-3 on the spread of S. aureus from the original site of infection. While control mice developed small abscesses in deeper tissue layers, vaccinated mice showed little to no invasion of infection. Additionally, significantly fewer bacteria were found in the kidneys of vaccinated mice compared to control mice, indicating NDV-3 can prevent the spread of S. aureus from skin infection to more invasive sites.

 

To examine how NDV-3 was stimulating a protective effect against MRSA, the researchers measured the amount of molecules and cells important for immune response to MRSA in vaccinated and unvaccinated mice. Abscesses of vaccinated mice showed a higher density of CD3+ T-cells and neutrophils, as well increased amounts of the cytokines, or immune cell signaling molecules, IL-17A and IL-22. Vaccinated mice also showed higher amounts of antibodies against NDV-3, as well as increased production of antimicrobial peptides, small proteins with antibiotic activity produced by host cells. Thus, the NDV-3 vaccine helps encourage a strong immune response against MRSA.

 

The NDV-3 vaccine was recently tested in a phase I clinical trial and found to be safe and immunogenic (i.e., stimulates an immune response) in healthy human volunteers. While the vaccine in it’s current form doesn’t prevent S. aureus infections altogether, it could help make infections easier to treat by slowing bacterial growth, preventing spread to other tissues, and boosting the host immune defenses. Further research on this vaccine may also lead to a form that is more protective and can better prevent infections.

 


Scientists Letters to Santa Revealed

 

By Elizabeth Ohneck, PhD and Padideh Kamali-Zare, PhD

For many children, Christmas morning was the culmination of months of eager anticipation, the reward for a year of good behavior, the moment the generosity (or perhaps judgment) of Santa Claus was finally revealed. There was undoubtedly gleeful satisfaction (Lady scientist Legos? YES!), and sighs of disappointment (When will Santa bring me a pony? I’ve been asking for 29 years!) In the afterglow of the holidays, these children (and, let’s face it, many adults) are carefully inventorying their holiday spoils against their submitted wish lists, and already composing their next letters to Santa.

Scientists also have wish lists they cultivate year-round, although the nature of the items differs greatly from that of hopeful children (except Lady Scientist Legos; those definitely belong on both lists). While the magic of Santa Claus has long since been lost to the logic of adulthood and science itself, as we easily overthink the constraints of physics and time that would make flying around the world in a sleigh pulled by reindeer delivering toys to every child in one night impossible, we might still find ourselves caught up in the holiday spirit, hoping for a Christmas miracle. So, for a moment, let’s suspend this practicality. Let’s pretend that there is a Santa Claus for science, a jolly, magical figure who flies around the world granting the wishes of labs one night a year. What, exactly, would scientists ask for? And would Science Santa Claus deliver?

Below, a few scientists offer the letters they submitted to Santa this year.

 

Dr. Claus,

As the holiday season approaches, it is time to submit our annual progress report to the Naughty or Nice committee for review. Herein, we provide evidence for the inclusion of our lab on the Nice List, and a list of proposed items that would add to the continued success of our group.

 

This year, we have worked collectively over 500 hours each week, including late nights, early mornings, weekends, and holidays. We have published or contributed to the publishing of 10 peer-reviewed papers. In addition, we have given several successful poster and oral presentations. One of our postdocs successfully obtained a faculty position. And we hosted one heck of a department mixer. Taken together, we believe these data qualify our lab for the Nice List. As such, we would like to request the following holiday gifts:

 

  1. A first author paper. Ok, 9 first author papers, if we’re being perfectly honest. But we’d be happy with 4. You can team us up for some co-first author publications.
  2. An automated plate spreader, an automated colony counter, a machine that automatically does all the washes for ELISAs in a 96-well plate… basically anything automated. It’s not that we’re lazy (well, maybe a little). We’re just trying to be more efficient with our time and energy. We could do bigger experiments and fit more experiments into a day. (On second thought, we might re-think this one. Hold off for a bit. We’ll get back to you.)
  3. Repeat pipetters. Or, at the very least, a fully functional, easy to use, consistently accurate P10 multichannel pipette. Such an item would greatly increase both the precision and accuracy of our results, slow the inevitable development of carpal tunnel syndrome, and probably prevent that one postdoc from having a nervous breakdown (you know which one we’re talking about).
  4. Stuff to work. Particularly cloning, transduction, qPCR, and getting repeatable results from that one stupid experiment.
  5. The PI would like a 24-hour lab.

We are aware that funding is tight, which may prevent the granting of more than one request per lab. Should this be the case, you may disregard the above list in exchange for only the following:

Please, for the love of science, do NOT allow #5 to happen. Ever.

Thank you for your time and consideration. We wish you safe travels this holiday season.

 

Best regards,

The Microbiology lab

 

 


 

Dear Santa,

I know you must be very busy this time of the year so I make it short. Below is the list of my requests to you that would appreciate a lot if you take a look:

 

  1. Please provide some different ways of funding for science so the PIs are not so much under pressure of getting data, publishing papers and applying for grants. There is something seriously wrong with such an ecosystem that makes everyone at any level unhappy. And beyond that, it makes the science world full of discoveries that are in response to “call for proposals” and not scientist’s inner motives to “discover the unknown”. This is not the way science should be. You agree?

 

  1. Please send scientists, once in a while, messages that include an overview of their projects so they don't get lost in details. Something like a map that shows the big picture! And please help them read the map if it's not in a nerdy language.

    3. In the end scientists wanted to make a difference that's why they chose science among all other much-better rewarding career paths. Please help them find their individual ways to do so. Still most scientists believe science as a life style, as a way of thinking and not a job! Don’t let them become disappointed... PLEASE!

 

Thank you very much and looking forward to seeing some magical action from you this year! Yes! You can! Do it!

 

-Padideh Kamali-Zare

 

Did you have a science holiday wish list? What did you ask Science Santa for? Did he (or she) deliver? You’ll be happy to know the Microbiology Lab made the Nice List and received TWO new, state-of-the-art P10 multichannel pipettes. They’re still waiting to see whether their experiments have started working. And seriously hoping the 24-hour lab request was overlooked.


Crafty Pathogens Share the Cost of Resistance

 

By Elizabeth Ohneck, PhD

 

Bacteria have been evolving with us humans since we first came into being. Some of these microorganisms have become our indispensable partners, aiding our digestion, helping the development of our immune systems, and protecting us from less friendly bacteria. Others, in this less-friendly category, cause a vast number of illnesses and diseases, and have evolved to more insidious organisms, developing ways to outsmart our immune systems and resist antibiotics to survive within us and spread to new hosts. Pathogens like Neisseria gonorrhoeae, Staphylococcus aureus, and other multi-drug resistant “superbugs” have been continuously acquiring clever adaptations to protect themselves from our immune and antibiotic arsenals, leaving few options for patient treatment.

 

Many of the mutations that protect pathogenic bacteria from antimicrobial factors, however, come at a cost. Most antibiotics target cellular parts and processes essential to bacterial survival. To block antibiotic recognition of or action on these targets, bacteria must mutate critical cell components, which can reduce fitness, or the ability to grow and reproduce efficiently. Such fitness costs cause these mutants to grow more slowly than their wild-type, or “normal,” counterparts and other microorganisms present in the environment; thus, it is possible these mutants may not persist, as they might lose the battle for space and resources to their more fit opponents. In addition, some of these mutations decrease the ability of bacteria to produce virulence factors, which are critical in causing disease. Yet bacteria with mutations in important cell components are frequently recovered from patients with serious illness. How are these mutants able to successfully survive within the human host and cause severe disease?

 

A team from Vanderbilt University sought to answer this question with research published in Cell Host and Microbe in October. Hammer et al. examined Staphylococcus aureus small colony varients (SCVs), which are often isolated from patients with chronic disease and are resistant to multiple antibiotics. SCVs contain mutations in important biosynthetic pathways, resulting in slow growth and limited virulence factor production. Hammer et al. chose two primary mutants for their study: one unable to produce heme, and one unable to produce menaquinone, both of which are essential metabolites for bacterial respiration. Both mutants showed reduced growth rate and decreased ability to cause bone destruction in a mouse model of osteomyelitis. These defects were overcome by providing the metabolites during growth, demonstrating it is the inability of these mutants to produce the metabolites that causes their reduced fitness.

 

Interestingly, growing these two mutants together restored their growth and ability to cause bone destruction, suggesting the mutants could use the missing metabolite produced by the other mutant for normal growth and efficient virulence factor production. Surprisingly, growth of the mutant unable to produce menaquinone with another human pathogen, Enterococcus faecalis, also restored growth of the mutant, demonstrating that SCVs can use metabolites not only from other S. aureus, but from other bacterial species. Most importantly, the researchers demonstrated that these interactions can occur in patients during infection. The team isolated bacteria from the upper respiratory tract of patients with cystic fibrosis and found several bacterial species, including Staphylococcus epidermidis and Streptococcal species, that enhanced growth of the SCV mutants unable to produce heme, menaquinone, or both. In addition, they found many distinct SCVs that could rescue the growth of the heme and menaquinone mutants, as well as one another. These findings provide evidence that antibiotic resistant mutants can survive and cause disease despite fitness defects by borrowing factors important for growth from the surrounding microbial community, including the “friendly” bacteria that normally reside with in us, turning friends into foes.

 

It’s important to note that slow growth is an important factor in the antibiotic resistance of SCVs. When the heme or menaquinone synthesis mutants were rescued by growth with other strains, they became more sensitive to the antibiotic gentamicin, clearly demonstrating the trade-off between fitness and resistance. It’s plausible that wild-type S. aureus and SCVs work together for efficient, resistant infection. Wild-type strains can establish infection and increase the overall population, while the development of SCVs ensures population survival in the face of antibiotic treatment. The ability to use metabolites from other microorganisms is a clever evolutionary adaptation to compensate for the sacrifice in fitness made for the gain of antibiotic resistance, and an important consideration in the treatment of patients with bacterial infections and the development of new drugs.


Should postdocs jump the academic ship

Should Postdocs Jump The Academic Ship?

By Elizabeth Ohneck, PhD

 

A recent series of articles on NPR called “Science Squeeze” painted a rather abysmal picture of the current state of scientific research, from lack of funding, to job shortages for young scientists, to stories of scientists “giving up,” leaving academia for other, though not always better, ventures. The article “Too Few University Jobs for America’s Young Scientists” features interviews with a few postdocs at NYU about their current situations and their prospects for an academic future. Their responses are not altogether negative, but are far from resoundingly positive. The article also hints that PhDs may be better off pursuing careers outside of academia, a path that more and more graduate students and postdocs are beginning to take. To get a broader perspective on how the current scientific research climate is affecting the career trajectories of postdocs, I talked with several postdoctoral scientists at varying stages of their careers about their reactions to the NPR series and how the issues presented affect their outlook for the future.

 

Not all postdocs are ready to jump the proverbial ship when it comes to pursuing an academic career, despite awareness of the hurdles ahead. Dr. Randy Morgenstein, a senior postdoc an Ivy League university, pointed out the limited scope of the NPR series, which focused on only a couple specific universities and individuals whose situations were particularly dire, and felt the articles portrayed the academic environment in an overly gloomy manner without actually addressing the overarching flaws in the system. “The articles make a pity party out of 1 or 2 places or people without making me feel the system isn’t working. So overall, I think they might have presented the state of scientific research in this country in too much of doomsday state… A better approach would have been to make me feel bad for society because good scientists are unable to get grants and do research.” He acknowledges, however, the truth of difficulties in obtaining grants and the competition for an extremely limited number of faculty positions. Despite these factors, he is persistent in pursuing a career in academia. “Academic research gives you the most freedom to pursue the research you are interested in. I like that aspect of it and think it is worth the risk to pursue.” When asked how one might overcome the obstacles in funding and faculty position availability, he responded, “I think anyone becoming a PI has to be self-confident almost to the point of arrogance, and therefore think that it’s the other people who won’t be able to get grants.  I do not think I am doing anything special to overcome these difficulties. Same as everyone else, I am trying to publish the best papers that I can, hopefully on a topic that people think is worth funding in the future.”

 

What about those who have successfully made the transition from postdoc to assistant professor, who might provide hope for those postdocs still set on an academic track? Dr. Francis Alonzo III is one such scientist, having recently obtained an assistant professor position at Loyola University Chicago. He chose to pursue an academic career because of his love of science and education, and credits his success to persistence, passion, drive, and curiosity. In addition, he added, “I really just could not see myself doing anything else. Because of that, I knew what my goals were from the start and worked as hard as I needed to get there.” But he feels that the NPR series accurately portrayed the state of scientific research, and this reality of uncertain funding means securing an assistant professorship doesn’t necessarily relieve his apprehension. “I do still love engaging in the scientific process and being involved in training and educating students,” says Dr. Alonzo. “And I still get a lot of joy coming into the lab everyday. However, I am considerably more apprehensive about what the future holds. In particular because I am just gearing up to submit my first larger grants and I have no idea how my ideas will be perceived.”

 

There are, however, many postdocs struggling to find jobs, and many who are turning away from academia in hopes of finding more opportunities. Dr. Bree Szostek Barker, a junior postdoc at the University of North Carolina, originally planned to pursue an academic career, but has recently been looking into possibilities outside of academia. She feels the NPR series actually understated the severity of the problems with funding and the job outlook in academic research. “The articles' focus on a few universities, namely Baylor and Virginia, makes it appear that this is an issue isolated to a portion of schools/institutions/researchers that overextended during good times,” she said. “Every university and the vast majority of PI's are feeling this, with the exception of the select few who are immeasurably successful.” The lack of job security created by limited academic positions and uncertain funding resulting from the current system of the academic research sector has pushed her to explore alternative careers. But securing a job in the private sector or a job that is not research-based has turned up its own set of problems; specifically, PhDs and postdocs seem to be missing relevant experience in the eyes of recruiters for these positions. For this reason, Dr. Szostek Barker disagrees with the assertion made in “Too Few University Jobs for America’s Young Scientists” that there are abundant jobs for PhDs outside of academia. “The fact is the number of jobs seeking a PhD with no experience in their industry is low and to pretend otherwise is offensive. And the jobs that do arise are so heavily competed for that the chances of getting the position is extremely slim,” she said, adding, “Unfortunately academia doesn't count as ‘experience’ for anything except academia.”

 

It seems that the NPR series may have portrayed academic research in too much of a doom-and-gloom state, but also didn’t delve deep enough into the overarching problems in the structure of the scientific research sector. Funding is difficult to obtain, and faculty positions are few. Yet there are success stories to be found, and there are postdocs maintaining a hopeful outlook in spite of the enormous obstacles they face. But the system in which each PI trains multiple successors is unsustainable, and so to overcome job shortages, many postdocs are looking outside of academia for careers. What is not acknowledged in this series is that these non-academic jobs may be equally as hard to come by. Altogether, the consensus is that the system is flawed. But how do we fix the system? More money alone is likely not the answer. What contributes to one’s success on the academic track? Plenty of bright, passionate, confident, motivated scientists end up leaving academia, unable to secure funding, or worn down by the fierce competition, so what factors, both personal and academic, allow some to flourish while forcing others out? And finally, how can we better prepare PhDs for jobs outside of academia? The NPR series has brought these issues to the public eye. Hopefully this exposure will drive further discussion and a search for solutions to ensure a future full of happy, fulfilled scientists and prolific, productive scientific research.

 


When Women Reach for the Stars

By Elizabeth Ohneck, PhD

 

In the second grade, I wrote a report for class about Jane Goodall. Bright, bold, independent, and inquisitive, she became my instant personal hero. I looked up to her, wanted to be just like her. (Who doesn’t want to run away to the jungle and befriend wild animals? Some days this still sounds like a good idea.) And so, a scientist was born. But throughout the rest of my education, there was a distinct lack of female heroes and role models. Of course we touched upon the greats: Susan B. Anthony, Harriet Tubman, Jane Austen, Maya Angelou. But where were the great female scientists? The history of the natural sciences, like the natural sciences themselves until recently, was heavily male dominated. Whom could budding young female scientists look to for inspiration?

 

Encouraging girls and young women to pursue their interests in STEM (science, technology, engineering, and mathematics) is currently a topic at the forefront of our collective societal mind. The invention of toys like GoldieBlox and Lego’s release of a line of female scientist characters exemplify responses to the demand to find ways to teach gender equality in education and careers at an early age. Aside from toys, how else can we encourage girls to delve into STEM fields? Can we find role models whose stories inspire their dreams?

 

In June, we can celebrate two very important women: Valentina Tereshkova, the first woman to journey to space, and Sally Ride, the first American woman in space. Their inaugural trips took place almost exactly 20 years apart, Valentina’s in June of 1963, and Sally’s in June of 1983. Their enthusiasm, bravery, and willingness to take risks provide inspiration for women of all ages (and men too!).

 

Valentina Tereshkova was born in 1937 in Maslennikovo, Russia. Although she had to drop out of school at the age of 16 to begin working in a factory, she continued her education through correspondence courses. Around the age of 22, she became an enthusiastic skydiver and an accomplished parachutist. In the early 1960s, in the midst of the “space race” between the United States and the Soviet Union, the Soviet space program was looking to collect data on the effects of space flight on the female body. When Valentina volunteered to serve as the female astronaut, the Soviet space program took notice of her parachuting skills. She had no pilot experience, but as the flight was to be run by automatic navigation, such experience largely unnecessary. Of more importance was the ability to handle the ejection at 20,000 feet required upon re-entry into earth’s atmosphere, for which Valentina was well-prepared, thanks to her skydiving activities. Thus, Valentina was accepted into training in 1962.

 

On June 16, 1963, the Vostok 6 launched with Valentina aboard, making her the first woman to enter space. She completed 48 orbits of the earth in 71 hours, more time than all of the U.S. astronauts combined had spent in space at that point, and returned to earth on June 19, landing near Karaganda, Kazakhstan. In recognition of her bravery and accomplishment, she was awarded both the Order of Lenin and the Hero of the Soviet Union awards. While she would never return to space, Valentina went on to become a member of the USSR’s national parliament, and served as the Soviet representative to numerous international women’s organizations.

 

It would take the U.S. 20 years to catch up in regard to sending a woman into space, but when they were ready, Sally Ride was up for the job. Sally was born on May 26, 1951 in Los Angeles California. She studied both English and Physics at Stanford University, and went on to earn her Master’s and Ph.D. in physics. In 1978, Sally responded to an advertisement in the Stanford student newspaper, seeking applicants for the NASA astronaut program. Out of thousands of applicants, 35 were selected, with only 6 being women, but among them was Sally Ride. Prior to her space flight, she completed rigorous training, served as part of the ground crew for two space shuttle flights, and contributed to the development of a robotic arm used by the space shuttle.

 

On June 18, 1983 Sally became the first American woman in space as part of a 5 person crew aboard the Challenger. She would return as part of another Challenger mission the following year, for a total of 343 hours in space. Although she was scheduled to take a third trip, the flight was cancelled following the explosion of the Challenger on January 28, 1986. Sally was appointed as part of the commission to investigate the accident.

 

Following her time at NASA, Sally became the director of the California Space Institute and a professor of physics at the University of California, San Diego. She received numerous awards for her contributions in the field of space exploration, including the NASA Space Flight Medal and induction into both the National Women’s Hall of Fame and the Astronaut Hall of Fame. In addition, Sally was passionate about encouraging girls and young women to pursue careers in science, math, and technology. She founded Sally Ride Science, a company that creates educational science programs and publications for elementary and middle school students, and wrote several books for children about space exploration and the solar system.

 

Valentina Tereshkova and Sally Ride challenged the status quo and bravely pursued their passion, unafraid to face skepticism and step into a male-dominated field. They both went on to use their experiences and the status they gained to help other women follow their own dreams. Both Valentina and Sally literally reached for the stars. Their stories serve as examples to show our daughters, nieces, sisters – all women – that they can do the same.


overstated science

Sensationalized Science

 

By Elizabeth Ohneck, PhD

 

In a recent Letter to Nature, researchers from the Scripps Research Institute announced that they had successfully engineered a bacterium that could recognize and replicate DNA containing an unnatural base pair (UBP). Their publication, entitled “A semi-synthetic organism with an expanded genetic alphabet”, demonstrated that E. coli could recognize, take up, and utilize man-made nucleotides to reproduce a plasmid containing a base pair of the synthetic nucleotides, faithfully replicating the UBP for over 20 generations (read more about it in our post about the paper).

 

The findings presented by the authors are incredibly exciting and have huge implications for future research in genetics, microbiology, and medicine. The presentation, however, is concerning. The authors refer to their strain of E. coli as “semi-synthetic.” Such a term could, for non-scientists (or even the scientist with a highly active imagination), conjure up images of some half bacterium-half robot, a sort of Frankenstein’s monster bacterium manufactured by man in the lab. What they actually have is a strain of E. coli carrying two plasmids, one that expresses an algal transporter able to import the synthetic nucleotides, and one containing the UBP. The introduction of plasmids into bacteria is a staple of biological research, and non-native proteins are regularly expressed in microorganisms from E. coli to yeast for countless research and industrial purposes. Are these microorganisms, then, also considered semi-synthetic? Referring to this E. coli strain as such actually does the findings a disservice, as part of what makes this report so exciting is that a common organism could recognize and utilize synthetic nucleotides with its own DNA replication machinery. The idea of an “expanded genetic alphabet” is also somewhat of a stretch, as the second plasmid contained a single UBP but was otherwise composed of canonical, naturally occurring A-T/G-C base pairs. This single UBP wasn’t utilized in any biological or genetic function; it was merely maintained during plasmid replication. Can we consider this UBP a true expansion of the genetic alphabet if it is not interpreted for inclusion in a bacterial function? Do the lofty terms used in the title sensationalize the story in an effort to attract an audience?

 

For trained scientists, this issue may seem minor; after all, would anyone outside of the research sector truly read or pay attention to this paper? If the research results become a news story, they might. In fact, the bigger problem is the communication of this research to the general public by the media, which further sensationalized the story. CNN even published an article entitled “New life engineered with artificial DNA.” One merely needs to glance through the comments section of the online article to understand the backlash of such a claim. Is this organism really “new life?” Is “artificial DNA” perhaps an overstatement?

 

The current climate of public attitude toward health science and genetic research is bitterly divided. Consider, for example, the well-publicized, acrimonious debates over vaccination, pharmaceuticals, and GMOs. Articles that imply scientists are "playing God" by "creating new life" only increase suspicion and inflame anti-science sentiment among groups already wary or contemptuous of health and science research. While it’s important to draw readers and sell stories, sensationalizing the science inhibits fair dialogue over the subject and detracts from the value of the scientific discovery.

 

The advancement of science needs public support – financially, politically, and even in terms of morale – which we can only gain through transparency and the communication of accurate information in the interest of educating the public. As research scientists, good communication starts with us. We have the responsibility to ensure our findings are clearly and truthfully conveyed to any audience, including among the research community. In turn, it is up to science writers and journalists to ensure the appropriate communication of scientific research to the public, in a manner intended to do more than sell stories. Science, itself, is sensational. Let’s not allow fabricated drama to take away from the excitement and wonder of scientific discovery.


The Discovery of HIV: A Tale of Two Scientists

 

By Elizabeth Ohneck, PhD

In the early 1980s, scientists were struggling to find the cause of a new, rapidly spreading disease called Acquired Immune Deficiency Syndrome, or AIDS. At the time, few thought that a virus could cause this devastating disease. But the work of two labs, that of Robert Gallo at the U.S. National Cancer Institute, and that of Luc Montagnier at the Pasteur Institute in France, would lead to the discovery of the novel human retrovirus HIV in May of 1983 and later establish this virus as the cause of AIDS. They could not, however, predict the drama that would unfold from their discoveries.

 

Both labs originally sought to identify a retrovirus associated with cancer in humans. At the time, they were considered “old fashioned” in this pursuit. Starting in the late 1970s, the general attitude was that microbes no longer posed a major health threat in industrialized countries. In addition, research had yet to uncover a retrovirus that infected humans, much less one that caused cancer.

 

Gallo’s research led to the discovery of interleukin-2, a factor that stimulates T cell growth, allowing T cells to be grown in culture. This method laid the groundwork for Montagnier’s team to recover reverse transcriptase, a retroviral enzyme, from T cells of human cancer patients, providing the long-sought evidence that retroviruses do infect humans and might be associated with cancer. Perseverance paid off when Gallo’s group isolated the first human retrovirus from a patient with T cell leukemia, which they named human T cell leukemia virus, or HTLV.

 

Nevertheless, agents such as fungi, chemicals, and autoimmunity were considered more likely causes of AIDS. But Gallo and Montagnier saw several clues that a virus was to blame. The hallmark of AIDS was a decrease in the levels of T cells carrying the surface antigen CD4, suggesting the causative agent might specifically target CD4+ T cells. In addition, epidemiology studies indicated AIDS was transmitted through blood, sexual activity, and from mother to infant. HTLV exhibited these same characteristics, so they believed HTLV was a likely candidate.

 

Montagnier’s lab began searching for retroviruses from patients with AIDS. While they were able to recover retroviruses from the cells of these patients, the viruses did not react with antibodies against HTLV. Upon comparing electron micrograph pictures of the new virus to HTLV, it was clear to Montagnier that the virus from AIDS patients was different. Montagnier’s group termed this virus LAV. Meanwhile, Gallo’s lab was conducting its own search, and isolated two forms of HTLV from patients with AIDS. One exhibited unusual characteristics, which they called an “aberrant” form. They would later realize that these patients were actually doubly infected with HTLV and HIV.

 

The two research teams had collaborated extensively, so Gallo and Montagnier agreed to publish their findings together in the May 20, 1983 volume of Science. But whether HTLV or LAV actually caused AIDS was still unclear. In 1984, Gallo’s group announced the isolation of a virus related to but distinct from HTLV, termed HTLV-IIIB, from a pooled collection of samples from AIDS patients. This virus could be continuously cultured, allowing thorough study, a problem Montagnier had not been able to overcome with LAV. Gallo also provided convincing evidence HTLV-III viruses in fact caused AIDS, and the HTLV-IIIB isolate was used to develop a blood test to ensure purity of blood bank supplies were uncontaminated and test patients for the presence of the virus.

 

HTLV-IIIB, however, was strikingly similar to an isolate Montagnier’s group was studying, LAI, that also grew robustly in culture, identified before HTLV-III. Such similarity between different isolates would be unusual, as these viruses were found to be highly variable. When it turned out these viruses were essentially the same, an argument ensued. The two labs had exchanged multiple isolates. Had Gallo inappropriately used the Pasteur Institute isolate for the development of the blood test? Who should get credit for the discovery of this new virus? Should the French group have rights to the blood test patent?

 

Finally, President François Metterrand of France and U.S. President Ronald Reagan met to resolve the issues between their scientists and governments. In 1987, it was agreed that the scientists would share the prestige of the discovery and the patent profits of the blood test equally. The names LAI and HTLV-III were exchanged for human immunodeficiency virus, or HIV. Motagnier was credited with its discovery, as he was the first to isolate a pure culture of the virus. Gallo was credited for demonstrating conclusively that HIV causes AIDS. In 1993, scientists at Roche analyzed archived samples of viruses from both labs and discovered that a sample of LAV given to the Gallo’s group by Montagnier, had been contaminated with LAI, identifying the cause of the confusion and officially clearing Gallo of any misconduct. Tempers cooled, and in 2002 Montagnier and Gallo published three papers, one co-authored by both scientists, reviewing the history of HIV/AIDS research and acknowledging the contributions each had made.

 

Unfortunately, the 2008 Nobel Prize in Physiology or Medicine did not reflect this compromise. The prize was awarded to Luc Montagnier and co-researcher François Barré-Sinoussi for the discovery of HIV, and was shared with Harald zur Hausen, who established the link between HPV and cervical cancer. As the Nobel Prize can be split among maximally three people, this meant Robert Gallo was left out. Had the selection committee chosen to focus only on HIV, Gallo almost certainly would have been included. This decision was met with some surprise; Montagnier himself stated the third recipient should have been Gallo.

 

Both scientists are quick to point out the astounding rapidity of HIV research. It took only 2 ½ years from its first identification to establish it as the causative agent of AIDS, and another 2 years to develop a commercially available blood test. In 1987,the first anti-HIV drug, AZT was introduced, soon followed by protease inhibitors and eventually the triple drug therapy used today that has saved countless lives. Despite some tumultuous times, the story of Gallo, Montagnier, and HIV serves as important demonstration of the power and necessity of scientific cooperation.


Which Came First: the Enzyme or Metabolism?

 

By Elizabeth Ohneck, PhD

Where did we come from? How did life originate? These questions are perhaps the oldest form of “existential crisis,” and questions that science has long sought to answer. The path from simple elements to complex biological systems was dependent on the development of self-organizing, self-replicating systems, as well as generation of metabolic pathways and the enzymes that drive them. Much work has been done to build a map of this evolution, but we are far from a complete understanding.

 

Metabolism is the group of chemical reactions required for life, the processes that build our DNA, our RNA, and the proteins and fats that comprise us, as well as break down molecules to provide the energy for these activities. These reactions occur within cells and are driven by proteins called enzymes. Many of these reactions are conserved among all life, from tiny bacteria, to plants, to animals, including humans, suggesting these metabolic processes are ancient and likely arose before life as we know it; in fact, the origination of these processes likely allowed the formation of life. The consideration of the origins of metabolic networks presents a chicken-or-egg scenario: which came first, metabolism or enzymes? In an exciting paper published in Molecular Systems Biology, Keller et al. provide evidence for the former, demonstrating metabolic-type reactions can occur in the absence of enzymes in an environment that plausibly mimics earth before life.

 

Keller et al. selected a series of compounds that serve as intermediates of two universal metabolic pathways: glycolysis, which breaks down the sugar glucose to release energy, and the pentose phosphate pathway, which converts sugars to ribose-5-phosphate, a building block of RNA and DNA. Using ultra-pure water and chemical preparations, they first dissolved a known concentration of each chemical in water and heated the solutions to 70°C, a plausible temperature for early earth ocean environments near heat sources such as thermal vents. After 5 hours, they examined the chemicals in the solutions by liquid chromatography-selective reaction monitoring, a highly sensitive technique to measure the types and amounts of chemicals in solution. They discovered that many of the compounds were converted to other metabolic intermediates, with the most common being pyruvate, an important branch-point metabolite that can be used to generate energy or converted to sugars, fatty acids, or amino acids.

 

The researchers then repeated this experiment in an “Archaen ocean mimetic” – a solution of salts and metal ions at concentrations likely found in early earth’s oceans, as determined from geological data. While the salts alone did not change the reaction outcomes, the addition of metal ions resulted in a greater number of conversions, including the production of ribose-5-phosphate and erythrose 4-phosphate, a precursor for the formation of amino acids. In further studies, the researchers demonstrated that iron, which would have been at high concentration in early earth’s oceans, was the key metal ion in driving the conversion reactions. Additionally, they showed that an anoxic, or low-oxygen, environment, as would have been the state of early earth, facilitated these reactions.

 

The conversion of metabolites mimicked enzyme-catalyzed metabolic reactions that occur within our cells. The researchers ruled out the possibility of contaminating enzymes in their reactions in several ways. First, they conducted these reactions at a temperature that, while plausible for the early earth ocean environment, is too high for most metabolic enzymes. Importantly, these reactions were not observed below 40°C, temperatures at which common metabolic enzymes would be functional. Second, critical cofactors, or small molecules required for the function of some enzymes, were absent. Third, the researchers stringently assured purity of their reaction mixtures through physical and chemical means, including filtering the solutions through a membrane with a very small size cut-off that would exclude complex proteins such as enzymes, repeating experiments in different types of reaction tubes, and adding organic solvents that would denature or inhibit enzymes.

 

Thus, Keller et al. effectively demonstrated that metabolic reactions critical to life that we know today to be catalyzed by enzymes can occur in the absence of enzymes under conditions that mimic the environment of earth before life. These reactions include the formation of molecules that form the building blocks of RNA, DNA, and proteins, of which all living organisms are comprised. Their findings provide support for the hypothesis that metabolic networks arose first, leading to the subsequent formation of RNA and enzymes, which would eventually give rise to self-replicating systems that would evolve into the first cells.

 

Many questions remain, perhaps the most prominent being: where did the original metabolite compounds come from? One possibility is based on the Miller-Urey experiment, published in 1953. In this experiment, researchers combined water, methane, ammonia, and hydrogen, thought to be the primary components of the early earth’s atmosphere, and applied high-voltage electrical pulses, which, surprisingly, generated the amino acids alanine and glycine. Subsequent research refined the reaction set up to more accurately mimic the environment of early earth and was able to demonstrate the creation of multiple essential biomolecules. One might imagine, then, that the elemental and atmospheric conditions of earth pre-life allowed the generation of complex molecules, which, in the low-oxygen, high-iron conditions, underwent chemical conversions, creating the first metabolic networks that in turn allowed the generation of life.

 

These hypotheses are, of course, just that: hypotheses. Whether the occurrence of such a chain of events can be conclusively proven is debatable. But studies such as the Miller-Urey experiment and the research by Keller et al. present thought-provoking findings that stimulate careful consideration of the incredible set of circumstances that lead to the generation of life. To imagine how simple elements combined to form the diversity and complexity of life on our planet today can be overwhelming and awe-inspiring. The study by Keller et al. provides an important piece in the puzzle of understanding our past.