Duke University | Howard Hughes Undergraduate Program

The 2009 Howard Hughes Undergraduate Fellowship is almost over. My roommates and I pack amidst the rush to finish our posters and eat our remaining food (which mostly entails googling and making recipes involving cinnamon raisin bagels). During this busy time, I’ve set aside a moment to ponder the foremost question in every college student’s mind: What do you picture as your career?

Well, how does one pick a career? Surely, we all strive for jobs that interest us. I would be extremely unhappy as a banker if I was only interested in phytoplankton biology, for example. Many people, especially women, also look for jobs that allow time for a family. On a deeper level, some people want a job they feel is important. If I felt my job was useless, unhelpful, or harmful to what I deem important, I would likely find my job depressing. Unfortunately, the real world isn’t usually so kind as to provide us a career that fits such ideal criteria, but one can always try.

So if I’m striving to find a job that’s interesting and important, I’d first better define what’s interesting and important to me.

My interests are pretty broad. I actually enjoy doing research; this summer has taught me as much. Despite all the grunt work, solving medical problems is an extremely stimulating job. I enjoy the company of the other lab scientists and even the concentration involved in bench work. Just as long as I remember to sleep and enjoy lab outside of life, I would enjoy a research job. I also delight in teaching. Two of my favorite high school activities were teaching piano and teaching chemistry through demonstrations. I love working with kids and people, and it’s great to see students get intrigued by and involved in what I teach. Sure, the occasional bad day and difficult student comes along, but that all part of life. As a whole, I enjoy teaching. A few other interests besides working with people and science include traveling, the environment, and nature.

One could write several papers and conduct academic debate as to what is important, but I’ll just give a brief outline of what’s important to me. I consider quality of life to be of the upmost importance. As one’s health contributes greatly to their quality of life, being a doctor is a job I would enjoy and believe important. However, both my motivations behind and doubts about becoming a doctor are far more complicated. In America, persons are so long-lived that doctoring should involve ensuring that a person’s passage from this life is as comfortable as possible. Unfortunately, modern medicine’s primary goal is still to keep persons alive as long as possible. As an American doctor, I’d like to help improve this and make end-of-life care a medical priority. However, the health care is difficult to navigate, and practices spend much time helping their patients through the health care system. Not to mention that many persons in this country do not have health care. As an American doctor, I’m not sure I would be prepared to work through the health care system here. I’ve always found that navigating the system and indeed most business policies is not my particular strength. Yet I don’t want to be providing services only to those who can afford health care. I spent most of my childhood without medical insurance, and my family and I would avoid seeing a doctor even when severely sick or injured. Thus, working to provide needy Americans with health care and improve America’s sincerely desperate system, rather than becoming a doctor, is a possible career.

Furthermore, there’s a whole world out there in need of health care. Joining programs such as doctors without borders is extremely appealing to me, but that’s a job that I can’t hold for a lifetime. Also, I consider the relationship between people and their environment to be incredibly critical to our health and the health of future generations. Working to help people coexist with their environment on both a scientific level and especially a policy level is extremely appealing, and I’d love to take classes to find out more about the environment.

In summary, my career could follow a number of paths, none yet quite defined. I hope to take advantage of the any opportunities around me to develop a career doing something interesting and important.

One final note: It seems there’s often a surprise element to everyone’s career. Very few people know their exact career goals growing up, and come to realize those goals perfectly. Rather, your opportunities often shape your career. So go for it! Take advantage of good opportunities around you gain experience and develop interests realistically. Don’t expect the perfect job to arrive on your doorstep after college. Rather, use every opportunity around you to develop your interests and skills, and maybe you’ll get a career you enjoy.
 

What a roller coaster ride! Here’s a couple lessons I learned this summer…

- If you don’t want to contaminate your cell cultures, spray everything perpetually with ethanol.
- What exactly defines a cancer.
- Why the cold room has a hole in the side.
- How to work a FACS machine (no, NOT a fax machine)
- Why not everybody gets mono during their teenage years

This list could go on and on forever, but you might get pretty bored: I’ve learned a lot. I’ve really enjoyed this summer: my lab was wonderful, the people fun, and the program stimulating. There’s not really anymore to say except: I’m glad I did it.

Until the next time I blog,

Lisa
 

With a jolt, I note that the tissue culture room clock reads 3:45 sharp. After popping the cells I just split into the incubator, hurriedly cleaning the hood with ethanol, and shutting down my computer, I dash off to the latest seminar in the French Family Science Center.

Contradicting my initial uneasiness about the seminars, these talks from the most prominent scientists around Duke have been incredibly beneficial. Each speaker opens a window into a new world of science and information. Did you know that the platypus secrets milk through chest and stomach pores, like sweat? Or that variation in influenza virus surface proteins hemagglutinin and neuraminidase inform the names H1N1, H5N1, and H3N2? Beyond the fascinating factual tidbits, I’ve realized how extensive and cutting-edge Duke’s research really is. It’s stunning to watch each presenter unfold scientific secrets, whether about cell cycle regulation or cell invasion. Furthermore, every speaker’s background demonstrates that years of extremely hard work created each brief presentation and moved these researchers to the top of their fields.

But most importantly, the seminars emphasize how incredibly lucky I am to be researching at the same university as these scientists. Their constant drive to discover the world around them amazes me and inspires me to work hard at my own lab. With so much exciting research going on, Duke is a great place to be.

So, as I temporarily pause my lab work to hear each new speaker, rather than feeling annoyed at the interruption, I’m excited. I wouldn’t miss it for the world.
 

So what exactly am I doing here? Oh that’s right, research. In the spirit of expanding the vast body of scientific knowledge, I will now tell you my exact research question, and then spend the next five weeks performing experiments to determine that question’s answer. After enjoying a few weeks in the lab learning, I’m now embarking on the wonderful journey towards the research conclusion.

You’ll have to learn a little bit more about epstein-barr virus before I explain the research question…

Epstein-barr virus, or EBV, infects over 95% of human adults. Most people acquire EBV around age three, when it causes a mild immune response. However, in today’s germophobic society, some people do not contract EBV until their teenage years, when it provokes a much stronger immune response. This EBV-induced teenage sickness is known as infectious mononucleosis, more commonly called mono.

The first time a person contracts EBV, whether as a three year older or a teenager, is termed the primary infection. During primary infection, EBV infects both epithelial cells and B-cells (B-cells, or B-lymphocytes, are an integral part of the human immune system). Even after the primary infection, EBV remains within some B-cells for the rest of the person’s life. This isn’t to say that we remain sick all the time; that would be a most unfortunate situation. The virus, instead of actively infecting new epithelial cells and B-cells and making you feel sick, remains “hidden” within certain memory B-cells. As the virus is not actively propagating, infecting new cells, and causing sickness, the virus is said to be in the latent stage. Latency is completely different from the lytic stage, when the virus is actively reproducing and infecting epithelial cells, such as during mono.

Occasionally, the virus tries to use the long-lived (or immortalized) memory B-cell that it hides in to re-establish an active infection, causing the infected B-cell to replicate and proliferate. Hmmmm, long-lived, proliferating B-cells? Doesn’t that sound like cancer? In fact, that’s exactly what it is. Fortunately, most people’s immune systems do a pretty good job of beating back these sporadic EBV uprisings, and EBV remains blissfully latent for the rest of their lives.

But what about those people who have compromised immune systems, who are immunosuppressed? The EBV-infected, immortalized B-cells can then proliferate freely, causing a whole host of B-cell lymphomas. Such cancers mostly occur in persons who are on immunosuppressant drugs for organ transplants, have AIDS or malaria, or are malnourished. Since EBV causes lymphomas during immunosuppression, EBV is called a co-factor for these cancers. Burkitt’s Lymphoma, the most common childhood malignancy in sub-Saharan Africa, has an EBV co-factor. Nasopharyngeal carcinoma, another cancer with an EBV co-factor, is frequent cancer in China and Eastern Asia. Here in America, Hodgkin’s Lymphoma is the most well-known cancer associated with EBV.

For my work, I am looking at whether certain subpopulations, or types, of B-cells are more sensitive to infection and immortalization with EBV than others. I am particularly interested in a B-cell marker known as CD226. In an experiment, our lab noted that only about 3% of normal, uninfected B-cells have CD226. However, almost 100% of EBV-infected, immortalized B-cells in vitro (known as lymphoblastoid cell lines or LCLs) are CD226 positive. In a preliminary experiment run over the last couple of weeks, I’ve found that CD226 becomes increasingly expressed over time in populations recently infected with EBV.

So the now the research question is, “is CD226 upregulated by EBV, or are cells that are CD226+ in the first place more sensitive to EBV, and grow out into LCLs?” In this case, upregulated simply means that EBV causes B-cells to express more CD226 by causing the CD226 gene to be expressed more. I’ve come up with 2 hypotheses that represent what could happen in each case…

Hypothesis 1: EBV Upregulates CD226 Expression

If B-lymphocytes are sorted into CD226+ and CD226- populations and then infected, both populations will increasingly express CD226 during outgrowth into LCLs, especially the CD226- population

Hypothesis 2: B-cells that display CD226 develop into LCLs when exposed to EBV

If B-lymphocytes are sorted into CD226+ and CD226- populations and then infected, the 226+ population will develop into CD226 expressing LCLs, while the 226- population will die off and not experience outgrowth into LCLs.

Of course, the increased CD226 expression in LCL could also be a combination of both upregulation and preferential development of CD226+ cells into LCLs! That’s where this gets complicated. Stay tuned over the next few weeks (and perhaps into the fall) to find out the results.

Some notes of correctness: The term “immortalized” to refer to latently-infected B-cells is somewhat disputed, as these cells do have extremely extended life spans but do not actually proliferate indefinitely. Also, I hope you will excuse my occasional personification of the virus, which I assure you I only employed in the interest of simplicity :)

Responsible Conduct of Research? Like, ethics? You mean I have to go to a seminar on that? Man, couldn’t we talk about something more interesting, like, I don’t know, cell cultures?

Responsible Conduct of Research is one of those topics that science researchers study in some graduate class, groan about how boring it is, then forget about before continuing on with their lives. Yet taught correctly, RCR is supremely interesting, highly relevant to research today, and (I’ve now realized) incredibly important to learn about. Last Wednesday, Alex’s superbly engaging seminar genuinely sparked my interest in RCR and the politics surrounding science research. During the seminar, we watched the movie “And the Band Played On” with director Robert Spottiswoode (kudos to Alex cause this movie is fantastic! If you haven’t seen it, I HIGHLY recommend it. Seriously. Go rent it RIGHT NOW).

“And the Band Played On” is an adaptation of Randy Shilt’s non-fiction book about the HIV/AIDS epidemic. The movie documents HIV’s rise from discovery to epidemic, especially focusing on the politics behind the government inaction about HIV and the HIV discovery. Of notable importance is…
1. The American government and research’s amazingly slow response to do anything about AIDS, because AIDS was perceived as a “homosexual disease”
2. The unbelievable saga between American scientist Robert Gallo and French scientist Luc Montagnier about who should have credit for the discovery of HIV.

During the movie, I felt hatred for the scientist Robert Gallo and frustration with the politics surrounding AIDS. People were dying from HIV; why did Gallo insist on squabbling with the French for credit over the blood test patent, delaying its production? HIV was spreading throughout the gay population, yet Ronald Reagan still hadn’t said the word HIV in a speech; why wouldn’t he acknowledge the epidemic and give AIDS research funding? HIV was potentially in the blood supply, so why did the blood board turn a blind eye and bleat about needing scientific proof?

Things are better today, right?

Yeah, maybe we think so. Neither I, nor my colleagues, would ever steal research from one another; that would be unethical in the extreme. But the challenges of RCR aren’t simply black and white.

RCR isn’t just about making sure you don’t falsify and steal data. What about if you know that someone else in your lab falsified data? Do you turn them in, accusing your colleague of misconduct? What if the errant person is your superior and you will lose your research job if you turn them over?

What if it seems that someone in your lab falsified the data, but you are unable to solidly prove it? Should you talk to someone about it? Could talking to someone about it destroy your lab’s credibility?

These are hard questions, and when you’re right in the middle of research politics, sometimes it’s harder than one might think to perform up to ethical standards. For most researchers, falsifying data is incredibly unethical, and we would never fabricate results. So the real challenge comes when deciding what to do when others falsify data. Pressure to publish, pressure to work well with your colleagues, pressure to keep your job, and pressure to build a name for your university all push against reporting misconduct. But certainly, science must focus on much more than awards and names, for ideally, humans study science to create accurate, useful empirical knowledge about our world. Perhaps sometimes researchers forget this overarching goal in the glory of a perfect paper, but when science becomes most about the awards than the knowledge, it’s missing a little something. Ensuring the ethical research conduct of our colleagues should be at the forefront of our research ideals. And just as RCR problems are not black and white, neither are the solutions; there are many ways to ensure the ethical conduct.

Alright, time for me to come away from the altar. Now go watch that movie.

Interesting note about the movie title: “And the Band Played On” apparently references the band/orchestra on the Titanic, which supposedly kept playing even as the ship sank to the depths of the ocean. Rather an adept analogy for the politics surrounding the early 1980’s AIDS epidemic  Also keep in mind that the movie characters and the dramatization are probably exaggerated and oversimplified. Still, the film is certainly engaging and raises intense questions about RCR.