Debbie Knight

Archive for the ‘observation’ Category

Lost bits of research history: Smallpox

In observation, research issue(s) on July 8, 2014 at 5:41 pm

virus

Two news articles I read today told of several vials of Smallpox dating back to the 1950’s that were discovered in an unused National Institutes of Health storage room — in an unauthorized lab space.

A little scary, yes.

But you might wonder how could that happen?

In the past couple of years, I’ve personally cleaned out several laboratories of researchers who have moved on or retired. I can tell you that a box of vials could easily find its way to the back of a cabinet or deep in the permafrost of an ultra-low freezer.

Now when I cleaned out these labs, I didn’t find anything so dangerous as vials of freeze-dried highly restricted human pathogens. Thankfully!

But what I did find was a combination of disgust and amazement. Rusted cans of disinfectant, plastic containers of formalin-fixed mouse bits, microscope specimens that might have dated back to the turn of the century, chemical bottles with peeling labels and rusted lids.

Many years ago, when my department allowed researchers to scavenge equipment (perhaps a better term would be “upcycle”?) from a retired researcher’s lab, I found a long-dead octopus named Cornelius floating in a jar of murky formalin. He was circa 1980’s — not quite the 1950’s like the specimens found in the NIH lab.

Had these things not been removed from the defunct labs, these lost bits of research history might have passed unwittingly to the next researcher to take possession of the lab space.

A prime example of this can be found in a news story from three years ago. A researcher discovered a dusty old box containing experimental samples dating back to the 1950’s of his mentor who previously occupied the lab space. And the researcher found a wonderful new finding waiting to be discovered.

So, the discovery of long-forgotten vials of Smallpox in an unauthorized lab IS big news. If not, disturbing news.

But how those vials from the 1950’s wound up in a rarely used cold storage room may not be as sinister as it might sound.

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D’oh! Moment #429

In observation on March 14, 2013 at 11:32 am

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This illustration I found on PhD Jokes’ Facebook page made me laugh because it’s so true!

I can’t tell you how many times this has happened to me. You have your 8-channel (or even a 12-channel) pipet aid, tips loaded and (blam!) one of the tips falls off.

You can carefully tighten down each of the eight tips before dipping them into the solution you are transferring, yet somehow it happens.

You suspect that tiny gremlins are at play because you did, after all, take the time to make sure each tip was secured. There could be “no” other explanation like you bumped the tip on the side of the plate that helped dislodge it. Nope, certainly human error is never a possibility. It must be, without a doubt, gremlins.

Okay, so it’s highly unlikely that the oft blamed creatures are the source of the problem. And even more unlikely that your lab mates or your boss would believe such a tale.

So how to fix such a predicament.

Well, sometimes you get lucky. The tip lands in such a way (like back in the appropriate well or somehow upright) that you can carefully pick it up and “save” the experiment by reattaching the tip.

And … sometimes you can’t.

Sometimes you will have to add a new tip – carefully – without touching any of the others still in place on the pipet aid.

Sometimes you just have to transfer the samples you have and come back, armed with a single pipet tip, and load the lost sample separately.

But there are times, like when you are transferring everything from one well to another  that  by dropping the tip, you’ve managed to lose the entire sample. There’s no coming back from that. Unless … in your infinite wisdom you built in replicate wells into your experiment (i.e., you designed your experiment to have multiple wells testing the same experimental condition).  This is always a wise thing to do.

Another problem that can arise from dropping a tip: when you are transferring infectious or radioactive samples. This is certainly worthy of an expletive or two. You’ve just created a bigger problem. Not only have you possibly lost an experimental condition, but now you will have to decontaminate the working area before you can continue.

Sure, I can laugh at the joke in the illustration above. Now.   While sitting at my computer typing this post. However, it’s not quite so funny when it actually happens during an experiment. And, yes,  I’ve been known to say an expletive or two, sometimes they’re rated G and sometimes not so rated G.

Of course, my most caustic string of expletives will never be a match for one of my lab mates from days long past.

Noelle was the best  at stringing along expletives when experiments go awry.

She sounded a little like the Looney Tunes character, Yosemite Sam.

yosemite

You could hear her mutter the curses under her breath and it really did sound a lot like “sassafrassin’ raggafrackin’ fillaburgin’ braginstachin’” except they weren’t nearly so tame.

Her rants always made me chuckle.

Quietly.

So as not to further disturb her.

Ah, the good ol’ days.

Hanging up the lab coat

In observation on February 28, 2013 at 9:30 am

lonely lab coat 1Today,  my lab neighbor and office mate officially hangs up his lab coat for the last time as he retires from the university.

What this means is he has put in an equivalent of 30 years of service, so he can begin drawing retirement benefits from the public employee’s retirement fund.

But what it doesn’t mean is that he will completely retire from the workforce. It’s highly likely he will find another job elsewhere (and by “elsewhere,” I mean “not in the research lab”).

He will reinvent himself. Try something new. And I wish him well.

But I must admit I’m a little jealous especially since I have a considerable ways to go before I could do the same.

But more importantly, he’s getting out of research just as things are about to get tougher. Way tougher.

As sequestration looms large over the nation, its impact may mean a 5.1 percent cut in National Institutes of Health (NIH)  funding ($1.5 billion of the total).

And according to an announcement made by the NIH, it will likely “reduce the final (fiscal year) 2013 funding levels of non-competing continuation grants and expects to make fewer competing awards to  allow the agency to meet the available budget allocation.” [Translation: funding of existing grants may be reduced and fewer new grants will be awarded]

So, it will be even harder to get grant funding than it already is (and believe me, it’s already tough!).

But it also means that even grants already awarded may suffer reductions in the actual paylines.

I know one researcher who was only given half of this year’s award — the other half held back in case the governmental budget cuts were as severe as predicted. Now, she may not get the other half. This means she won’t be able to do much of the research she proposed to do in the grant that was funded. This means that she may have to let one of her employees go. This may negatively impact her chances of future funding. And I won’t even mention the advances in skin cancer research she might have made.

Of course that could be said of all the possible scientific advances which could be slowed significantly by these budgetary cuts.

It’s a bad time to be in research and to be dependent on government funding for your livelihood. And it sounds like we will have to tighten an already severely restrained belt.

So, Pete, your timing is impeccable! I wish you well in your future endeavors. And don’t forget about those of us still in the research trenches, frantically panning for that research “gold!” 🙂

A story behind the research

In observation on February 6, 2013 at 9:00 am

One of the great things about going to a talk given by a scientist is that they sometimes drop in a little anecdote about their research.

I attended such a seminar yesterday.

The visiting scientist gave a talk about breast cancer. While this isn’t my area of research interest, I went primarily because it was my department’s seminar series and I felt obligated to attend.

It turned out to be an interesting talk about the effects of mutations in a receptor protein, its ligand and their influence on cancer cells.

But even more interesting was when she told us one of her technicians had manipulated some cultured cells so they no longer expressed the ligand protein (The protein is called Ephrin A1, in case you’re wondering.)

The technician noticed the treated cells had quite a number of little bubbles (or vacuoles) in them, more so than the untreated cells.

He mentioned this to his boss, the woman giving the lecture.

She admitted to the audience she dismissed his observation as an artifact from the treatment method (that would be transfection for those wondering).

But the technician thought there was something important going on. So without asking, he stained the cells with a special dye called oil red O. This dye stains fats (or as we call them, lipids).

Those little bubbles in the cells were loaded with fat.

His finding led to a whole new area of research in her lab.

She said she was happy that her tech hadn’t listened to her. (Take note all you research students and research associates out there!)

You’d never get that little nugget of fun in a scientific journal article.  But maybe scientists should include them 🙂

That’s the report I’m filing: the scientific manuscript

In observation on January 16, 2013 at 9:30 am

Submit

A friend of mine, a fourth-year graduate student, just submitted a manuscript to the scientific journal PLOS One.

Her name is listed as the first author on this, her first manuscript submission.

It’s a pretty big deal to write that first first-author manuscript. It’s your research, it’s your baby.

Naturally, she’s very excited about it.

It reminded me of my first first-author manuscript, written so many years ago. I remember it was quite a task to write the beast. It consumed a large part of my life while I gathered and graphed data, plunged into the existing scientific literature.

The writing did not come easily for me.

Every word was written knowing full well that it would be heavily scrutinized by my boss, the reviewers and other scientists.

By the time the manuscript was submitted to a scientific journal for review, my boss had so heavily edited what I wrote I barely recognized it as “mine.” I was really surprised my name was still first.

It was a humbling experience.

But it was a huge learning opportunity.

My next manuscript was a little easier to write.  And a little more of my writing remained untouched.

When that first manuscript was accepted and published in a scientific journal, I sent copies to everyone I knew. It was so cool to see my name in print, to have my research efforts out there in the scientific community.

It’ll be interesting to see how my friend handles it if and when her manuscript is finally published.

Of course the manuscript will have to run the gauntlet of editors and scientific reviewers.

Best case scenario is the manuscript is accepted for publication with no changes required.

But more likely, the reviewers will have some issues that she will have to address either in writing or through more experiments. In this case, she would need to make the necessary changes and resubmit the manuscript for further scrutiny.

Then there’s the worst case scenario. The journal’s editors will reject the manuscript because the work is not appropriate for their journal. In this case, she would have to take stock and retool the manuscript to submit to another perhaps more appropriate scientific journal.

I have my fingers crossed for the best case scenario!

————————————-

So what does a scientific manuscript look like?

It is pretty much a technical report. It has a very defined structure, a formula if you will.

First is the introduction which puts the research in context – historically as well as biologically. The last paragraph of the introduction should include what your data shows.

This isn’t storytelling where you hold the punch line until the end. Everything is revealed up front.

I find the introduction one of the hardest things to write.

Quite a bit of digging through the scientific literature happens before the first word is written. And including the appropriate depth of literature review is tricky.

The next section in most scientific manuscripts is the material and methods section.

This is where I usually start the manuscript writing process.

I advise any first-timer to start here!

Why? It is by far the easiest part of the manuscript to write. It involves writing about what reagents you used and how you performed the experiments.

If you kept a very meticulous lab notebook, all this information is at your fingertips. Reagent specifics such as catalog numbers, supplier names and company addresses as well as antibody clone designations, antibody isotypes and associated molecular tags are often needed in this section. Sometimes that means you have to hunt for the data sheets that came with the reagent or dig through a stack of packing slips to find the specific details you need for this section.

You learn quickly to include this information in your lab notebook after you’ve worked on your first manuscript.

The next section is the results section. This is the next easiest section to write — although it’s not nearly as easy or straightforward as the materials and methods section.

This is where you tell your research “story.”

Here you present the data as graphs, tables, figures, photos, etc.. Each figure needs a description, a figure legend, that should be able to stand alone. Sometimes this is the only thing a reader will read in the article.

Generally, the first line of the figure legend summarizes what the figure is showing – kind of a title or a headline.

It is then followed by a brief description of the method used as well as what the figure shows.

If written well, the reader shouldn’t need to even look at the accompanying image.

What’s tricky with the results section is figuring out what data presented in what order will help you tell your story best.

Many researchers tell the story how it unfolded, often starting with the original observation that sent them on their journey.

The researcher will then show how they proved what they thought was happening was actually happening.

Sometimes that story takes a twist – an unexpected outcome of their investigation. I find these most interesting to read, to see how researchers roll with the punches.

Sometimes the story unfolds in a straightforward and logical manner.

Sometimes the researcher offers their interpretation of the data in this section, but more often the significance of their discovery is discussed in the last section, the hardest section to write, the conclusions (or sometimes discussion) section. In this section, the researcher places his data in context with other scientific data. This may require a lengthy explanation why his data flies in the face of other scientist’s data.

Some researchers expound on the subtleties of their findings.

Some researchers will wax philosophical. Some will stand on their soapbox.

There is quite a bit of style variation in the conclusions section.

And, yes, there is a bit of overlap in these various sections.

You need the overlap because different readers start at different places within the research article. Some readers will only look at the conclusions. Some are only interested in a particular method or a particular part of the puzzle.

I know that I can read the same paper at different points in my research project and get very different information out of that paper. At the start of the research project I might only be interested in a particular method. At another stage of the project, I might want to see what their data looked like or how they interpreted their findings.

So there you have it. Scientists do their research, perform the experiments to better understand a phenomenon, and report their findings to the scientific community. (At least that’s how it happens in the university setting.)

The hardest exam a Ph.D. will ever take

In observation on December 3, 2012 at 11:10 am

candidacy exam

You would think that the hardest exam a Ph.D. graduate student in biological sciences would ever take would be to the dissertation defense.

But it’s not.

It’s the candidacy exam (aka the general exam).

This exam probes the depth of the student’s knowledge, pushes the boundaries of that knowledge, and forces the student to create something new out of that knowledge. Something that she has never thought of before. Right there, on the spot, in front of a group of highly intelligent professors.

Today, the graduate student in my lab is taking this exam.

She’s nervous. Understandably so.

Did she study enough? Will she remember it all? Did she study the right stuff?

Lots of second guessing.

She knows that if you took all the final exams  from every biology class she has ever taken, pool it into one huge mother-of-all-exams, that she might approach how challenging this exam is.

The candidacy exam at my university consists of a written as well as an oral portion.

There are a few variations on this exam. At least the written portion.

There’s the “traditional” format where each day you get a set of written questions from one of your committee members. You have the entire day to answer those essay questions. Your brain is the only resource you are allowed, so you can imagine how much information you need to have at your proverbial finger tips. And after you’ve finished for the day, you have another set of questions from another committee members to anticipate. This portion of the exam continues until you have answered questions from every committee member, typically four or five members.

Another style of the written exam is “grant proposal” format. Here the student writes an National Institutes of Health (NIH)-style grant proposal.  Depending on what the student’s committee decides, you could write a grant proposal:

  • that has absolutely nothing to do with the research you are currently doing. This exercise gives the student practical experience in how to write a grant proposal — something that you will need to do in your research career whether you are in an academic, industrial, or governmental position. The drawback here is that you spends a great deal of time reading tons of journal articles on a topic that probably will not help them with your actual research project.
  • that focuses on your research topic but is unrelated to what you are doing in the lab. This style is a little more practical because you are reading journal articles that related in some way to what you are already learning in the lab. This exposes you to things beyond your research project, perhaps helps you see the bigger picture.
  • that focuses directly on your research but goes beyond what you are doing in the lab — perhaps these are future directions for your research. This is the most practical of the written exam formats. Not only are you writing a grant proposal that you could actually submit to the NIH, you are thinking about where your research project is going.

I think this is an “easier” format. It tends to focus the questions during the oral portion of the exam a little. It certainly serves as a jumping off point for the question-answer session.

Her committee chose the latter format.

She wrote her proposal weeks ago. And she has been studying furiously for the oral portion. Scientific journal articles stand in neat stacks on her desk.

Today she will be tested. Today is the oral portion of her exam.

This part is a little like hazing.

And it will go something like this. (This is a composite of what really happens on both sides of the door)

You, the student, will enter the room. Your fear is palpable.

The committee members will ask difficult questions, pushing until you are nearly in tears.

Two or so hours later, you will then be sent you out of the room while they discuss your performance and whether they think you have what it takes to finish your Ph.D. research.

This can take as little as five minutes to decide.

The committee will then sit around and shooting the sh*t for 10 or 15 minutes while you pace the hallway, sweating. On the verge of tears. Dreading the committee’s decision. Second-guessing your answers.

Your labmates will pass by and ask how you thought you did.

You’ll lie.

You’ll say that you did okay. But that’s not what you’re thinking.

What you’re thinking is that you failed miserably because you had to admit several times you just didn’t know the answer.

Those minutes standing in the hall will feel like hours. Maybe even days.

Will they ever come to a decision?

You will hear laughter.

Oh, oh. That’s not good. Is it?

More waiting.

You think about alternative career paths.

You think about moving back home with your parents.

You think about a lot as the minute hand sweeps across the hallway clock face.

Finally, the conference room door pops open.

A hand will wave an invitation to come in.

Unceremoniously, they’ll tell you that you passed.

It’s over.

Huge relief.

And then …

It’ll be a bit of let down because all those months of dread and worry, all those hours of stress, comes down to a simple “you passed.”

While it seems like an end, it’s really just a beginning of a new chapter. No more classes, just research experiments.

You’ll have your share of “woo-hoos!” as well as “what the heck?s”

You’ll look back on your research days with some fondness.

By the time you finish your research project, you will be the expert.

You will know your data inside and out because you lived it. Defending your dissertation, while it sounds daunting, is relatively easy. At least compared to your candidacy exam.

A reminder (to me) why I blog

In observation on November 9, 2012 at 10:00 am

Wow.  As a blogger, I often wonder if what I write is reaching anyone.

I’m sure this is something with which many bloggers struggle.

Today I got a comment on a blog post from July. “A reminder (to me) why I do research” was about a heart-rending email my boss received from a patient.

The comment, which I will place here anonymously, was equally heart-rending.

Here was another woman with a clearly debilitating medical condition, searching for answers to her medical mystery. And she stumbled onto my blog, presumably through an Internet search.

One line from her message gave my heart an extra twist: “I have no health insurance but the ER.” (Wow, that’s something I take for granted in my own life.)

Another gave me hope because she has people who really care for her:  “I have family willing to take me anywhere or do anything to help me.”

She wrote:
 “I am convinced I have Susac’s Syndrome. I have cotton wool spots, terrible chronic headaches, personality disturbances, hearing loss, confusion, memory loss and vision loss. My MRI is normal. … I have no health insurance but the ER.

“I read what you just wrote here and I was wondering, can you tell me what kind of specialist I should be sending my pleas for help? I have family willing to take me anywhere or do anything to help me. I just don’t know where to start.”

In an email sent to her privately, I will give her a name of a clinician with whom we collaborate. I hope he can give her sound medical advice and an idea where to start unraveling her mysterious illness.

Good luck, SZ! I hope your journey of discovery will lead to your restored health!

Whatever you do, be passionate!

In observation on October 19, 2012 at 12:20 pm

Overheard while standing in line for lunch:
“They gave me $40, but I would’ve taken $5. All I care about is linguistics.”

I’m not sure if the guy standing in line ahead of me was a tutor, a consultant or a young enthusiastic professor, but he said the above statement with passion.

Now, as a biologist, I’ll admit I don’t know much about linguistics. But I do understand about being passionate about what you do and not really caring how much you get paid to do it — you know, as long as the bills get paid (you have to be practical, after all).

In fact, that passion has kept me in an academic research lab for over 20 years — often times, for little pay. And, yes, there were times early in my career when I had to moonlight to make ends meet. But I’m not complaining. I find research engaging. And, on most days, I find its challenges rewarding.

I admire this young man’s enthusiasm. I hope it drives him and serves him well throughout his career.

Poster presentation? No sweat if you keep it short!

In observation on October 10, 2012 at 2:42 pm

I stumbled across a blog post addressed to people who present posters at a scientific meeting. Specifically, if the presenter is asked to give a 5-minute summary of their poster, it shouldn’t take 20 minutes.

This made me think of all the posters I’ve presented at scientific meetings. I was often asked for a brief overview of my poster by a person who stopped by. Was I able to give that overview in 5-minutes or less? The answer: it all depends if I practiced my spiel or not.

I’m not a “natural” at public speaking — even if it’s to an audience of one or two. So I need practice. Lots and lots of practice.

I practice alone in a room — a lot! And, yes, to the casual observer it looks like I’m having an animated conversation with myself.  A good reason to find a room with a door that locks.

I practice in front of my lab mates.

And I practice at least once in front of my boss.

The practice really helped fine-tune the presentation. I know exactly what I’m going to say, rather than stumbling around trying to find the point. Not knowing what to say can add minutes to a brief presentation.

I don’t use a script.  I want my presentation to sound conversational and organic.  I use the figures on the poster as my prompts. If I need an additional diagram to help me explain things, I add it. I find this a better solution than interpretive dance, smoke signals or wild hand gestures.

And, sure, I  talk myself into a corner sometimes. But I  also figure how to get back to the point. This makes for good mental gymnastics before the actual presentation.

The practice hones and polishes the presentation to a professional sheen. By the time I finish, my spiel actually sounds smooth, confident and authoritative — all the things I’m typically not in this situation.

I know. This seems like a lot of work for a 5-minute presentation. It is. And the more times you give presentations, the easier it gets.

Just remember, your poster is one in a sea of posters. You (and your poster) need to really shine to draw the crowds. So keep it short, keep it sweet. If they want to know more, don’t worry … they’ll ask.

New faculty member perhaps a bit short-sighted?

In observation on October 2, 2012 at 2:40 pm

Overheard in the hallway between a new faculty member and a student:
“I don’t like to work with volunteers in my lab.”

Wow. I’m sure glad that Dr. K didn’t feel that way when I asked him if he could use a student volunteer in his lab.

I was just starting my junior year at PurdueUniversity, majoring in biology. I would tell my friends that I wanted to “do research” but I had little idea what that meant.

One of my friends strongly encouraged me to find a lab in which to work. And by “strongly encouraged,” I mean shoved.

Looking back, I thank Chris for his tough love because it got me my start in a research career. But at the time, my timid undergraduate self did not appreciate it so much.

I remember meeting with Dr. K in his office, quivering in my Reeboks. One of his office doors opened to the lab and I couldn’t help but gawk.

This was the first time I had ever seen a functioning research lab.  Everything was new and wondrous. From jumble of pipes and nozzles jutting from the polished black soapstone benches to the array of strange glassware that lined the shelves, I was instantly awed by the thought that “science” happened here.

I’m glad that he was  open to a student volunteer. An extra set of hands in a lab with limited funding.  While it would cost him (and his graduate student) the time to train me, it turned out to be a good investment. I came to realize that I loved working in a research lab and he got free labor.

When summer came, he hired me as a part-time student research assistant. I continued to work in his lab even after I graduated with a bachelor degree. He then hired me as a full-time technician.

So, I think this new faculty member might be a bit shortsighted by not allowing volunteers to work in his lab.

You never know where it might lead.