Mistakes, misconduct and modeling (three entirely different things)

As Nicole commented, increasing the odds of success goes hand in hand with increasing the failure rate, but I worry a great deal about making mistakes. I fear that despite taking care to check and recheck my work, I’ll overlook some fundamental flaw. Part of this fear is based on my assumption that most retractions are due to human error, with scientists making honest mistakes, but this PNAS article argues that most retractions are in fact due to misconduct. I expected that most of the misconduct would be due to instances of plagiarism or duplicate publishing that, while unethical, do not undermine the work of future scientists. I was wrong about that too–most of the misconduct was actually fraud. On the bright side, this article suggests that I can drastically reduce my odds of having to make a future retraction by doing what I’ve already been doing–being honest about my results and how I obtained them.

But I find this article especially disappointing because the scientists at fault came so close to making a contribution and then did the opposite. I am currently in the process of synthesizing noisy data from a model to refine an experimental design, and creating data has not turned out to be a trivial exercise. My motivating question is, assuming malaria parasites multiply in a petri dish just so, will our experimental design allow us to draw the correct conclusion?

Malaria in culture: what are the parasites doing in there and how will we know?

It requires clarifying my assumptions about the way the world works and about inherent observational error. Some of my favorite papers use models to test experimental methods rather than the other way around–like Fenton et al., who use a model to show very nicely that if there are interactions between coinfecting parasites, the signature won’t necessarily show up in prevalence data. The scientists who falsified data must have had a clear set of assumptions about the way the data ought to look (i.e., a model), and if those scientists had used the data they generated to inform their experimental protocols instead of reporting it as true observation, the resulting paper would have improved the quality of future science instead of diminishing it.

A Rough Rider

Time for a little American history lesson. Appropriate indeed as we have a great number of bashing (appropriate British adjective for awesome?) brits, a head kiwi, a couple of Robert Burns loving Scots, a quirky Canadian and a couple of recently departed team members of the “Oranje”.

Check this guy out.

I’ve wanted to write about Theodore Roosevelt for a while now, but was hesitant thinking I wouldn’t be able to appropriately convey how awesome he was. Too much time has elapsed, however, so I’ll just throw caution to the wind and I’ll do my best to impart a slight flavor of this giant persona and hit on a few themes that may be particularly intriguing for young scientists. For a more extensive history and an absolutely brilliant account of his life, see The Rise of Theodore Roosevelt, by Edmund Morris, the first of a series of three books to chronicle his life, which is currently on loan to Katey, with the possibility of a future transfer to Laura.

Some of you in the group have probably heard me babbling from time to time about Theodore Roosevelt, quite possibly the most interesting and admirable of the United States Presidents. Widely quoted by politicians, respected by conservationists and third from the left in this picture:

I first became enamored with Theodore Roosevelt not after hearing about him in early history classes, or even after reading Edmund Morris’ biography, but rather after stumbling upon an original work of his entitled Through the Brazilian Wilderness, which is his first hand account of an expedition he undertook following the conclusion of his presidency, along with some biologists of the American Museum of Natural History of New York and the Brazilian government, to collect specimens and map previously uncharted geographical features in an area of the Amazon.

I had an idea of Theodore’s affinity for nature, mostly from the simple fact that he was a dominant force in the establishment of the country’s first national parks, but I was staggered upon reading his accounts of the biodiversity he encountered in the Brazilian jungle. His attention to detail and the enthusiasm behind his introductory descriptions of the poisonous snakes handled by Doctor Vital Brazil left me incredulous that these were the thoughts and observations of a politician and not a scientist.

As a result of this work, I developed a deeper understanding of Roosevelt as a naturalist and an explorer. His blaring personality and virility leave the reader rolling their eyes at times, but my overall impression was highly favorable. Nestled within the abrasive masculinity (which I actually found quite endearing), and the over-done patriotism, was the footprint of an agile thinker, an ecologist and an adventurer: qualities that I never got exposed to during history classes that featured his mention.

In Edmund Morris’ first book I read about his early sickly years as a young child with asthma and his subsequent dedication to exercise that eventually cured him of his malady, his early interest in nature, especially birds, a change in his trajectory that converted him from pure naturalist to politician, a complete obsession with reading (nearly a book a night), and an ability to write books and articles on a variety of subjects in the form of historical analyses, biographies, naturalist observations, political statements and first hand accounts.

This got me wondering? How does a single person keep such a variety of interests? I recall Andrew saying that the average tasks/concepts one can keep track of at a time is limited at 5, but Roosevelt seems to far surpass this. The most impressive aspect is that he was seen as a colleague in many fields, not only showing interest in a variety of subjects, but also actively producing work in each field.

Now I’ll have to issue some self-restraint or I could fall victim to listing all the qualities and deeds of Roosevelt that left me in awe, and this might resemble a love letter or give the impression I’m forming a cult of personality around the man…

Apologies. Clearly my admiration for the man is high. But how can you not get wrapped up in a character who is a mosaic of swashbuckling pirate, quiet naturalist, dedicated athlete, and also happens to be a politician? A man who gained respect during his time as New York City’s Police Commissioner by enforcing a previously lax law forbidding the sale of alcohol on Sunday. Yes, people praised the man for forbidding the sale of alcohol. By forcing a complete enforcement of the law on all levels of society, he exposed the injustice of a law that was previously only limiting sale of alcohol to non-elite members of society. He in a sense showed the vestigial nature of a law by focusing attention of the entire body (in this case, residents of New York) on it.

So what can a young scientist like myself learn from such a man?

1.)  It’s absolutely possible to have multiple interests. Success will ultimately stem from this. Roosevelt was often approached by experts in diverse fields, even before his rise to presidency. He effectively acted as a keystone, or as a critical node if you will, in the formation of many policies, by providing a bridge among experts that had him as a commonality.

2.)  It’s not sufficient to have interests, but active participation in the field and contributions.

3.)  Read and write as often as physically possible.

4.)  You can’t be afraid to make enemies.

And most importantly and most indicative of how Roosevelt lived his life:

5.)  Success comes from action. Roosevelt wasn’t just a bundle of ideas, but rather showed a complete execution of his thoughts. I find this last statement something I should particularly pay attention to. Nothing ultimately comes from a head full of ideas or a wide-eyed interest in a variety of subjects. Active participation and production is ultimately important.

Oh yeah. And on a swim in Cuba, upon being surrounded by a group of sharks, his reaction, unlike those of frantically waving onlookers on shore or his terror-stricken swimming companion, was one of confidence and an assurance that they would not attack, backed up by multiple readings of his on shark behavior. Roosevelt the marine biologist.

Blokes, join us…

The group has become very female-biased.  This is what rare male advantage looks like.

Post-doc Dave Kennedy and his post-doc harem, Christmas party, 2012…

Of earrings and flowery shirts

A tad late (which only means I am already fully integrated into the Spanish culture) and with a real cup of coffee in front of me, I will try to write a professional blog on my time with A&M.

I vividly remember my very first encounter with Andrew: we had proper coffee in a coffee place somewhere near his department in Edinburgh. His whole lab, including Silvie, would soon move to the US of A, and I was the jobless spouse who would simply tag along. I guess he wanted to see who I was and what I did. Although it was freezing cold, I was sweating the whole time… He asked me (very good) questions about my dissertation, but I often had no clue what he was talking about. For some reason (probably because I knew what a mosquito was), he offered me a job. I would work for Matt, whom I never met before…

And there I was, January 2008. Alone in a dirty and moldy office in CEL, complete with grandpa furniture and yellowish insect images on the wall. And with Matt as my boss… 😉 These were the early days. We had no incubators and it was a year before the first experiment would take off. But hey, I didn’t care: Very soon we would have a brand-spanking new insectary, an Anopheles gambiae insectary and Plasmodium falciparum up and running!

I was given all the freedom to come up with a line of research (from Andrews’s blog below, I would pick the following verbs: encourage, stand back, stimulate and cheer). For months I pooped out one figure after the other in excel, to show the bosses I was onto something. The white board proved invaluable: Matt and I had many white board sessions, shaping current ideas, and exploring future research directions (I truly miss those sessions). And one day, more than a year after my arrival in State College, the psychedelic plot was born. The rest is history 😉

The past five years have been a fantastic roller coaster ride. Some years were clearly full of loops and corkscrews, during other years we were more on the chain hill. But hey, you have to gain height, before you can get your ultimate thrill!

I learned an awful lot from our silverbacks. I did not only benefit from their scientific intellect, but often sat back to observe their way of leadership. From how they pitch ideas to why they hire the people they hire. I think they taught me invaluable lessons without even knowing they were teaching me. Off course there are always things I would do different, but thanks to them I feel ready to continue on my own now. I just hope that I won’t crash into the first window I encounter…

♥ I miss you all guys!

Ninth time’s the charm

I recently decided, again, that I should learn to use R to graph and analyze my data. The decision was a form of, in Monica’s words, productive procrastination, as I was supposed to be putting together my presentation for lab meeting. But, wherever the motivation invaded from, the R infection finally took off and successfully established; I’m loving it! I’ve been thinking about why, this time, I decided to keep forcing through the confusion and why now (nerd alert!) I think it’s so much fun.

I first set out to learn R at the end of my first year of grad school. Overwhelmed by how very much I did not know about everything, my poor soul couldn’t take the blank stare of R’s option-less console, or its lightning rejections of my attempts to make it do what I wanted. (Or do anything except issue vague and vaguely disdainful error messages about how massively or minutely wrong I was.)

Now what?

Later, when I had more of my own data, committing the time to learning another way to look at the data seemed frivolous. After spending an afternoon making a list of odd numbers from 1 to 99 or the alphabet backwards, I would go back to SPSS, where clearly-labeled menus meant your p-value was just a few simple clicks away!

Anyway, I’m not entirely sure why I’ve moved past these hang-ups- I certainly don’t know much more about everything or have more time to spend getting to results- but I think it has to do with a new outlook. Now, I see using R like solving a series of puzzles with only a limited set of random tools. When what I thought I would see on the screen actually appears, it makes me feel MacGyver-y and oh-so-clever. Like I could survive living on a deserted island with only a jumprope and a pack of gum.

I’m sure the thrill will wear off…I’ve only JUST started trying to do statistical tests, and it’s going far less well than the graph-making…But, for now, if anyone needs me, I’ll be victory-dancing in my cubicle.

Of new beginnings

Two weeks ago it painfully sank in that I had completely missed out on a major transition in Silvie’s life. Leaving her nurturing scientific nest in the Read Lab to take a brave dive into a new world in yet another foreign country, beginning a new episode… Luckily I got to spend an hour with her on her last day on campus and was able to share some tears but also present to her the subject of my distraction form anyone else’s life.

While Silvie and Krijn had been finishing up projects, packing and shipping belongings overseas, having last dinners and toasts with their loved ones, I was preoccupied with preparations for a new beginning myself. I had taken off work before the due date of my second child and was spending my time at home exhibiting perfect nesting behavior.

The baby had been due beginning of the month, but the due date past, and the new earthling was showing no intent whatsoever to come great this world any time soon. I was joining my three year old bouncing up and down the stairs, I raked leaves, and hiked all the way up Mount Nittany, but none of it helped. There was no choice but to give in to the thought of eventually being induced. The doctors scheduled me for Monday November 12, a day after Marcel’s birthday. At least we were going to be having a birthday party for him then. But given the early appointment I had been given for the induction on Monday, we decided to have the birthday party on Saturday night instead of Sunday, so everyone would be able to drink lots of wine, sleep in, and cure eventual hangovers.

We spent Saturday preparing a birthday dinner: my god mother made a fancy first course with smoked trout, fennel and orange, I prepared the first lamb roast of my life, and Marcel’s postdoc’s wife brought a to-die-for home made German Schwarzwälder Torte. The evening promised to be a success. After we had been for a short walk in our neighborhood park – the usual picture of us, a family with a toddler and a black cat – I felt some muscles contract in my abdomen. Somewhat excited I told the others, but hey – these practice contractions can last for days.

We started eating and the contractions continued, but I kept telling everybody to relax. They were hovering over me but I just wanted everyone to have a good time, we were having a birthday party after all! And again, these kind of contractions were possibly going to last for hours if not days before becoming the real thing. I don’t know whether they believed me, something told me they didn’t. When my contractions became more frequent I was starting to write them down. ‘Relax’, I kept saying, ‘open another bottle of wine and enjoy! I am just fine…’.

We made it through all courses, everything had been just divine, and I was stuffed to the rim when the contractions became definitely more severe, and we decided that maybe I should call the hospital to ask for advice. I was told on the phone that I should probably come in to check for labor, and so the guests had their last glasses of wine and were slowly preparing to go home.

Marcel and I left the house at 10:47pm that night, and Elina came to great the world at 11:43pm. There were mere 17 minutes between the ‘time of admission’ and ‘time of birth’. She was very much in a hurry all of a sudden and, it seemed, determined to have her own birthday after all. And what a considerate little person to have let us all first taste that birthday cake!

From humble beginnings

R basics seminar given by CGSA Fall 2012, photo by Becky Heinig

A few weeks ago, a graduate student not associated with the Center for Infectious Disease Dynamics (CIDD) remarked that CIDD graduate student events have become a magnetic force within the community. This statement and its source have made me step back and take stock of the current position of the CIDD grad student association (CGSA). This semester marks a year and a half since we formed our organization and, looking back, I’m impressed by how far we have come in such a short time and by the level of energy among CIDD grad students.

Less than two years ago, the number of graduate students regularly attending journal club and other activities had dwindled to an average of 2-3 per week. Several of us were seriously concerned that the graduate community in CIDD would continue on the downward trajectory. This was not an acceptable outcome for me or for the other graduate students, because we recognized the invaluable experience gained by interacting with students outside our own lab group and discipline. The continued decline of graduate involvement in CIDD would have decreased those interactions drastically.

Creating CGSA was our answer to this problem, and I am overwhelmed by the result. This semester, not only has journal club been well attended, the discussions have been diverse and quite interesting. Several of our professional development seminars have been attended by students and postdocs that normally haven’t interacted with CIDD. But I think what has really driven home for me the fact that CGSA has now become entrenched for the foreseeable future is that this semester we have students asking for more opportunities to interact. I feel this points to a culture shift among the students; a few years ago, getting attendance at one event was difficult, now there is clamoring for more. The excitement and energy about research and discussing new angles with others is palpable. This shift, I think, has improved graduate education and experience and has given us a sense of belonging.  It has also allowed us to give back to the CIDD community by expanding CIDD’s reach through interactions with grad students and postdocs in other programs. I am interested to see the direction that CGSA takes in the coming years, and am proud to have been able to witness and to contribute to the inception of this organization.

The curious case of ice hats

A key indicator that someone is going to grow up to be a scientist, I think, is a propensity to look at the world and ask “What the…?!?”.

Having a live-in physicist has proven extremely useful for satisfying my (often fleeting) curiosity about lots of things, e.g., what is electricity? Why can’t something go faster than the speed of light? Or — stealing something from Katey’s curiosity — what would happen if there was no moon?

I was therefore surprised when my physicist couldn’t explain my recent curiosity, stemming from a bizarre finding in my freezer (Figure 1).

Figure 1. A picture of my actual ice cube tray and most recent batch of ice cubes. About 83% of the ice cubes in this batch were as expected (hat-less). The remainder had these astonishing little hats.

What the heck was this hat doing on my ice cube?!? I thought this wonder of science was sufficiently interesting to bring it up at lunch with my labmates. They offered a bunch of hypotheses for what could cause an ice hat. Maybe something was vibrating underneath the ice cube tray, or something was dripping from above it. Megan had the most inspired idea: could the formation of the ice hat have something to do with the purity of the water? The water in State College is notoriously hard, containing a lot of calcium. She thought that if I hadn’t filtered my water before freezing it, these impurities could provide a substrate around which the ice crystals could form. Turns out Megan was right, only in reverse.

Water with impurities does form ice around those impurities, but it also forms ice relatively slowly. Without impurities, water freezes so quickly that the water beneath the surface begins to freeze before the surface (which starts freezing first) is frozen solid. Since water expands as it freezes, the developing ice below pushes water up through the part of the surface that isn’t yet frozen. The surface of this emerging water freezes quickly too, so that as the water is pushed up and through a hole in the surface it freezes into a tube, which funnels more water upwards. This process generates what is known as an ice spike (though, I prefer the friendlier ‘ice hat’). The faster the water freezes, the taller the spike. With impurities, the water freezes slowly enough that the surface is frozen shut before a spike is made.

Apparently physicists could have answered my question, I just asked the wrong one. Two physicists published a paper in the Journal of Glaciology on this exact topic. Academia may be the only place where people get paid to satisfy their “what the…?!?” curiosities and that is pretty awesome.

Ice spikes are also pretty awesome. Make ice cubes from filtered water; impress your friends!

The end of the affair

To do science professionally requires a decade or so of training. Most of the training is a series of apprenticeships, where practicing scientists like me attempt to provide something which will empower the PhD students and post-docs to become more like, well, me. Quite what we provide is a total mystery. Relevant verbs: cajole, encourage, shape, unleash, stand back, teach, learn, watch, stimulate, underpin, raise, console, cheer, challenge, expand, argue, backup, disagree….

The process generates a type of personal relationship unlike any I have experienced elsewhere in my life. (Nicole calls me boss, and we both love the irony.) You spend significant chunks of your life – and especially theirs – together. You live with them through the highs and the lows, the cock-ups and the dead ends, the good ideas and the blowouts, the rejections and the eventual acceptances. Particularly when you are starting a research group, your future is totally, totally entangled in their future. And you struggle, almost daily, to provide the right balance of stretch and support (mmm, sounds like an underwear commercial). For me at least, it is hard not to get emotionally invested in the apprentices – it’s hard not to really care, especially as you watch them grow. Many early-career advisers struggle to get the personal/professional balance right.

But then the apprentices fledge. For a year or two, the relationship stutters along, usually as the last papers are wrapped up, or they come to you for career advice and endless reference letters. Then the whole thing more or less stops. You mostly hear from them only when they want something (usually another reference letter). You see them at meetings occasionally, when it is always good to have a beer and talk about the old times and find out how their lives are going. For those who have become advisers themselves, it is particularly good to hear how they are doing with their own apprentices. But for the most part, your ex-apprentices are gone from your life.

That is exactly how it was with me and my adviser. He opened the world for me, gave me extraordinary opportunities and insisted (screamed, shrieked, demanded) that I take them. Never once did he accept poor performance (“what do you call this?”). He gave me as much time with him as I could take. He surrounded me with the smartest people in evolutionary biology and leaders in the then nascent field of infectious disease ecology and he insisted I talk with them, work with them, learn from them. And by totally outrageous example, he taught me that you could live life to the full in this business. Then, after 7 years in his orbit, I just left, only getting in contact when I needed a reference letter.

I always felt bad about that. But somehow, now that I am more or less the age he was when I fledged, and after 30 or so of my own apprentices have flown the nest, it feels like that is the way it should be.

Bon voyage, Silvie and Kirjn.

Leaving the nest…

October 2004 – As a young 22 year old, I stepped into the office of Andrew in Edinburgh, Scotland. That was the start of a long and fantastic journey together. I was about to start a six-month Masters research project in his lab. Soon, my eyes were opened to the fantastic research environment of the University of Edinburgh, the quality and the enthusiasm of everybody in the lab, both PhD students and postdocs, and the stimulating research questions Andrew posed. After the 6 months were over, Andrew asked me to apply for a scholarship to do a PhD in his lab after I would finish my Masters. Two years later I would start my PhD.

November 2012 – Now 30 years old, I am once again in Andrews office, this time at Penn State and we say our goodbyes. With a lump in my throat I walk back to my office to clean up my desk. The past eight years have been really good and it is sad and frankly quite scary to leave it all behind. Much has changed, not only did I obtain my Masters and PhD, I also moved to Penn State and ‘obtained’ a husband and two children. Times change. It is time to leave my scientific dad and stand on my own feet.

Leaving Andrew is scary. How do you know you can do all this on your own? I guess time will tell. Andrew has been one of the best mentors one can wish for and has always worked hard to prepare us for this moment. He has always made me feel that he deeply cares, which I want to thank him for, a lot. The Read group and Thomas lab, past and present are a fantastic group of enthusiastic, smart and fun people. I will miss each and everyone of them, and especially my dear office mates Laura and Jessi; my tea water providers (and listening ears) Vicki and Nicole; Katey and her crazy and funny rants, all my lunch buddies and, most importantly, Megans baking. I’m sure we’ll see each other (including baked goods) again!

All, keep up the great work, can’t wait to see all the new papers coming out. Enjoy and benefit your time in this group, it will end before you know it.

Andrew, I will miss you! Thank you for all you’ve done.  Luckily leaving the nest doesn’t mean being out of touch.

Narwhals

A few weeks ago at the pub, Nicole mentioned that it can be hard gauge when a fellow postdoc (anonymous for this blog post) is being funny on purpose. “Yeah” I said, “I remember s/he said something about narwhals being mythical and I’m still not sure if s/he was joking or not.” And thus began the great narwhal debate of 2012.

As it turns out, Nicole didn’t learn about narwhals until college. An advanced age for what I consider to be basic knowledge, acquired prior to the limits of my memory. This revelation led to wild speculation as to the reason for disparities in narwhal knowledge. Based on the geography of our childhoods, Nicole hypothesized that distance to the ocean is associated with early knowledge of narwhals. Alternatively, I hypothesized that knowledge of narwhals is associated with an affinity for experimental biology, in contrast to modeling.

Since we are scientists, I decided we should confront our hypotheses with data, or at least with a non-random sampling of people on Facebook. Luckily, it turns out that people are always interested in talking about narwhals (something to keep in mind next time you’re in a social situation that requires small talk).

Here is a Google map showing the geographic distribution of responses.

As you can see, responses were heavily skewed towards the U.S. This brings up the first issue with the data: U.S. respondents tended to provide their location to state while European respondents largely responded by country. After consulting with Silvie, I’ve decided to leave the data as is (state level for U.S., country level for non-U.S.) given the size of European countries versus the U.S.

First, testing Nicole’s hypothesis: is there a relationship between narwhal knowledge and geography?

Age of first narwhal knowledge by distance to ocean (estimated very scientifically with the scale bar in Google maps).

Second, testing my hypothesis: is there a relationship between narwhal knowledge and career path?

Age first narwhal knowledge by career class.

As you can see, the data does not support either of our hypotheses. This has lead to follow up conversations, discussing research methodologies and generating alternative hypotheses (e.g. does parental career matter more than your own career?) Again, narwhals are a great conversation starter.

I also polled people on what the letter N stands for. This was mostly an excuse to try making a word cloud in R, but also one of the reasons that I think children learn about narwhals early is because they are often used to illustrate alphabets. Obviously responses were a tiny bit biased by the preceding questionnaire about narwhals but surprisingly, not everyone said narwhals.

Word cloud of what the letter N stands for in an illustrated alphabet.

1L of urine yields 6h of electricity

Though they'd be too young to drive a car in the US, I'm pretty sure these girls could take one apart and put it back together

For the third year in a row, innovators and inventors in Africa have been gathered together by the international organization Maker Faire Africa to share their ideas on how to solve pressing problems in their developing countries. This year, Duro-Aina Adebola, Akindele Abiola, Faleke Oluwatogyin, and Bello Eniola (14, 14, 14, and 15 years old) developed a device that converts something we don’t need into something we do- urine to electricity! (I think they should call it a “Power Pot.” Get it? Instead of flower pot? I bet MBT thought it was funny.)

Essentially, it filters and purifies hydrogen gas from the breakdown of urea and uses that to fuel a generator, to make the electricity. I learned all of this from an article that someone posted on facebook from The Next Web, but then found an article from Wired that was kind of a downer about it. The girls’ design might not be capable of generating a net gain in electricity…which is a bummer. Anyway, I just wanted to post this because I had never heard of Maker Faire Africa and wanted to spread the word about what seems like a great organization (in spite of their somewhat uninformative website). And also because I am awestruck by the young and ambitious (and mechanically-gifted).

I think my best idea when I was a kid- about 10, maybe?- could have been giving sick people healthy germs to make them better, but I never actually got around to testing it. Even though I felt like perhaps it actually was a good idea when I heard about fecal transplants (and, you know, all of the within-host competition work in the lab), I think I had been planning something along the lines of giving people spoonfuls of my spit, so I’m not sure that I really missed an opportunity to save lives there.

The Big Gulp

It’s a catchy phrase.

Despite the fascination of basic biology (e.g., the gorgeous mosquito below), we scientists often fail to explain what we mean without resorting to jargon. So it’s refreshing when researchers coin descriptive names rather than mysterious acronyms. It’s certainly not easy to avoid jargon when describing the life cycle of a complicated organism like malaria, which is essentially a parasitic algae that invades red blood cells and eats them up from the inside. Today I read about the “big gulp“, which is the technical term (really) for the process by which a thirsty malaria parasite takes a big drink of red blood cell. The parasite flattens like a pancake and the edges curve inward to seal around a large chunk of hemoglobin and goo (to use another technical term)–a big gulp that has been captured on film. If another group of researchers had been the first to describe this behavior, they might have named it “intracellular pinocytosis“, which would have been tragic. Nothing fails to convey enthusiasm for basic biology like dry terminology.

The Magic of Mosquitoes

With all this discussion of weebles, success,and impact (or the lack of it!) I can’t help, but wonder about why I’m in this business anyway.  I certainly want to help people, but there is often a long and winding road from the basic research I conduct to stopping cases of malaria or dengue. The reality is that my work might not help anyone, anywhere, ever.

I have one simple goal and that is to convince the vector biology community we should study mosquitoes as we would any other animal. Just because some mosquitoes transmit pathogens that happen to infect humans does not mean they forfeit the right to be complicated or are excused from evolution outside of interactions with us or the parasites we care about.

These animals lead fantastically beautiful and complex lives outside of transmitting diseases. I believe that by lifting the blinders and looking at these insects outside of their role as vectors, that we will find new ways to control disease. We will also have the privilege of witnessing new and amazing things; moments that make nature seem like magic.

The incredibly beautiful Sabethes cyaneus. Males of this species perform dances for their ladies to convince them to mate. Stolen from (http://www.flickriver.com/photos/tags/lalat/interesting/)

I’m thoroughly enjoying working on the interaction between malaria parasites and mosquitoes, but sometimes I pine for the days when my mosquito had no pathogens and I was simply asking, “What are you doing? And why?”.

I feel like I’ve been distracted from my simple goal.  Hopefully, someday I will get back to basics. NIH probably wouldn’t fund it, but it is the magic that drew me to science and it is the magic that will allow me to endure.

Weeble wobbles

Today marks the two month anniversary of my arrival in State College and the beginning of my postdoc in Matt and Andrew’s group. Not surprisingly, I’ve spent a lot of the past two months thinking about career transitions.

One thing I’ve come to realize is that moving to a new lab is a bit like being a Weeble. If you’re not familiar, a Weeble is an egg shaped toy with a weight in the bottom. When you push a Weeble, it swings around wildly until the heavy bottom brings it back to a stable and upright position. Likewise, when you transition between labs, some wobbling is to be expected but hopefully you too will eventually stabilize, thanks to your heavy bottom (or solid foundation, if you prefer).

Obviously career transitions are not unique to science, as most people switch jobs at some point in their lives. But in science, such changes are notably frequent and largely regarded as necessary. For example, I’ve worked in four labs thus far and my current position is, again, temporary. Even in a permanent position, turnover in a lab is so constant that you are still effectively changing labs every few years.

These transitions are so engrained in the scientific culture that staying on in a lab can be viewed as bad for your career. I’ve heard multiple times the advice that, when you do your postdoc, you should change at least two of three things: the institution, the study system, or the question. Presumably, the idea behind this advice is that broadening your experiences also broadens your thinking. Unfortunately, it also takes you out of a lab where you’ve spent a significant amount of time developing your skills and research projects, and sets you wobbling off into a new lab.

Likewise from the PI’s perspective, you put time and money into somebody only to send them away as soon as you start getting a return on your investment. As Mark Cohen wrote earlier this year in a letter to Science, “can you imagine a private-sector environment that demands of its best workers that they find jobs at other companies, rather than nurturing them towards the success of the business overall?” This observation makes me wonder if the frequent turnover in academic science plays a role in driving scientists out of universities and into the private sector.

All of this is not to say that I am unhappy in my new postdoc position. Despite the immediate cost to my productivity, I made the move because I anticipate a net positive in the longer term. However, I do think that it’s worth discussing the trade-off that comes with moving labs, and questioning whether the current emphasis on change really is best for many mentors and mentees, and for science in general.

Mastering the Art of Gametocyte Induction

Everything seems harder the first time you do it. 

If you’ve made bread, or, for you scientists, designed PCR primers, think about the first time you did it. On the face of it these processes are simple, and share the same formula; you have a recipe, you follow it, you get the desired product. End of story. Yet, acquiring new skills often doesn’t feel simple.

I usually have some apprehension the very first time I try something – will the bread really rise like it’s supposed to? – and experience relief, satisfaction, and the sense that I’ve experienced some small miracle when ingredients have been turned into a loaf of bread, bands on a gel, etc. But the magic wears off. Later, looking back, it’s hard to remember what the big deal was.

So what makes learning new skills seem difficult?

At least two things – feel free to add more:

1) How intrinsically hard it is. Let’s face it, some things are just hard (e.g. requiring many steps, background knowledge, complex movements – see “expertise“, etc).  This is related to the learning curve, or the difficulty of the new skill. Not much skill necessary to boil an egg, and quite a bit to design working PCR primers. For simpler skills, learning happens in huge leaps early on, followed by smaller gains as there is less left to know, whereas for harder tasks the climb up the curve is just one long slow haul.

2) Level of familiarity, i.e. transferrable skills. If you apply previous experiences new skills seem much easier: PCR aids learning quantitative PCR. And, we actually do get better and faster with practice; this looks a lot like improving efficiency along an experience curve to me.

Right now I’m learning how to grow Plasmodium falciparum parasites in culture.

I’ve been told this is really straightforward, and the basic steps for growing an asexual culture seem to be – plus they are relatively hardy little buggers. But I’m interested in the life stage that can infect mosquitoes – the gametocytes. These are the sexual stage, the prima donna parasites, finicky about temperature changes, whether they get human or animal sera, fresh or less-than fresh RBCs, you name it. Unfortunately, even the people that do this for a living have told me gametocyte induction is really hard.

Why?  Well, as best I can tell it’s a combination of slightly technical challenges (sneeze in your culture and it’s all over), and the need for experience to know exactly when to do each step. The parasites are only convinced to become gametocytes by being stressed. Without stress, the asexuals would happily keep on growing, and might never make any gametocytes. In practice, this means that after I get the parasites growing I’m then stressing them to the point where some inevitably die, more have a near-death experience, but not stressing them so much that the whole flask of parasites kicks the bucket. (I find the parasites aren’t the only ones a little stressed by this particular step). Afterwards I make every effort to placate them with a cushy environment, the freshest red blood cells available, and try to make amends (all while selectively killing the other non-gametocyte-producing stages with heparin). After several days only gametocytes are in the culture. This is way more involved than any bread I’ve ever baked.

Feeling about as comfortable as Julia at a too-small stove...

But, as Julia Child said, “Anyone can cook in the French manner anywhere, with the right instruction” (Mastering the Art of French Cooking, introduction). [Translation – “Even Jessi can learn gametocyte induction techniques with the right instruction”].  And fortunately I have the written instruction of many other scientists that have tried this. Much more importantly I have the expert instruction of the members of the Cui lab. In particular, Feng’s advice and patient explanations continue to be invaluable in this process.

Having mentorship in learning complex techniques is vital, and nothing beats actually seeing the process through when first figuring it out. It has allowed me to jump along the experience curve to become more efficient much faster than I ever would have been able to without this type of help. With luck, and enough observation and practice, I’ll be bringing this skill to the Read/Thomas group sometime soon. I’m planning to use the same equipment and tools since familiarity makes the learning process easier, and reduces room for errors due to picking the wrong types of flasks and so on.

When an expert isn’t available there are often alternatives – perhaps this explains in part the popularity of cooking shows, or youtube instructional videos. Scientists are cluing into this – just check out the Journal of Visualized Experiments.

This week my parasites are on their way to becoming beautiful gametocytes. In fact, the precocious ones made their appearance this afternoon! They should continue to develop, barring any hurricane-related interruptions to their care. I’ll keep you posted.

How do we balance respect for individual privacy with the demands of epidemiological research?

Human disease epidemiologists love Scandinavian countries. Not only are they delightful sites for conferences (side trip to Norway’s fjords, anyone?), they also maintain fanatically detailed health records for their citizens that they are more than willing to share with scientists. These datasets offer amazing opportunities for disease modeling and allow breakthroughs that simply wouldn’t be possible with less complete data. It’s much harder to do this type of work in the US. Our health records are incomplete, noncentralized and difficult to access. And when datasets are identified that do offer opportunities to bypass these problems (Guthrie cards, for instance), legal maneuvering by privacy advocates can make meaningful studies untenable.

As a researcher, I am awed by the potential of detailed personal health data to revolutionize disease management. We’re now able to track influenza outbreaks by analyzing Twitter streams; imagine what we could do with unrestricted access to Guthrie cards, computerized health records, network data from Facebook, GPS data from cell phones? But I also understand the perspective of the private citizen, who may or may not be informed about his data are being used, and who may be subject to increased insurance premiums, job discrimination or public shunning if these data are not properly handled.

Very few people would feel that private testing of infants for easily treatable genetic disorders is a bad thing. Likewise, very few would be comfortable with full public disclosure of all genetic data, health records and spatial information. But there is a huge gray area in between these two extremes that would respect individual privacy while allowing research to move forward. Public outreach and education, opt-in vs. opt-out programs and a firm commitment to privacy and transparency will increase public trust and facilitate scientific inquiry, but will this be enough? What kinds of safeguards and incentives do you think will be necessary to public health research forward in the US?

Success or failure?

Lauren asserted at a lab meeting a few weeks back that we (Matt and I) don’t talk enough about our failures. What was she thinking? Of course we don’t. We’re blokes. But three times, NIH refused to fund Lauren’s work, even though her idea is excellent, her preliminary data good, her track record excellent, and Matt and I threw our best grantsmanship at the problem. We fund her work anyway, and Lauren now has some great results. Hopefully, a story of success despite the system. But Lauren’s point was that as mentors, we need to equip our people with the right expectations.

It turned out Matt and I had no idea what rejection rates to train people to expect. The national statistics are not much help because many people write bad grants. What you want are the numbers for people who are competitive. Matt and I had no idea how well even we were doing, so we dug up the data for a subsequent lab meeting. The numbers dropped out like this.

We submitted our first US grant in May 2008. Forty two (yes, 42) grant applications later, our success rate per application is 48%. This includes grants we did together, as well as our individual efforts, or grants one of us did with other collaborators. If we break it down by project, and ask what proportion of projects we eventually got funded, the rate is 78%. That includes things we flogged away at repeatedly (worst cases: success on the seventh go, success on the fourth attempt). The proportion of grants that got funded first time was 31%. The proportion of eventually-funded grants that got funded first time was 63%. We abandoned only two of the submitted proposals as having no future or being too low priority. The remaining 95% of applications led to external funding eventually or we continue to fund them internally because we believe in them. Total cash raised? Somewhere between $27-$28 million, of which the share coming to Penn State is about $11 million.

Is that a record of success or failure? Hard to say. We now have a large well-funded group filled with smart people I like a lot. That feels good.

From the expectations point of view, there seem to be three lessons.  First, even senior people with much experience get rejected a lot. In this game, you need to develop the ability to absorb rejection. Second, raising money requires huge effort. A Gates Grand Challenge Exploration grant takes just a few days to put together if you know what you want to do. An NIH R01 application, especially one with complex partnerships, might take 6-8 weeks to put together the first time, but only once it is clear in your head. An R01 re-submission takes perhaps 1-2 weeks if it was in good shape the first time round. Putting all that together, Matt and I estimate that over the last four years, we have each spent at least a day a week raising money.

The third important lesson I realized only after the lab meeting. According to the post-docs I talked with, the most sobering insight was prompted by Matt’s comment that the whole process never stops. And it doesn’t. It is professional combat sport: highly competitive and very bruising if you do not have the right mindset. But in sport, it’s unusual to compete at the highest level for more than a decade. In science, winning means you get the chance to keep competing with the world’s best — for thirty years or more.

Science on the Hill: How science can work with policy-makers

Recently, a member of the House of Representaives Committee on Science, Space, and Technology made comments suggesting that human females could control internal fertilization (clip). Italian courts don’t seem to understand how to interpret a P-value. (see Katey’s post ). Politicians continue to fight about whether global climate is changing, instead of making policy decisions about whether we need to do anything about it.

There seems to be a general lack of understanding about the facts science produces, the processes by which scientists arrive at those facts, and what role science should play in policy. I find this trend deeply troubling. Scientists have clearly failed to communicate how we conduct science,  the methods we use to interpret results and the distinction between facts and opinions (interpretations of what our results mean) to policy makers. Attempting to bridge this disconnect seems impossible to me.

I have reached a place of complete frustration and think the situation might very well be hopeless. Clearly, I’m going to need help understanding the other point of view. I need to have a civil conversation with a Washington insider. I happen to know one and I think we can keep it civil. I actually love him. He is my dad after all.

Left, My father and I agree on many things. Surely we can have a reasonable conversation about a "real" issue. Right, Me at my father's desk assessing policy briefs circa 1984. Clearly, I've already had enough!

My father, Tom Cator, has worked on “on The Hill” for the last 36 years. He began as a staffer for the U.S Senate and for the last 30 years has worked as a lobbyist across a broad array of industries. We had a fairly long conversation about science on the hill this week. Here are the key points that we discussed.

“Follow the money.” Money is part of the reason that policy makers often will argue or ignore facts. For example, if most of your state’s income is dependent on oil and gas, you are not going to go on the record agreeing these industries have contributed to global warming. “Politicians often don’t come in with an open mind. Their view is often based on who paid for it and what constituents think.”

“They will try to take you down”. I posed a question, “So say a group of scientists descended on The Hill. We went door to door and we offered to answer scientific questions”.

My father responded to this with a slight sense of panic in his voice, as if he was imaging me running through the Rayburn Building with a mosquito net, “That won’t work. First, they won’t have questions for you. Presentations have to be timely, or appear timely, in a political context. Second, if your facts don’t support their agenda, they may go after you personally, attempt to impugn your credibility. They will find someone to poke holes in your research.

“Everyone has an agenda.” This was troubling. Facts are facts. Science is objective. You can’t just poke holes in research unless there are actual weaknesses. Why don’t politicians understand that? My father continued to explain that many times politicians think scientists are playing political games. “If you came to me with data, I would want to know what your agenda is”.
I countered, “Facts don’t have an agenda.”
Do they? Well, sometimes.
Over the last twenty years, there has also been a noticeable increase in “think tanks”  in Washington. This term is broadly applied to many organizations, but some of the largest are privately funded entities. Many times politicians get their research from these sources. “Think tanks have to pay salaries and rent. It’s a business. Where do you think they get their money? Industry, organized labor, wealthy individuals, interest groups, and others.” my father points out.

“It is bleak and getting bleaker.” Over his career, Tom has noticed a disturbing shift in how business gets done in Washington. “It used to be that congressmen would get facts from lobbyists. A good lobbyist would approach a legislator with their case, represent all of the facts and facets of the issue, and then would explain why their policy position had merit. If an issue like climate change had come up 20 years ago there would have been multiple hearings with recognized experts. There would have been a long discussion about the facts. There is no longer a comprehensive look at the issue.”

There has also been a shift in how legislators define compromise. “It used to be you would find points on which you could agree and disagree and meet in the middle. Now, compromise tends to be ‘I don’t budge and you meet me here’.” This change in attitude has made debate, whether scientific, legal, or moral, stagnant.

“Nothing moves quickly”.Policy does not change quickly. Within the next decade, Medicare is going to go bankrupt. They aren’t doing anything about that. You think they are going to jump on something like climate change? There is little effort to look at long term trends and how policy should respond. Statesmanship is needed.”

Acceptance of scientific findings is also very slow. “The system is rigged to not let real science percolate up, at least not in the short term”. We agreed that this was not necessarily a bad thing. Scientific debate and discovery moves very quickly. When we make policy decisions, we need to be very certain that the scientific debate is satisfactorily over.

“Strike back” At this point in the conversation I was not feeling particularly hopeful. How do we motivate these congressmen to listen and get something done?
“There has been a failure of science to address this issue.”

Politicians are in Washington to represent their constituents. If voters in their district care about something, then congressmen will care. “Getting the public, voters, and community leaders involved makes it much harder for a politician to walk away from facts”.

And then Tom got real personal.

“The academic community has fallen down. They don’t try to involve the public or policy makers. You live in a politically conservative county in Pennsylvania. What are you doing to educate your public on science?

Caught off guard, I mumbled something about public lecture series.

You can’t do it from 9 am-5pm. People work. What about continuing education at night? How about explaining how climate change is and will impact the farming industry in central PA?”.

I quipped back, “I don’t see how I can talk to people who don’t want to hear what I have to say”.

My father responded, “Find a reason for people to come and make it convenient for them. Go to a local high school science teacher and have her tell students, ‘Come to this thing tonight and you get extra credit, bring your parents and we will double it.’ Then present facts carefully and be as scrupulous as possible. Present work that has been rigorously peer-reviewed, and is complete and unbiased. Maintain objectivity and project a service. Engage them in a discussion.”

I do not feel anymore empathy for Washington, but I think this conversation did get my wheels turning. I have been going at this the wrong way. Changing the way science is viewed on The Hill needs to come from the ground up and it can start here with us. “The issue here is that we need to inspire constituents to become informed about science and communicate with their representatives.”

What if experts from CIDD gave an evening seminar series at State (or Altoona or Bald Eagle) High? What would the challenges be? Would scientists participate? Would anyone come? What topics could we cover? I have no idea how to answer these questions, but perhaps I should be thinking about them.

Tips, tricks and fixes from your favorite admin

Hola!

My second blog (my manstand-blog is banned permanently…) is to provide solutions to some common blogging problems. This means that this post will be updated regularly, to include to latest information that should hopefully solve your blogging problems… if your (blogging) problem is not described below, do email me!

Post-title not linking to post-page and ‘Leave a reply’ not working Katey noticed it was not possible to leave a comment on Eleanore’s blog. Me thinks the problem is that Eleanore changed her blog title after publishing the post (or saved a draft version without a title). WordPress works with ‘slugs’, a few words that describe a post or a page (if you look at the url of this page, you’ll see that the slug for this post is ‘tips-tricks-and-fixes-from-your-favorite-admin’). It will use your first saved title (or generate a number if there is no title). If you make changes to your title, the slug wil not update automatically. So … you have to manually update it in one of the boxes in the ‘edit post’ screen. You cannot use commas, quotes, apostrophes, and other non-HTML favorable characters. They need to be changed and a dash is put between each word. If you don’t see the slug-area, click on the ‘Screen options‘ (upper right corner) and make sure to select ‘slug’.

I tried to solve this issue with a bit of extra coding, but Andrew’s website completely disappeared from the world-wide-web (no worries Andrew, for a few minutes only).

I am sure there will be more issues to deal with soon. But great job so far bloggers! The website is still working 😉