Ron Currie Jr. would say everything. To some extent, this is true: everything could matter. As scientists how do we identify what does? And prioritize the things that do?

We live in a society where criminals are innocent until proven guilty, hypotheses are possible until proven wrong, and it seems like nothing matters until it does. Andrew shared with me an article this week on biases in scientific publications that discusses the trends of which we are all aware: negative results don’t get published, sex of subjects is rarely considered, and temperature and potentially important environmental factors are never reported. I agree with the author of the article that this is a problem. Much money and resources are likely being wasted testing hypotheses that have repeatedly given negative results. Negative-result experiments rendered their pursuers paperless while leaving future generations of scientists ignorant of what hasn’t worked in the past and what pet hypotheses they should get rid of before starting. When we suppress the sharing of negative results, I think we do a disservice to the community and forget the original rationale of starting the experiment. Experiments should not be started unless there is proper reasoning behind the hypothesis. Ethics should not allow animal models to be used if sound rationale were absent. This being the case, negative results should be informative and thus a helpful contribution to our field. However, as in journalism, television, and (most likely) life, our thirst for sensationalism quells that which we find boring. Negative results can be boring.

Boring-ness aside, there seems to be something else driving trends in research. We want to publish things that matter which brings me to the title of this post. What matters?

More and more review articles seem to be a call to arms for more complex models to consider parameters we previously ignored. Environmental factors, life history, age structure, immunity, social grouping, stress, the list goes on. If everything could matter, what matters most?

I think physicists have been struggling with this question since their field began. In Newtonian mechanics, if we knew exactly what mattered, we could theoretically predict every outcome every time. Because we don’t know what matters, we replace knowledge with probabilities based on past outcomes. In other fields of science, we theoretically should be able to predict the future if we know all the parameters at play (unless you are in the Heisenberg camp). The problem is figuring out the mattering from the not-mattering. In malaria, we don’t know exactly what matters in determining whether or not an individual will get sick. Until we do, how do we know what to report? How much of a problem is it that many studies have biased sex-ratios, poorly describe environmental conditions or use stable temperatures?

I think a solution could be found in doing more simple science to establish what matters most in the majority of model systems, and also in establishing better standards of reporting experimental subject and design details, especially by making use of online supplements. When we don’t know what could be important, I’ll agree with Mr. Currie and assume that everything matters.

The first time that somebody called me Dr. Sternberg was the day I defended. I was sitting on the floor in the hall outside the room where my committee was deliberating (or more likely, talking about something completely unrelated). The door opened, I sprang up, and my advisor held out his hand and said “congratulations Dr. Sternberg.”

That was over a year ago, and since then I can probably count on my fingers the number of times I’ve been called doctor. With the exception of e-mails from journal editors, the title is usually an instant spam flag in my inbox.

Like a number of my peers, I’m disinclined to use the title. Most of the time it’s unnecessary and, to err on the side of not coming off like an asshole, I generally don’t. The only time I use the title is directly following some obviously bad advice, as in “trust me, I’m a doctor.”

After attending a large conference this past week, however, I’ve decided that it might be time to start using the title more frequently. Not on personal communications or in situations where I might be mistaken for a medical doctor but next time I’m registering for a conference, I will check the “PhD” box. I don’t think it should make a difference in how people treat you but in certain situations – like at a big conference where everyone immediately checks out your name tag – it does seem to matter. If for no other reason then to avoid yet another awkward conversation where I have to decide if and how to politely mention that I’m not actually a grad student.

Bonus link: this post wouldn’t be complete without a reminder to brush that dirt off your shoulders.

It makes sense to me why a pair of pants (American English) is called a pair of pants.  According to a webpage I read once, in the original design of pants, people would where two separate fabric sleeves each called a pantaloon, and tie the two pantaloons together at the waist, thus making a pair of pantaloons, later shortened to pants.

But what I don’t understand is why the word “mathematics” is plural, or “statistics”, “physics”, or “economics”.  I would be able to accept that it just is, if it wasn’t for the fact that “chemistry” and “psychology”, for example, are singular.  To make things even crazier “biology” is singular, but “the life sciences” is plural.  Aren’t those just two different phrases for the same thing?  How can one be singular and the other plural?

If I was in charge of remaking the English language, I would demand more consistency.

Two gametocytes in the same red blood cell (bottom left) and two misery-causing forms also infecting the same cell (upper right).

What makes a good scientific story–also known as a publishable unit? I appreciate stories with nice, straightforward themes about how living things work, but my tastes run more to long and convoluted stories that capture a substantial chunk of the biological complexity. Those are the stories I try to write as well, and it does not go quickly. At the moment I’m hesitating over a story about how we measure what malaria parasites invest into transmission. It’s critical to know how much of the liberated host resources go into transmission: Malaria has specialized forms called gametocytes that get passed onto mosquitoes, but it’s the other parasite stages that make people sick. In other words, what parasites invest into transmission they cannot also invest into causing human misery. Unfortunately, it’s really hard to figure out what parasites are investing into transmission because we can’t identify precisely when parasites have committed to transmission–we can only detect parasites that have long since committed to becoming transmission forms. I have a model that provides a perfect opportunity to test out the ways we calculate transmission investment, and it suggests that we can’t say exactly what we want to about transmission, for example that parasites are investing 10% into transmission at day 8. I’ve been reluctant to start writing the story because I don’t know the ending. I’ve made an attempt to derive a more sophisticated method of calculating transmission investment, but it performed abysmally on my simulated data. I don’t want to write a story that says current methods are flawed, but that I have nothing better to offer. My plan is to write it the story as an opinion piece (at which point it should be clear how I should have written it). Please comment if you have any advice on opinion pieces, and once I have a draft I’ll be getting feedback from folks on whether I sound too much like a Debby Downer.

Last week was officially my last week as Andrew´s postdoc. Truly last this time round, though with much work still left undone, this won´t be a goodbye message. I´ve learned a lot over the nine (!!) years since I started in his lab as an MSc student. One of these things is to go out and network. I believe it is a very important skill in science. It is something that comes more naturally to some than others, but it is definitely a skill that can be learned, though it will require courage.

What will you do? Seize the opportunity or hide in the bathroom?

I again realized the importance of this during a meeting I attended over the past two days. It was a small international meeting on the topic of antibiotic resistance, extremely interesting. At the same time, I felt very much out of depth in this crowd of mostly clinicians, hardly understanding the field-specific language of abbreviations for any bacteria, antibiotic, mutation, cut off point they know. In addition, I hardly knew a single soul at the meeting. Would I have just attended the meeting, I would´ve learned some interesting facts about antibiotic resistance and some references to key papers. However, I gathered up my courage to chat to some important people over coffee break and asked a few questions that led to a long discussion over lunch with some other important people (one of whom, by the way, was telling me after I confessed I hardly knew anything about bacteria and more about malaria, that malaria research can have some really interesting insights in drug treatments in general, referring to our PNAS and PLoS Path papers, TADAAA moment!) and learned so much more. Now, I feel like these two days were time well spend (while I know I could´ve worked on important MS´s that need to get finished, I know Andrew…).

This networking thing absolutely doesn´t come natural to me. I have to convince myself that these other people won´t bite and my question surely can´t be entirely stupid. Still, I feel nervous and goofy when I am sneaking up to some ´silverbacks´ over coffee break to introduce myself and my heart is pounding out of my chest when I ask a question at the end of a talk. However, I have never regretted opening my mouth. So, here´s my advice to all starting PhD students, or even postdocs, that are afraid of asking questions or networking with strangers on conferences. Just do it. If you are planning to wait until you aren´t nervous about it, it will never happen, nervousness disappears with practice. Start with lab meetings, then try to ask a question during CIDD seminar. If you are worried that you might ask something stupid, or don´t know any question, use this trick: make yourself write up one or a few questions during every seminar. It will get your brain involved, and you´ll probably realize that often someone else is asking your question. Ask your question to other PhD students and postdocs afterwards to get your confidence up that you didn´t have a stupid question (which they never are!). Then one day, don´t think about it, raise your hand, and you´ll realize afterwards that the world still exists.

I truly think that actively participating in labmeetings, seminars and conferences will get you so much more than passively participating: not only will you learn more and generate new ideas, other people will get to know you and your thoughts too.

Well, so far my parting wisdom. Looking forward to seeing you all again (networking) at a future conference!

I like Marcel’s wisdom.

Three words. It’s that simple.

I’m writing this blog post because I’m stuck on the manuscript I’m working on. I’m attempting to address reviewer comments but many of the comments are open ended, which I’m struggling with because it requires my limiting reagent: good ideas.

When I bring this up to past and present advisors, I usually get a response along the line of “ideas are cheap.” That may be, but I still feel like what limits me is the number of good ideas I have in a given period of time. Worse, there is nothing that I can do speed up the rate at which I have good ideas. If I need to, I can power through a 12 hour day of lab work or sit down and type out several reasonable paragraphs on a given topic, but those things can only happen once I’ve had a good idea.

Sometimes talking to people helps back me out of a conceptual dead end, but I feel like I have to have something already formulated before talking to someone else. When I’m stuck with a collection of amorphous concepts that I need to synthesize in a novel way that pleases the reviewer, it’s hard to bring to another person.

So for now I’m going to go for a walk, I’m going to buy a cup of coffee, and I’m going to hope that I’m due for another good idea today.

Bonus link to a blog post on revising manuscripts: Chekhov’s Gun.

Earlier this month, Hopi Hoekstra gave a seminar on the genetics of behavior, a field she is expanding with her research on burrowing patterns in deer mice. In her talk, Hoekstra suggested that behaviors are heritable and, in the case of burrowing patterns, dependent on only a few key genes. Her research is considered revolutionary by many as it may help illuminate mysteries surrounding the origin of behaviors, and even personalities. The idea that certain behaviors could be linked to a few key genes has got me thinking about what these genes are and whether the inheritance of behavior is all that different from the inheritance of any trait. Are the genes actually coding for “behavior” or is the behavior an artifact of an inherited morphology or other trait?

Hoekstra suggested genes for dopamine receptors as being potential candidate genes that affect the burrowing behaviors she observed. But could there be morphological differences such as leg length, or musculature which also may contribute to a mouse’s burrowing ability? Could those few genes that appear highly correlated with burrow length actually be coding for physical traits which would then give rise to behavioral “artifacts?” This leads to the question of what is behavior and whether it is distinct from the physical traits we possess. I hesitate to agree with the idea that there are “behavior genes.” Rather, I wonder if we are confusing certain traits that are heritable with the behaviors that they may give rise to.

In 1958, Erwin Schrodinger wrote a book called Mind and Matter, which discusses the role that human consciousness plays in evolution (I put it on the list of “life-changing” reads). One topic he addresses, of particular interest in light of listening to Hoekstra’s talk, is the “genetic fixation of habits and skills.” Schrodinger’s perspective from half-a-century ago is not all that different from what we are potentially finding today in the field of behavioral genetics: behavior is heritable.  But Schrodinger says something more: behavior and physique cannot be separated. “You simply cannot possess clever hands without using them for obtaining your aims … You cannot have efficient wings without attempting to fly. You cannot have a modulated organ of speech without trying to imitate the noises you hear around you. To distinguish between the possession of an organ and the urge to use it …. would be an artificial distinction,” (p.121). Is behavioral genetics making a field out of this “artificial distinction?” In our own lives we could think of the behaviors we have and ask whether these behaviors are more likely to be a consequence of “behavior genes” or genes for traits that make us more likely to have certain behaviors. I enjoy running. Did I inherit a “running enjoyment” gene or is it more likely that I inherited genes for a certain leg-type? or certain endorphin-craving brain receptors?

Because most things make more sense with analogies (at least to me), I like to think of it this way: Let’s say we have a ball of play-do. It is spherical, smooth and malleable as a consequence of its structural makeup. We place the ball of play-do on an incline slope and it rolls. Is the rolling behavior independent of being round? Would we still see rolling behavior in a flat or frictious environment? Probably not. In my opinion, the quest for “behavior genes” is not different than the same quest we’ve been on for the last century: understanding the distinction and interplay between all genes, their expression and the influence of environment.

Dengue fever is caused by a virus primarily transmitted by the mosquito Aedes aegypti. The disease is not associated with a particularly high amount of mortality, but its symptoms are particularly unpleasant. The common name of the disease is “break bone fever” and it gets this moniker from the severe joint pain that often accompanies infection.  There is currently no vaccine for dengue and there is no specific treatment option.  If you contract dengue, you are given supportive care (fluids, ect.).

Envelope protien of dengue virus (Purdue University computer illustration)

Up until recently it was thought there were four distinct serotypes (differentiated by host response to challenge) of dengue circulating. Last week researchers announced that
for the first time in 50 years a new serotype of dengue has been detected.

This is bad news.  It makes vaccine development even more complex.  Any new vaccine will have to protect against 5 serotypes simultaneously.  If it does not there is a risk for cross reactivity in vaccinated patients when they encounter new serotypes. This cross reactivity is thought to be a contributing factor to the emergence of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), more severe forms of the disease that include internal bleeding. It also introduces additional complexity into an already complex public health problem.

However, it also represents an amazing opportunity.  The new serotype has only recently emerged and for the first time researchers might be also to trace back this emergence to determine what factors contribute to the making of a new serotype. How did this new serotype interact with mosquito hosts, wild monkey populations, and humans along its way?

I started a reply to Andrews post on open data which turned more into a blog post in it´s own right. I am a firm believer in open data. That is, after you are done using it. I´ve never been a hoarder, and if I can make someone happy with something I don´t use anymore, great. With data it is even better, as it is more like sharing. It doesn´t mean you will not be able to use it yourself anymore either; I think the chance that someone else will do exactly that with the data as you were planning on doing is rather slim. The chance is greater that someone will do something with it that you either (i) would have never thought of, or (ii) don´t have the right toolset to do so. The net result is likely that you will learn new things.

The downside that I see is that numbers in an excel file alone may be insufficient to fully understand the data. I know this data. They are my babies. I spend numerous hours with these mice and parasites to generate the data. I´ve pipetted more tubes and plates than I can count. I know the peculiarities and sensitivities of the different PCR assays, the history of the parasites, the behavior of the mice and the mornings when Derek was sampling hungover. Moreover, I have thought about this data a lot, under the shower, during a run, in my sleep and during romantic date nights. That is not to say that other people won´t be able to make sense of it. It does mean that I believe I might be able to add useful insight in any observations that anyone has.

So, if anyone ever wants to use my data, please, be my guest! It is satisfying to know that my hard work is still useful for someone else. However, I would be happy, and encourage everyone, to start the dialog too. What is your interest in the data, what are your observations? Let´s have a discussion and together increase our understanding of these infection dynamics, which is, after all, every one´s aim.

In the spirit of appreciating good science journalism (and not just complaining about the bad), I found this neat article about science inspired by science fiction. Apparently folks have gotten surprising close to telekinesis via helmet, the repelling gun favored by Batman, and getting photons to interact in ways that might lead to the development of light sabers (practical applications to follow–I can’t imagine people really using it to mow the lawn). All science must be preceded by science fiction, even if people don’t bother to write down their complete chain of what-ifs. My favorite papers are simply well-reasoned sci-fi.

It’s hardest to see the pieces that are missing, and I particularly appreciate papers that examine the life strategies we don’t see. For example, Hurst’s “Why are there only two sexes?” gave us solid expectations about the number of sexes we should expect on this and other life-bearing planets (spoiler alert–it’s two). The downside is that now I can’t help but complain of a lack of realism in any sci-fi that describes aliens requiring more than two sexes to get offspring (lots of Star Trek, Alien Nation, and so on). Now we have a nice mathematical model to show that requiring three or more players is just silly. More relevant to life on this planet is Day, Mideo & Alizon’s “Why is HIV not vector-borne?”–asking what constraints keep HIV from doing everything well. I feel that if I knew just a little more about the evolution of immunity with respect to body size, I could write similar paper about why we don’t see true parasitoids of large animals. There are blowflies, yes, but while they lay eggs in human flesh, they do not burst out of a person’s chest Alien-style. Not to sound ungrateful, but why not?

Blowflies aren't nice, but it could be much, much worse.

Might be a good question to ponder as the space-tourism industry starts to get a foothold…

The other day I was watching television and during one of the commercial breaks there was an advertisement for a new cologne, but no attempt was made to explain how it smelled.  So what I’m left wondering is whether I am expected to buy the cologne because I recognize the name or whether I am expected to buy it because a company executive had enough faith in the product to invest advertising dollars into selling it.

I think it’s the latter.  Companies have a limited amount of resources to invest in advertisements for various products, and so they have to prioritize advertising the products that they think can be successful.  Does this make tv ads a form of honest signaling?

Interesting thoughts here on lab bonding. No mention of curly fries.

The first step of the scientific method is to ask a question, a step which is prompted by observations. Observations depend on an organism’s limited senses, which in humans disproportionately emphasize detection of visual stimuli. When I think of the questions I ask myself before starting an experiment, they are usually prompted by things I see. A recent article in Nature Neuroscience suggests that when we devote our attention to visual perception, our brains selectively tune out other sensory input (we are not as good at multi-tasking as we think). By favoring visual phenomena, we necessarily start ignoring other senses. If science is prompted by the things we perceive, on a larger scale this has implications for what becomes the focus of our field, and, consequentially, what we may still be missing. What questions would we be asking if we were bats?

In 1989, Marion Isabel Newbigin wrote a short book, Color in Nature (the e-book is free to download) which discusses theories relating evolutionary biology to color and the impact abiotic sources of color (our blue sky, clear water, gray rocks etc.) have on the biological. I got stuck on the following quote: “[Colors] attract [the scientist’s] attention because of their frequently intrinsic beauty and their arrangement into patterns and markings which may exhibit extraordinary constancy,” (Newbigin, p.2). Colors certainly attract our attention but could they also distract our attention?

Newbigin provides three reasons why an understanding of colors in nature may be important: 1. The “conspicuousness of color in natural phenomena,” 2. potential links between color and evolution (as an important phenotypic trait), and 3. use in comparative physiology (e.g. are cantaloupes and pumpkins the same color for the same reason?). I agree that observations of color could spark interesting scientific studies, but it also seems to me that conspicuousness could be dependent on perspective. Colors that seem obvious, and a potentially strong selective trait, to highly vision-centric humans might not be selective for organisms interacting with less visually-minded community members. Do trees see their red fall leaves as conspicuous? WD Hamilton famously hypothesized that red fall leaves serve as a warning signal in defense against insects. But a 2007 review article in PLOS Biology suggests that that idea is dependent on the insects being able to detect color as a warning signal. Are the brilliant reds and yellows perceived by insects as a warning, or are they only wowing us humans? An interesting debate to have while the fall leaves outside MSC are in their explosion of color.

Watch this (sorry I can’t pause it and talk you through it as Eleanore suggests, but I have great faith that you will pay attention)

The first time I heard about these little guys I was quite amazed, but this is not such an unusual plan. Even within the mosquito family there are a wide range of foraging life styles. Larvae of the Toxorhynchites mosquitoes eat other mosquito larvae so effectively that they are sometimes used in control. They are not a particularly sustainable control option because once they have finished eating other species they will turn on one another.  As a result of this life style they are both gigantic as adults and do not blood feed as adults.  Just to be extra interesting the females of this species never land to lay their eggs.  In fact they do a special “oviposition flight” in which they conduct 6-43 elliptical loops before dropping them off (Collins and Blackwell 2000).

male Toxo

To learn more about this interesting group of mosquitoes go here!