Just thought I would post some high points from a lunchtime discussion on the stressful but character-building exercise of developing an elevator pitch to present at our six month review lab meeting. It makes sense to have a plain-language summary of one’s research, but it’s impossible to make a single pitch for a wide range of potential audiences. As noted in the links from Eleanore’s blog post, the pitch should change depending on the audience. We give our elevator pitches to the lab group–and believe me, I really appreciate having a kind audience already familiar with my research–but it doesn’t necessarily prepare us for the terrifying reality of elevators.

So here are two terrifying potential solutions:

(1) Rather than having a single pitch we give to the lab group, how about making cards with a potential target audience and each drawing one from a hat? Perhaps along the lines of “skeptical member of the public”, “family member”, “visiting seminar speaker” or more optimistically “Bill Gates”, or “talk show audience”. The upside is that we could have a lot of fun with the names we put in the hat (and I already have the hat), but the downside is that we would have to invest a lot of prep time.

This elevator contains only three people, rather than an entire lab group.

(2) Another option would be to draw names of fellow lab members and give an elevator pitch on their research. For one thing, it’s a lot easier to sum up others’ research, but for another, it would be nice to get an outside perspective on what research questions are most memorable and exciting. One possible downside: if it’s embarrassing to give a bad elevator pitch on my own research, it would be worse somehow to give a bad summary of lab mate’s research.

Or perhaps elevator pitches are an activity best practiced in the pub (and in small groups), in which case, the curly fries are on me.

Drug resistance is a problem. We can measure the devastation multi-drug resistance causes in financial figures and mortalities, and they all drive home the same point we focus on in our research day-to-day and which Andrew brings up in his class and TED talk: evolution is killing us. Antibiotics, antimalarials, cancer drugs, antiretrovirals, all have the same story. In malaria, it is a problem that has rapidly emerged after implementation of every drug we have ever brought to market. It seems like the explanation is simple: human intervention via drugs exerts selection pressure on bugs. The more drugs we use, the more pressure we are putting on bugs to evade them. But here is something I don’t understand: many, if not all, of these drugs were developed to mimic active ingredients in medicinal plants that we used centuries before the existence of big pharmaceutical companies. Why did resistance to the plants (and their active compounds) not develop over this time and interfere with their functionality before we brought them to market via big pharma?

Artemisinin has been in use for 2,000 years. We have found “prescriptions” for artemisinin in malaria cases from the notes of Chinese herbalist Li Shizhen — in 1596 he wrote that fevers should be treated as follows: “take a handful of sweet wormwood, soak it in a sheng of water, squeeze out the juice and drink it all,” (Meshnick 2002). Sweet wormwood, qinghao, is the same plant source we use in modern day artemisinin therapies: Artemisia annua. Evidence of artemisinin (ART) resistance and treatment failure is recent, with WHO issuing an official emergency response for containment of ART-resistance in 2013. Two thousand years of herbal use led to no problems, but less than 30 years of pharmaceutical production, and we have huge problems with resistance.

Artemisinin is not the only antimalarial that has this story. Quinine resistance also followed from the introduction of pharmaceutical production despite having long-term use as a traditional medicinal in its plant form. Why this trend?

I can come up with several possible explanations:

1. Maybe the concentration of active compound in plants is much lower than the concentration put in a pill that we can pop. That would translate to a lower selection pressure and a lower probability for resistance to emerge.

2. Maybe drug resistance did exist in populations chewing on cinchona bark (the source of quinine), etc., but without the abilities we have now to document treatment responses and genotype parasite profiles, we lack historical evidence for resistance to medicinal plants.

3. Maybe access to medicinal plants and the knowledge base of what plants to use was not widely spread, consequentially there wasn’t the same degree of pressure for parasites to evolve resistance as there is now. (This seems doubtful. If you have ever traveled to an area where traditional healers are more common than allopathy, the knowledge is as widespread as our use of chicken soup for a cold.)

4. Maybe plants and their synthetic or pharmaceutical derivatives from geographic regions more distant from a population are more effective than that population’s native plants and derivatives. For example, we could ask: have areas where the cinchona tree is native developed resistance to quinine more rapidly than areas where the plant is not native? If the answer is yes, than resistance to quinine may have already been developing under use of the plant, and thus emerged quicker where the trait was already present in the parasite population at the time of quinine introduction.

5. Maybe there are other compounds in medicinal plants besides the one active ingredient we tend to isolate that make plants “evolution proof.” Could medicinal plants be similar to combination therapies and we are not considering all possible components plants contain in terms of their antiparasitic abilities? Are we missing something when we isolate an active component?

6. Maybe synthetic versions are less potent than the natural plant because of differences in d vs. l enantiomer concentration. In vitamin E we know that the vitamin extracted from the plant is much more potent than the synthetic version because of differences in stereochemistry. It has so far been impossible to make a synthetic version that is not a racemic mixture. If the body recognizes synthetics vs. natural forms of the same compound differently, maybe synthetic antimalarial compounds could also be exerting a different selection pressure on parasites, leading to drug resistance?

A recent article in PLOS ONE may convince you that hypothesis #5 has some validity for explaining why artemisinin resistance appears to be a recent development despite long-term use of the natural plant. The study by Elfawal et al compared treatment responses between whole plant powdered leaves of A. annua (14.8 mg artemisinin per gram of dried leaf) and a comparable dose from pure drug. The results showed an obvious discrepancy in effectiveness, with whole plant treated mice having lower parasitemia and faster parasite clearance. Only when the dose of pure drug was at a dose five times higher than the dose of whole plant was the outcome of treatment comparable (24mg/kg artemisinin in whole plant treatment had the same outcome as 120 mg/kg of artemisinin pure drug).

This result suggests that either artemisinin in whole plant form is more potent or there are other compounds in A. annua that act synergistically in treatment accounting for the reduction in efficacy of the artemisinin pure drug.  The authors provide evidence that either possibility could be occurring, citing work that has shown that artemisinin in plant form is more bioavailable and that there are also particular flavonoids in the whole plant that could contribute to synergism. If flavonoids or other molecules in the whole plant are contributing to the enhanced potency, the authors suggest that whole plant therapy may be more similar to combination therapies currently in use rather than monotherapy with artemisinin.

Our current understanding of resistance suggests that resistance is less likely to emerge to a particular drug when used in combination with other drugs as the likelihood that resistance to multiple selection pressures occurs at once is less than the likelihood of resistance emerging to just one selection pressure, particularly if there is a fitness cost to resistance mutations. This has led to current implementations of combination therapy in treatment for HIV/AIDS and malaria. It looks like nature may have come up with this idea well before our antimalarial combo drugs. Is A. annua the original combination therapy? And is that what delayed resistance to artemisinin compounds for 2,000 years?

Seems to me like plants may be smarter than we think.

Source: Meshnick, S. R. Artemisinin: Mechanisms of action, resistance and toxicity. International Journal for Parasitology 32 (2002): 1655-1660.

I often complain about the cold weather, but I keep finding little elements that make life in the frigid cold bearable and at times increasingly beautiful.  I’ve become fond of going out on a run in the middle of a light snow at a nearby trail that runs through a wooded area near where and I live, and listening to the shockingly quiet landscape, or marveling at tree branches encased in ice after a freezing rain.

More recently, I discovered an extra treat that really appeals to the five year old in me. If you haven’t thrown a rock at a frozen pond, you need to do it promptly because the sound that comes from the act is devilishly satisfying.

I’m not the only one to think so. Check this soundclip out.

It did feel slightly blasphemous to have my first experience of this be at Walden Pond. I could just see Thoreau shaking his head in annoyance, “Darn kids!”.

For Christmas this year, my cousin bought me a rubber chicken.  It’s a great gift, as evidenced by the fact that I brought it into work my first day back and it’s been on my desk ever since.  But it also made me realize that I need a better way of communicating what I do to a non-academic audience.  In my cousin’s eyes, I currently work on chickens; I used to work on caterpillars; I might work on fish, or pigs, or (my mother’s fingers are crossed) humans in the future.  And my cousin’s view isn’t unique.  My family and most of my non-academic friends see me as a chicken biologist or an entomologist, even though I have never and would never describe myself either way.  I’m a disease ecologist.  I study the mechanisms that drive infectious disease dynamics.  Only by exploring multiple host-pathogen systems can generalities be made, and in my personal opinion, making correct generalities should be the goal of research.  I need to find a better way of getting that across.

On Wednesday, Andrew showed me a secret message. Well, ……… “secret” might be a slightly fantastic representation of the truth. The message is in plain view for all to see. It’s printed in large colored blocks on the carpet of a room on the 3rd floor. This message, however, IS written in code. Binary code to be exact.

At first I was a bit concerned that I’d been misinformed. There are 5 different colors arranged in what may or may not be considered a pattern. This led me to briefly consider some kind of “pent-ary” code but then I decided to focus on why five variables might be required to represent a binary code. Writing a full message in binary code would require a lot of carpet, so perhaps the 5 variables are used to compress the code into something that will fit in the room?

Now, looking at the carpet it seems safe to assume that the color brown is used as a spacer to mark where a word begins and where it ends. This leaves 4 colors: red (r), light blue (l), dark blue (d) and green (g). One possibility is that instead of printing all the 1s and 0s, only the 1s are recorded. In this case the colors could indicate the position of the 1 in a byte. This would allow long strings of binary like “00110” to be represented with the spatially more efficient “gd”. (Here I’ve assumed that green (g) is the 3rd position and dark blue (d) is the 4th position, which gives 2^3+2^2=12. The 12th letter being L.) Four colors allows us to represent 15 letters and since the final 11 letters of the alphabet are “pqrstuvwxyz”, it seems conceivable that a message could be written using only the first 15.

The code I’ve just constructed has a number of short-comings ………. the most important one being that it doesn’t seem to be the solution! But, now that I’ve spent a few minutes thinking about this I’m rather curious as to what the actual solution is and would welcome suggestions. Stop by my office (W244A) and let me know if you have any thoughts ………… I might even buy you a coffee!

I spend a lot of time worrying about what programs I use. Am I using the best programs for the job? Is it worth paying for a better program? Will people judge me harshly if I code in a less-than-optimal programming language? Some programs can be looked down upon (“why would you have chosen to write that code in Mathematica? It’ll take forever to run…”, and so on), perhaps for good reason, perhaps not. For example, I started out running models in Excel, and I still think it can be a relatively painless way to start out in programming. Unfortunately, it’s really hard to input complex models and error check, to make visually-appealing graphs, but people make do. Some use Excel by default, and some choose to challenge themselves by doing their work in Excel.

This Powerpoint rendition of malaria parasites bursting out of a red blood cell took a long time to make, but it was totally worth it.

As I’ve learned from Penny Lynch’s impressive Christmas cards, Excel can be used to create complex visual art too. In fact, there’s a contest for visual art in Excel, and the winning artist takes it to a whole new level. If Tatsuo Horiuchi can create exquisite art pieces in Excel (not Powerpoint, but Excel!), surely I can spend a little extra time refining the visual representations of my research. I’ve come across a few blogging scientists who take their presentation-style very seriously (fun blogs to follow: Neurodojo and Better Posters), and who feel that it’s very difficult to create good presentations and posters in Powerpoint. They’re right of course, but rather than invest in Illustrator, I think I’ll take a cue from Tatsuo Horiuchi and learn how to work magic with the programs I’ve got. It’ll be character-building, I’m sure.

It is cold today. It is single digits cold in Fahrenheit, or double-digit negative numbers if you measure how cold it is in Celsius. Here’s a silver lining; if you go for a walk you’re not going to be bitten by mosquitoes. Mosquitoes are typically active above 50°F – what do they do in weather like this?

They have three options for overwintering. 1) as an adult 2) as an embryo from an egg laid in wet mud 3) as a larva in water (plus option 4 – don’t live in a cold climate).

Option 1 only works for female mosquitoes – apparently the males either can’t store up enough fat reserves to go into diapause through the winter, or it isn’t worth it from an evolutionary perspective if females can bite and make eggs in the spring without them. It seems that if the males don’t make it that females must be storing sperm during this time too, at least some of them, or winter would solve our mosquito problems for at least some species. Females will switch their food source from blood to sugar-heavy nectar and rotting fruit in the fall to start building up winter reserves. Then, they hide out in woodpiles, under rotting leaves, in tree holes, nooks and crannies along riverbeds, anyplace out of the way where they won’t be disturbed. If they are really cold they won’t move at all when disturbed but reanimate when it is warmer.

Option 2 works because eggs laid in the summer aren’t as bulky or as well-provisioned as those that are laid for overwintering. These eggs hatch with warmer temperatures.

I only found one example of Option 3 – which was Wyeomyia smithii, a mosquito where the larval stage uniquely overwinters inside of pitcher plants. Apparently even when they are frozen solid they can reanimate and start feeding with warmer temperatures.

Doesn’t it make you feel all warm and fuzzy inside to know that even in these freezing temperatures the mosquitoes will be okay?