Modular design versus great hair

I feel that part of my role as an evolutionary biologist is to be critical of other species’ life-history decisions. It’s not as judgmental as it sounds–if a species is still around it probably is or recently was adapted to its environment. Malaria parasites make a lot of questionable life-history decisions (taking a really long time to mature inside the mosquito, synchronizing their life cycles within the host), but they appear to be extremely successful so their strategy can’t be all bad. I have some theories about malaria, but I can’t figure this one out:

Welwitschia mirabilis is not like other plants. Instead of growing an indefinite number of leaves that each have a characteristic size and shape, it produces only two leaves over its considerable lifespan (1500 years?!). These two leaves grow out like hair for the lifetime of the plant, showing truly impressive split ends. I think of modularity as a major point in favor of the plant lifestyle–if leaves get damaged by insect herbivores or careless mammals, just drop those and grow new ones.  Why would a plant benefit from giving up modular growth? And yet these plants continue to grow in the desert, in no imminent danger of extinction.

A Favorite Moment

Most of the formative experiences of my adult life occurred while doing fieldwork in other countries. A majority of that time was spent alone. This time spent alone has left me with many memories and feelings, both good and bad, that I continue to sift through and make sense of.  I thought I would share one of my favorite moments.

It was 5 am. This seems like a terribly early time to go for a run, but in Tanzania the sun has already come up and the back up generator turned off at 8 the night before so you’ve been in bed for ages when 5 am sun wakes you.

I was running down a red dirt road that cut through thick forest and I was already wet with perspiration.  Even at this early hour the air is hot and thick.  I ran past little houses constructed from wood and mud while women in brightly colored kangas watched me from their doorways. I huffed my good morning. They nodded theirs. Eventually the road narrowed and I was alone.

My beloved i-pod had died the night before so I was able to hear the bicycle coming up behind me. The chains jingled and the rusty gears creaked. A little boy pedaled past me.  He was probably 10 and he had to stand to pedal the bike, which was far too big for him.  It was loaded down with large bundles whose contents were obscured by the plastic tightly bound around them with rope.  As I was marveling at the little boy’s heavy
load, he was apparently marveling at the crazy blond woman running in the morning heat.

A cacophony of metal on metal rung out as he rode straight into a ditch.  His oversized bike fell over.  And then there was a pause. I swear I think that in that moment there were not even birds calling.  Our eyes met. On his face was a hint of embarrassment, but mostly terror.  Anyone who has seen me try to run in heat knows how terrifying I can appear.  It is a big blotchy Norwegian mess.  I’m sure I looked truly scary.

I stopped running and approached him.  I gave my best smile.  I used my best Swahili to soothe him.  It didn’t help. He didn’t move. He was terrified.

Moving slowly and gently, I started to lift the bike. Upon trying to lift it, I realized how unbelievably heavy it was. The boy joined in. Still we were struggling to balance it so that he could resume his tenuous position.

That is when it happened. They appeared like magic.  A dozen tiny hands belonging to a half dozen small Tanzanian children who had been watching us. Together we righted the bike and held it in place so that the little boy could reposition himself at the handle bars.  Together we jogged along side him to help him get some momentum and then we all let go and he glided away. He turned around and flashed a huge smile.

We all stood together for a moment watching him disappear and then, without a word they crept back to their yard, and I started my jog again. I can’t quite put my finger on why, but in that moment I knew the world was a good place and whenever I think of it I smile.

“Red Queening” the literature

My father likes to tell stories.  Some are better than others, but one that stuck with me was from when he was a physics major in college.  He recalls being at the university library and browsing the physics research section.  Back then (at least as he tells it), there was an annual publication that contained every physics paper from the previous year (apparently the term is omnibus (Mideo personal communication, Feb. 15, 2013)).  As he looked over the bookshelf, he was shocked by how quickly the thickness of the omnibuses increased over the years, ultimately splitting into two volumes, then three, then five.  He recalls thinking, how could anyone keep up anymore?  Project forward twenty or so years from when my father was in college, and people could still simply get away with reading the table of contents of the few most relevant journals to them.  But now, with so many new and general journals and so many publications, that seems inadequate.

Keeping up with the new literature, in my opinion, is one of the toughest challenges in science.  It is also critically important to doing good science.  On top of that, I find it terribly embarrassing when I am talking with someone about my project, he or she asks me if I have seen the new paper by so-and-so, and I have to say “no” and have the person explain the paper to me.

My current method for keeping up with new publications is to use the ‘alerts’ feature on Google Scholar.  Based on key words, I receive an email with the most relevant-to-me new entries in Google Scholar about twice weekly.  I have been generally happy with it so far, having used it for about three months.  About half of the papers (~ 50-100 per week) are relevant to me, which feels like an impressive ratio of relevant to irrelevant papers.  My big fear, however, is that I am missing many important things.  Unknown unknowns.  So what I am looking for are alternative methods to find relevant papers so that I can estimate how much I am missing.  How do you keep up with the literature?

Penny Lynch PhD

Today, Penny Lynch became Dr Penny Lynch. This is truly astounding achievement. She broke records for a member of my group. She was my oldest PhD student (by more than two decades). She was the last student I will have at a British University (I left 5.5 years ago). And she took 8 and a bit years to finish, the longest PhD I have supervised. But during that time, her productivity was up there with the best of my students. She published two papers as lead author (1, 2) and was a key player in one of my more important (3). Two more papers will come from her thesis, one of which could be a game-changer. She is a major collaborator on papers with post-doc Lauren on parasite manipulation of host behavior and PhD student Katey on new work on the Dilution Solution. She has collaborations running with two groups elsewhere in the US, and I am hoping to add a third.

What is amazing is that while she was doing all that PhD work, she also did her day job (City of London financial modeling), raised two gorgeous daughters (one just left for university), maintained a huge rambling, seriously ye olde house (16th Century?) in one of the most expensive parts of Britain, did some stained glass window construction (she is seriously weird) and sustained a marriage with one of the most understanding, supportive husbands in the universe. I lived through my wife doing her PhD, when we had no kids, no house, no financial obligations, no day job. And it was tough. Tom: thanks.

Penny is, I think, my 22nd PhD student. I have enjoyed her completion more than any other. When she first came to see me I guess about a decade ago, I never thought she’d make it. It really helps that she is one of the smartest people in the business. But more impressive, she is one of the most motivated, tenacious, and time efficient. And: we had a lot of fun along the way.

Revisiting “Work” and the American Dream

I come from a long lineage of hard workers and self-made men. My paternal grandfather, half-Cherokee, half-white, spent his life struggling as a traveling salesman in dust bowl-ravaged Oklahoma and Texas. My maternal grandfather has owned and operated his own business as an auto mechanic for nearly fifty years, and still works to this day, despite being in his late eighties. My father, a USNA grad, poured his life into working his way up the corporate ladder to an executive management position in a defense contracting job, only to be let go 18 months ago. I am my father’s daughter, and I carry with me many of the traits that brought him to success, good and bad. And because I share such a close connection with him, the failure, impotence and worthlessness he felt upon losing his job hit me excruciatingly hard.

I’m sharing this with you because I am terrified of failure. More so, however, I am terrified of being seen as anything other than a hard worker. It was difficult for me, last week, to listen to Courtney advise me that I “take a break” from experiments for a while, and take a few weeks to sit alone with my data and think. It was difficult, because I didn’t grow up in an environment where it was impressed upon me that being alone with your thoughts and taking time to mull over each passing idea was “work”. That isn’t to say that my aforementioned family members were thoughtless drones, and I do know in my rational brain that “thinking time”, whether it be an hour or a few weeks during a write-up, is indeed work. And at times it can be grueling, painstaking work. But, despite the fact I’m a year and a half into my PhD (and even gearing up to write my first manuscript), I feel as though it will take some getting used to in order to come to full appreciation (and admiration) of my thinking time.

I’m not sure if this is an American affectation, where, despite the quickly changing work environment that is shifting daily from office space to working from home, and classroom space to online education, we still associate “work” with some physical, tangible presence and a laborious “doing”. Perhaps it is simply an affectation of growing up in a culture of blood-sweat-and-tears blue collar workers and ladder-climbing corporate execs. Perhaps it is because the culture of work that is ingrained in me does not mesh smoothly with the culture of work in academia and science. Please don’t misunderstand, I don’t resent my upbringing, and I deeply admire those who shaped it to be what it is. However, as one of many first-generation American scientists with very similar pasts, I find myself constantly having to divorce myself from what our society has cultivated as the (rather masochistic) American Dream, and appreciate the labor of thought, and revel in the fact that work doesn’t have to be painful.

Now, please excuse me while I read Miller’s “Death of a Salesman” for the fifth time.

Danger Zone

How generalizable are biological theories? To what extent are they helpful to have?

How has virulence evolved? What explains plant biodiversity patterns in the tropics? How is climate change affecting ecosystem function?

Questions like these have spurred huge debates that continue today, and although for the most part concession has been reached that a single theory can rarely be all encompassing, there remains a lingering desire by many scientists to produce theories that are heavily inclusive of a variety of taxa and systems.

I cannot help but get into internal debates about the importance of forming “laws” in biology. Preconceived notions of how biological systems evolve can lead to inadequate intervention strategies, whether they be public health related or rooted in environmental conservation. For example, we have seen the failure of species introductions to control pests and the driving of multi-drug resistant pathogens. So what about the successes? Some of them have been luck, but I would also like to think that they have been a result of efforts to realize the intricacies of the particular system and the discovery of surprising components.

Making broad biological statements is not only an exercise in futility at times, but can also be potentially harmful. The complexity of specific systems must be picked through especially if there are elements that are counter to the current most popular biological theory. That will allow us to better, but not completely, anticipate the evolutionary outcomes of a particular intervention.

I think this needs to be a universal understanding among scientists especially in the current era where we see that the dynamics in the biological world are changing and people are calling for a reversal of human-induced effects. If humans are intent to intervene there absolutely must be a perquisite for understanding the system-specific details. Broad generalizations will not be sufficient and could be potentially disastrous.

A slow-burning question…

I do love symmetry. It’s not so much that I really believe that all organisms should have nice equal ratios of A, C, T, and G in their genomes, but why parasite genomes are almost as a rule AT rich has bothered me for a long time. As far as I know (and I might be wrong) there isn’t a good explanation. Some parasite genomes are ridiculously, even wildly AT rich. Malaria parasites are all AT biased, but to give one example: the genome of Plasmodium falciparum comes in a whopping 75% AT in coding regions and up to 100% in non-coding! AT nucleotide bias is found even in ectoparasites, like the human body louse (72% AT).

In fact, this AT bias is so common that specific methods are being developed to deal with associated genome sequencing problems, such as no place for primers to grip – those lovely GC “clamps” necessary for good PCR primers to stick are few and far between in many parasite genomes, and stutter error as DNA polymerase struggles to read something like ATTATTTTTTTTATAT and loses its place. However, in this same paper the authors casually mention that the pathogen that causes tuberculosis is super GC biased, and that’s what blew my mind and prompted this blog.

I had rationalized AT bias in parasites, and had even thought up some hypotheses that might explain it. Maybe it’s driven by chemical structure; the bond between A-T is a weaker bond with only two compared to three connections between G and C. Could this mean if there was competition between strains of parasite, the one with the speedier replication might have a selective advantage? Related to cost and speed: maybe A’s and T’s are cheaper to manufacture (smaller molecules) so the parasites can get more progeny for the same amount of host resources. A “bang for your buck” hypothesis if you will.

Perhaps the same “problems” for genome sequencing that cause more replication errors are somehow advantageous for parasites if rapid evolution (say for drug resistance) is difficult to achieve? Or, an entirely different idea: maybe DNA degenerates predictable into A’s and T’s over time. It seems some authors accept this is just the way evolution works, stating for example, endosymbionts with long associations with their hosts tend to be AT biased and using AT bias as evidence of a long association. If this were true shouldn’t all species that have existed for more evolutionary time have greater AT bias in their genomes? Is this actually true??

Then there’s Mycobacterium tuberculosis, which is most definitely a parasite that causes tuberculosis, yet it has a high GC content. Why?!

Writing a text book in a subject that you are not an expert in: a crazy exercise in blind stubbornness

All I can really offer of value at this stage is advice. To the current graduate students, do not make any rash decisions involving large commitments of time and effort directly following your Ph.D. defense. At this stage in your career you feel omnipotent, the world has a rosy tint, and all goals are easily attainable. It was in this state that I, a disease ecologist by training, decided to write a behavioral ecology text book.

On the surface, the project seemed like a great idea. I was a graduate student instructor for four semesters of a behavioral ecology and conservation course at University of Michigan, so was somewhat familiar with the field of behavioral ecology. There was a true need for a new behavioral ecology text integrating the study of animal behavior into the framework of life history. Further, two senior behavioral ecologists had signed on as coauthors, my job was to populate the book with parasite and invertebrate examples, and we secured a contract to write the book. So all appeared easy peasy.

Four years later, we are trudging through writing the book, and I am neck deep into my post-doctoral position. Instead of being a side author contributing minimally to each chapter with bits of knowledge from my own background, I have been tasked with writing four of the core chapters in the book, spanning Mating Effort, Mating Systems, Parental Effort, and Avoiding Enemies. While I love all of these topics, writing, and teaching, constructing chapters from scratch with no literature foundation has been a huge undertaking with many costs and not many rewards. Text books are rarely cited, and in efforts to not take time away from my current research, my unpublished dissertation chapters have remained unpublished.

So, words of wisdom. 1) Nothing is as easy as it appears on the surface. 2) Assess the immediate costs and future rewards of any given project. 3) Know your limitations. 4) Develop an ability to say no, even to people that are close to you, or senior to you, if it is not in your best interest. 5) Write text books in the twilight of your career, not the dawn.

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…

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.

Why is cancer so hard to eradicate?

Many infectious diseases can be completely cured—that is, totally eradicated from an individual—even when the parasite responsible has spread throughout the body, but when cancer has spread throughout the body, eradication is a dim hope. People often cite the similarities between cancerous and normal cells as a reason the disease is so difficult to treat, and that is certainly a problem, but I think the ecology of cancer is also fundamentally different from that of invading pathogens.

As Sandy Liebhold brought up in a recent talk, sometimes the ecology of a pest can assist in eradication efforts. Most organisms are subject to Allee effects, meaning that population growth is stunted when only small numbers of organisms are around. Animals that hunt in packs struggle to survive when there are too few organisms to form packs; sexual organisms fail to produce offspring when numbers are so low that finding mates is difficult. These Allee effects help populations on their way to extinction.

Parasites have to contend with Allee effects just like other organisms. Recent work suggests that malaria parasites have to face Allee effects in the form of early, non-specific immune measures. These immune measures appear to be overwhelmed when large numbers of parasites are injected into mice, but small numbers of parasites have a hard time of it. To use drugs to cure a patient of malaria, it is not necessary to kill every last parasite—just to kill enough parasites that immunity can mop up the rest. Cancer cells may not face the same limitations. As cells derived from the host, they are not likely to be vulnerable to non-specific immune measures. Small numbers of cancer cells might even do better, as they face less competition from other cancer cells and may fly under the radar of specific immune measures, which may tend to scale up with numbers. Therefore we may not be able to count on much help from the within-host ecology when we attempt to eradicate cancer from a person.

The situation is not hopeless—sometimes pests spread so far that eradication is deemed impractical. Aside from the economic limitations, it may be that the amount of chemical warfare required to eliminate the pest would decimate the ecosystem just as surely as the pest population would if it were allowed to grow out of control. People instead turn to monitoring the pest populations and treating so as to keep pest damage below a certain level. These ideas form the basis for adaptive therapy of cancer, which attempts to keep metastasized cancer at manageable levels instead of eradicating it altogether. Eradication may not be necessary to maintain individual patient health—managing the problem with a solid understanding of the ecology could be good enough.