Thursday, January 24, 2019

An excerpt from PIECES OF THE PLAINS, regarding undergraduate research in parasitology

I’d like to tell you a story about The Firm, but without passing judgment on any of the people, the behaviors, the relationships, or the outcomes involved. What follows is absolutely true, from what I ordered for dinner one evening to what I was doing a few years later at my computer on a morning in April, 2009. The student’s name is also true: Shay Hampton; she worked as an undergraduate researcher in my laboratory for a couple of years before graduating in May, 2009. In this regard, she is no different from many others. There has been a long parade of students, both undergraduate and graduate, through our laboratory, and most of them have gone on to very interesting lives. Shay also is good one to talk about in some detail because she exemplifies the human resources that walk into every American university’s front door annually by the thousands. In addition, she illustrates the main lesson of research: the allegorical journey that has no direct bearing whatsoever on global human affairs but has every kind of bearing on our intellects, on the traits that drive our global human affairs.
Although she doesn’t know it, and wasn’t there, Shay’s story begins at the Outback Steakhouse in Lincoln, Nebraska, several years ago. Karen and I were seated in a booth, one of those to the left of the bar as you walk in. She ordered a glass of Pinot Grigio and shrimp; I ordered Jack Daniels on the rocks and salmon. We were having a nice conversation, mostly me listening to whatever happened during her day at work, when four suits came in and sat in the booth behind me. There were three good-looking young-ish men and one good looking young-ish woman, all dressed nicely, obviously out-of-town professionals unwinding after an intense day doing something serious. They ordered drinks and proceeded to start talking about the University of Nebraska’s Board of Regents. Naturally, I began to listen, and Karen also grew quiet, listening, now watching this group over my shoulder. 
From being employed by the University of Nebraska for decades, and being involved in a variety of university assignments, I knew several of the governing board members on a first name basis. One of them had been my dentist, usually stuffing my mouth full of cotton and clamps before asking how “things were going down at the University.” I was still sipping my Jack Daniels when the familiar names started drifting from the suits’ booth over into ours. One by one, members of the Board of Regents were being analyzed: their financial situation, their business connections, their voting records on various issues, whether they were conservative (most always are, sometimes seriously so), or liberal (few are, ever), where they lived, and most interestingly, what it would take to talk them into voting on an agenda item to be considered the next day: exclusive vending rights, including all University of Nebraska facilities statewide, at all campuses, and in all athletic venues. The four suits were from Pepsi Cola. History shows they handled the Board of Regents well and won the contract. You cannot buy Coca Cola products on our campus now, so like all other employees who so desire, I bring my own to school. But I will never forget that evening at Outback. Now fast forward a few years to the student named Shay Hampton.
In one of the more far-sighted actions my institution has carried out over the four-plus decades of my employment there, someone in the upper administration squeezed money out of Pepsi to support undergraduate research as part of the exclusive vending rights deal. The program is officially called UCARE (Undergraduate Creative and Research Experience), and through brief proposals, UNL students can apply for small grants to support their independent study under a faculty member’s tutelage. Thus Shay joined a small group of undergraduates working in my lab, taking advantage of Pepsi’s “generosity.” When student research is involved, especially undergraduate research, I always try to match personalities and material. Shay was not much different from other undergrads in the sense that she had many obligations, some of them conflicting, and all of them functioning to make time management her daily challenge. Nor was she different from our other undergraduate researchers in another respect: her project was to concern the biology of gregarines, obscure one-celled organisms that live mainly in the gut of insects and other invertebrates. 
We talked about various projects that might be done with these parasites. Many years ago, when it became obvious that undergraduates wanting to do research were to become a regular part of my professional life, I asked the question: how can undergraduates accomplish a true scientific exploration, given the demands on their lives, the time constraints, and the issue of money? The key to mentoring success in this case is possession; the student, not the prof, has to own his or her project. What are the easiest, most economical, legitimate research projects for a twenty-year old student to actually own? What can a college junior do in the next two years that accomplishes the same thing a faculty member has to do in those same two years: publish an original paper, a contribution to what’s called “the primary literature”? And finally, what question can this junior in college address that demands he or she take on all the logistical burdens of research that comes along with ownership—everything from washing glassware to maintaining cultures to statistical analysis? Many years ago I answered those questions in the most effective and economical way I could imagine: work on the most common, most diverse, most cooperative, and most beautiful of all parasites, the gregarines.
Let’s begin with personality. Shay Hampton appeared on the roster of my Field Parasitology class, BIOS 487, during the summer between her freshman and sophomore year, at the Cedar Point Biological Station (CPBS) north of Ogallala, Nebraska. To quote from the several hundred letters of recommendation I’ve written for former CPBS students: “Field Parasitology at CPBS is a very demanding course that requires laboratory and field exercises, a collection, daily exams, daily written assignments, an independent research project, and regular oral and written presentations. In addition, CPBS is an in-residence program, so we do get to know the students very well and watch them interact with their fellow students.” Shay’s appearance in this class was unusual, especially without being personally recruited by me because of previous classroom performance. She’d obviously made a decision to stretch out, intellectually, and seek a challenge not many of her cohorts would welcome. She’d also obviously acted counter to advice commonly dished out by professional advisers, who typically tell students to “wait until you’re ready for this challenge,” whatever “ready” means to people like professional advisers who have never been to a field program. Her appearance in Cedar Point’s Goodall Lodge on the Sunday evening prior to the start of classes is thus a key to her personality: she’s not afraid of much. In fact, after watching her work for two years, I’d say she’s probably not afraid of anything.
At Cedar Point, Shay jumped on a class project involving gregarine parasites of damselflies. I say “jumped on” because the first day of class we’d done an exercise with these parasites as an excuse to learn entomology, dissection and measurement techniques, identification (both of the parasites and their insect hosts), spreadsheet design, data analysis, and presentation, all in the space of fourteen hours. Shay and her partner, Kacie Meyers, another fearless first-year student, immediately picked up on a number of interesting questions that could be addressed using the numerical information provided by this host-parasite system. Where most students saw something they needed to learn, Shay and her partner saw something that gave them the power to conduct a formal inquiry, something to do, which in the doing would give them transferable skills. Three weeks later Shay and Kacie stood up in front of the class to present their results and data interpretation, conceding, in the process, that we were pretending to hold a real scientific society meeting by role-playing. They’d worked hard on their PowerPoint images, the sequence of statements and ideas, the rationale behind their project, the hypotheses to be tested, the methods, the data, and finally, their conclusions about what it all meant. Now it was time to put on a show, and they knew it.
Was Shay a “real” scientist after only three weeks in the field? I answer the question “yes,” although many, if not most, of my colleagues would claim “no.” Why the difference of opinion? My answer to this question is: when a sequence of mental acts characterizes your approach to a problem, no matter how seemingly trivial that problem, then you have become defined by the discipline. When you begin thinking like an historian then you’ve stepped over the line that separates historians from non-historians, perhaps not very far over the line, but over, nevertheless. The same statement can be made about the line between artists and non-artists, musicians and non-musicians, and scientists and non-scientists. Once this mental transformation occurs, the rest is easy. Why might my colleagues deny such assertions? I don’t know the answer to that question, but I do know that the Shay Hamptons of the world tend to walk into my lab and not theirs, as the real Shay Hampton did a few weeks after her summer’s Cedar Point experience.
I was sitting at my microscope doing some biology; I don’t know exactly what kind of biology, but most of mine involves microscopes (see chapter 4, “Through a Lens”). Shay came in, sat down at the table across from me, and said:
“May I work in your lab?”
Usually when I get asked such questions, by such students, I try to remain relatively calm and professorly rather than jump up and down screaming “YES!!” That simple question—May I work in your lab?—is the ultimate reward of a scientist. Nor do I remember why we settled on the particular insects she decided to study for the next two years, except that we had these two beetle species growing in culture, and no one had looked at their parasites, at least not with a great deal of care. Unexplored territory is a powerful lure, and not just for the Roy Chapman Andrews’ of the world; college sophomores like Shay also tend to be fascinated with the unknown, even if the wilderness is inside an insect instead of out on the Gobi Desert. Furthermore, the beetles we were rearing—Cryptolestes pusillus and Latheticus oryzae—are notorious stored products pests. There is an outside chance you’ve eaten some of these insects, or their parts, because they infest flour, cereals, and grains around the world, and cereal grain products, especially if stored for any length of time, are rarely free of insects and mites. The beetles’ scientific names reflect their physical stature and secret lives: “crypto-” means “hidden,” “pusillus” means “very small,” and “oryzae” refers to rice. If crawling upon a dime, one adult Cryptolestes pusillus could sit easily on the tip of Franklin Roosevelt’s nose and an adult Latheticus oryzae could fit in his ear with plenty of room to spare.
The ultimate problem with hosts and parasites is a co-evolutionary one, an explanation of why certain parasites occur in certain hosts. This problem is found throughout areas such as human and veterinary medicine, disease ecology, global movement of pathogens, diagnosis and diagnostic techniques, immunology and vaccine development, and budgetary planning for disease control. The terms “swine flu” and “bird flu,” for example, reveal the movement of infectious agents into places—a human’s respiratory system, for example—where they did not originally evolve.
Shay’s project thus was a small model of a very large phenomenon. Her material came in the form of two small plastic jars containing whole wheat flour, wheat germ, wheat bran, and yeast, all in magic proportions, and . . . beetles living happily and reproducing like crazy. Each jar was a simple model for an economy with a public health problem: organisms, most of which were infected, seeking and finding nutritional needs, perhaps competing with one another for mates, reproducing, and eventually dying. In the lab, C. pusillus and L. oryzae (whose Latin names are certainly no odder than names in the Lincoln, NE, telephone book!) were separated, but in nature they could, and probably should, occur together. So Shay’s simple question became: do these stored grain pests share parasite species, and if not, why not? But before she could do anything else with the parasites in these insects, she still had to answer biology’s most pervasive and enduring question: What is it? 
This question, of course, refers to the beetles’ parasites. If you can’t distinguish letter X from letter Y, then you don’t know whether they occur in the same word. If you can’t distinguish Parasite A from Parasite B, then you can never answer fundamental questions such as: are they restricted to their respective host species or can they invade other host species? The problem of cross-infection is a fairly important one, and not just for influenza virus. For example, a roundworm named Baylisascaris procyonis, that occurs naturally in raccoons, can invade humans, especially young children, and end up in the nervous system, causing severe meningoencephalitis and subsequent neurological disorders. Cats, including family pets, can harbor Toxoplasma gondii, a protozoan capable of invading fetal nervous systems, resulting in tragic and fatal hydrocephaly in newborn infants. And the last time you went to the blood bank as a donor, you were asked whether you had Chagas’ disease, caused by a notorious zoonotic parasite, a flagellate sustained largely in wild mammals throughout much of Latin America but that easily infects humans who are bitten by the carriers, which are large blood-sucking insects (“kissing bugs”). 
So Shay decided to ask this same question about her model system consisting of two tiny beetle species: can their parasites infect the opposite hosts, and if not, why not? But first, as always in unexplored regions, whether they are the Gobi Desert or insect intestines, we must solve the problem of what we’ve actually discovered. In Shay’s case, the discovery was of two kinds of truly beautiful and mysterious cell-organisms, both unknown to science. She was thus faced with a task that has challenged all biological explorers from Aristotle, Linnaeus, and Darwin to modern explorers, deep in tropical jungles trying to discover exactly what it is we Third Millennium humans are destroying at a mass-extinction rate. This task is, on the surface, a simple one: describe what you’ve found. But in practice the task is anything but simple. Indeed, the description of an hitherto unknown species is one of the most highly educational of all biologists’ options, primarily because the word “description” is a technical one, meaning a published paper that fulfills stringent criteria of measurement, illustration, and justification, and also passes anonymous peer review.
After two years of measurement, making permanent slides, analyzing digital images, collecting beetles feces for cysts, experimenting with methods for ensuring cysts actually developed into “spores” whose structure she needed for her formal description, digging into the depths of ancient and arcane literature, much of it in foreign languages, studying the electron microscope screen for the perfect images, and talking constantly with her lab mates about the criteria for distinguishing species, Shay finally pulled a piece of antique equipment from a drawer and attached it to a microscope. This equipment was a camera lucida, a device that splits a light beam and allows you to trace an image with your pencil, even though that image is of a structurally complex cell 1/3000 of an inch long. Wikipedia’s contributor on the subject claims “The camera lucida is still available today through art-supply channels, but is not well-known or widely used.” In this case Wikipedia’s authors are right on target: camera lucidas are often considered antiques, and some of the ones in our lab certainly are. But they are essential instruments for describing nature because they allow a person to draw pictures that have the correct proportions. Those pictures, with structural details you cannot capture with a photograph, are essential features of any new species description. 
Thus Shay learned the pleasures of working with a camera lucida, the challenge of making large-scale ink drawings, and the satisfaction of arranging those drawings into a plate worthy of publication. Then to fulfill her obligations to Pepsi, she took all the information from her two years worth of labor: all the methods, hundreds of measurements, data and statistical analysis, digital photomicrographs, electron micrographs, others’ published descriptions (often decades old and in obscure journals), information about the beetles, rationale for doing the project, and conclusions, and made a poster for presentation at a scientific meeting. “Made a poster” is code for “now, instead of a scientist, you’re a marketing and PR person.” Shay Hampton’s intellectual journey may have started with the most pervasive and enduring question in biology—What is it?—but as is the case with all scientists, her journey ended with a writer’s and artist’s dilemma: tell a true story, to a public that knows nothing, and probably cares nothing, about your subject, through the use of skillfully, and thoughtfully, assembled words and pictures, and tell that story in a way that makes the public understand, and appreciate, what you’ve accomplished. 
Shay Hampton’s poster is now tacked to the wall across from my laboratory door. Every day I look at it and am reminded of The Firm’s essential lesson: years of intellectual endeavor end with a seemingly minor accomplishment that can be buried in an obscure journal or summarized on a 30” x 48” sheet of slick-finished paper. But the real product of this endeavor walks away to a summer job, carrying the experience in her brain. The reputation mongers look at Shay’s poster and think: hmmm, just another species description. Why hasn’t she cured cancer? The answer to that last questions is: well some day she might; but for the moment, she’s a walking, talking, example of The Firm’s raison d’etre: that allegorical journey during which one develops a deep appreciation for the fundamental nature of inquiry. And even though she was an undergraduate, her basic experience is the same as that lived by every scholar, including every faculty member, no matter the discipline, no matter how much money is involved, or how much technology, who embarks on that allegorical journey.