Tag Archives: disease

Laveran’s eye

The military hospital of Constantine, Algeria was a fitting place to view what must have seemed the Devil in microscopic form.

Stages of the malaria parasite drawn by Alphonse Laveran

An interesting look at using skeletal remains and historical reports to reconstruct the geographic distribution of a vector-borne disease.

Contagions

England once looked very different. Much of southern Britain was marshland for most of the island’s occupied history. These bogs, fens, and marshes ensured that areas of virtual wilderness persisted  from before Roman Britain through the Norman period and beyond. Despite the difficulties of using fenlands, these areas were not only occupied throughout the Anglo-Saxon period, but important centers like Croyland, Bardney, and Ely eventually developed in the marsh.

The largest fenland region was known as ‘the Wash’.  This low-lying region drained four rivers into  a square bay of the North Sea that forms the corner between Lincolnshire and Norfolk. In Anglo-Saxon times, this tidal marsh and bog was a vast border region between the region of Lindsey and East Anglia.  Places like Croyland and Ely were islands in the wetlands.  The eighth century Life of Guthlac describes the environment of Croyland when Guthlac arrived:

There is…

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Another parasitology blog

While on the topic of host-parasite interactions, I recommend looking through an interesting science research blog, The Parasite Diary. There’s a trend in the blogosphere toward “research blogging.” While most science blogs tend to discuss scientific research in some way or another, research blogging (www.researchblogging.org) aims specifically to discuss, in detail, and without lessening analytic rigor, the results of the peer-reviewed literature in a given field. The Parasite Diary takes this approach as pertains to classic parasitology: studies examining life cycles, pathogen interactions with the host immune system, systematics–in other words, a good deal of interesting lab-based research to examine life from the parasite’s point of view.

Phylogenetic humility

Just a welcoming sentiment from Robert M. Sapolsky in his collection of science essays, Monkeyluv. Sapolsky is a professor of biology and neurology at Stanford, and his essays, often humorous, delve into neuroscience, hormones, and human behavior. Oliver Sacks has called him “one of the best scientist-writers of our time,” and while I wouldn’t put Sapolsky on the same pedestal as I do Gould, or Levi, or Thomas when it comes to prose and insight, the man certainly has his moments, which manifest in me dog-earring a corner of a page. This one stood out to me this morning on the 3 train to work while reading an essay titled ” Bugs on the Brain.” As someone who gets excited over pathogenic protozoa and animal behavior, I muttered “Toxoplasma gondii” upon seeing the heading.

Like most people who come across any mention of Toxoplasma (it gets a fair amount of press; e.g., via Carl Zimmer), Sapolsky is interested in the precision of how the protozoa can manipulate behavior. The organism relies on a simple and common two-host system to complete its life cycle: the predator-prey interaction of rodent and cat. Rodents ingest the protozoa, which encysts in the mammal, with particular affinity for denning in the brain. When rodents are consumed by felines, Toxoplasma can reproduce, new organisms are shed through feces, which happen to be a food source for rodents and thus how the life cycle comes full circle. Many pathogens that rely on multiple hosts influence behavior, and there is a bevy of literature that describes just this, particularly with tapeworms. In the case of Toxoplasma, the protozoa interferes with a rodent’s natural aversion to feline pheromones; interferes is a weak term–the organism makes the rodent attracted to feline odor, increasing the probability that it becomes successful prey.

What interests Sapolsky so about this host-parasite interaction is that a rodent infected with Toxoplasma gondii otherwise behaves normally. As he notes, infected rodents maintain their social status within the system’s hierarchy, they continue to mate and thus sense pheromones of the opposite sex, and their recognition of other vertebrate odors isn’t tampered with in the least. The protzoa is simply able to manipulate the recognition of and reaction to the pheromones of one predator, that of the definitive host. To Sapolsky (and most of us interested in the long-term interplay between parasites and their host), this is evidence of how counter-intuitive and beautiful evolutionary process can be. Sapolsky takes the opportunity to highlight Toxoplasma gondii as a correction to teleological interpretations of evolution: its processes aren’t directional, aren’t progressive.  As he notes, “We are certainly not the most evolved species around, nor the least vulnerable. Nor the cleverest.” But the punctum of his message, to borrow a term from Roland Barthes (that which “pierces” the viewer/reader), is the statement, “we need phylogenetic humility.”

Visualizing trophic interactions in an urban aquatic mesocosm

Variations in how to display the trophic interactions of an ecosystem—the food web, the regulating pressures between organisms of a particular space—have existed since the roots of the idea in community ecology. Nature—or, in particular, the relationships between organisms—has long been described as a web by many. Take, for example, the now-classic food web of Bear Island, the southernmost island of the Norwegian Svalbard archipelago, by Victor Summerhayes and Charles Elton in their seminal 1923 paper. In their illustration below, organisms are grouped into functional clusters, and arrows depict one organism being consumed by another, outlining a basis from which these systemic illustrations would build upon for decades.

Victor Summerhayes and Charles Elton's 1923 food web of Bear Island, Norway.

But this depiction of life wasn’t quite so scientifically until Charles Darwin published his On the Origin of Species in 1859, in which he wrote,

I am tempted to give one more instance showing how plants and animals remote in the scale of nature, are bound together by a web of complex relations. I shall hereafter have occasion to show that the exotic Lobelia fulgens is never visited in my garden by insects, and consequently, from its peculiar structure, never sets a seed. Nearly all our orchidaceous plants absolutely require the visits of insects to remove their pollen-masses and thus to fertilise them. I find from experiments that humblebees are almost indispensable to the fertilisation of the heartsease (Viola tricolor), for other bees do not visit this flower […] Hence we may infer as highly probable that, if the whole genus of humble-bees became extinct or very rare in England, the heartsease and red clover would become very rare, or wholly disappear. The number of humblebees in any district depends in a great measure upon the number of field mice, which destroy their combs and nests; and Col. Newman, who has long attended to the habits of humble-bees, believes that “more than two-thirds of them are thus destroyed all over England.” Now the number of mice is largely dependent, as every one knows, on the number of cats; and Col. Newman says, “Near villages and small towns I have found the nests of humblebees more numerous than elsewhere, which I attribute to the number of cats that destroy the mice.” Hence it is quite credible that the presence of a feline animal in large numbers in a district might determine, through the intervention first of mice and then of bees, the frequency of certain flowers in that district!

Darwin also described this web of complex relations as an entangled bank, “clothed with many plants of many kinds, with birds singing on the bushes, with various insects flitting about, and with worms crawling through the damp earth,” and he reflected on how each of these forms, different they may be, are dependent on one another in direct and indirect pathways while at the same time producing the kinds of ecological pressures that lead to adaptation and the rise—or elimination—of species.

A species web of a slightly different kind: Charles Darwin's 1837 sketch of an evolutionary tree.

On the Origin of Species and Darwin’s subsequent writings were foremost about natural selection, the non-random process by which biological traits become more or less common in a population. But Darwin’s idea can be, and was, applied the same to how organisms themselves become more or less common in an ecosystem—the question became the following: what are those forces and relationships that allow some species to foster in a particular environment, while others only play a minor role? Community ecologists divide these species into two initial groups: autotrophs, which produce organic matter from inorganic substance to compose the primary level of an ecosystem (the first trophic level), and the heterotrophs (1+ trophic levels), which cannot fix carbon and thus must consume organisms from the initial or subsequent trophic bases. In terms of the relationships between the autotrophs and heterotrophs, food web ecology polarizes the dynamic between which group regulates the other. In bottom-up control, also known as donor control, the autotrophs (i.e., plants and algae) produce the primary resources, thereby maintaing the nutrient availability that organisms at higher trophic levels are dependent upon. Contrasting bottom-up control is the top-down dynamic, also known as a trophic cascade, in which predation and herbivory are the factors that dominate whether a species will thrive in an environment. More typically, however, analyses in community ecology strive for some middle ground between the two.

While the organization of a food web is inherently more complex—incorporating the movement of energy and mineral nutrients; dividing the heterotrophs into carnivores, herbivores, decomposers; delineating even further between competitor species, generalist consumers, specialist predators, etc—this basic model holds steady. Because this organization is predominantly a visual one—spatial and temporal patterns and variations are a large part of community dynamics in ecological research, as outlined in a recent review by Massol et al.—an interesting aspect of studying trophic interactions lies in the possibilities for visualizing data. The first graphical interpretation of a food web was published in 1880 by Lorenzo Camerano, in a manuscript entitled “On the equilibrium of living beings by means of reciprocal destruction.” Frustrated by his time’s scientific divide over which animals are useful or beneficial to agriculture, Camerano wrote the following.

To have an exact and clear idea, I repeat, of the relations between, for example, insectivorous birds and phytophagous insects, and between these and plants, these groups cannot be studied separately. Rather it is necessary to study each in relation to all other animals to see the general laws governing the equilibrium of animal and plant species.

While Camerano’s reasoning for the paper, published in the Accademia delle Scienze di Torino, was particular and applied towards the practical, his ultimate goal in the article and its resulting visualization was of general and theoretical concern.

Plate 1, Camerano 1880. Theoretical web of plant and animal interactions.

Compare that template of trophic relationships among organism groups—including primary producers, predators, ectoparasites, endoparasites, and carnivores—with a particular illustration of an ecological community of individual species with regard to enemies of a specific phylogenetic order, Coleoptera.

Plate 2, Camerano 1880. Web of interactions between Coleoptera, enemies of Coleoptera, and ecological enemies of those enemies.

In the former, more-theoretical visualization, Camerano sides with the theory of bottom-up control—vegetation is the base layer of the trophic sphere, with interactions between higher trophic levels expanding in outward rings. In the latter, allying with top-down ideas of control, complex relations are derived not from primary production, but rather from multiple pressures of predation, forming direct and indirect influences between heterotrophs. It is the latter depiction—with its emphasis on predator–prey relationships and linear–nonlinear associations between species—that has most influenced how many visualizations of trophic dynamics are drawn. In Summerhayes and Elton’s depiction of Bear Island, the first illustration in this article, the ecologists organized the biota with priority on that relationship between predator and prey—protozoa eat the bacteria, polar bears eat seals. Even where nutrients and zooplankton entered the situation, their connection to the rest of the system was given within the framework of consumption dynamics—bacteria consume nitrogen, worms eat dead plants, algae take in mineral salts.

And nor is this choice of visualization a poor or incorrect one. However, an interesting note lies in the shift between how to organize a food web in the 19th and early 20th centuries  and what kind of information should and can be included in more sophisticated images now. When one adds in the more quantitative turn in food web analysis—such as with ecological pyramids and trophic dynamics, both of which incorporate the second law of thermodynamics to consider how energy is conserved or lost as it passes between organisms—the complexity inherent in the early food webs above exponentially increases in magnitude.

The question in producing a food web is, then, how to produce a visualization of that complexity without overwhelming our perception of reality. Sacrifice quantitative rigor, and the illustration instead appears as illusion, an over-simplification. Introduce too much information, and the traceable dissolves into surplus. Such are the balancing acts Edward Tufte outlines in his 1983 The Visual Display of Quantitative Information. In the book, the statistician argues that good information design reveals the greatest number of ideas in the shortest time, with the least ink, in the smallest amount space, akin to what Italo Calvino described as lightness in literary prose—both must, in the end, tell not only a good story, but a proper one, without sacrificing either extreme of this information equilibrium.

As some of the first illustrations of food webs came from aquatic systems, bodies of water, as simultaneously self-contained microcosms and hubs in ecological networks, are good places to look for growing trends in data visualizations. An interesting and successful  update on the classic food web comes from a paper by Kevin Caillouët et al. in a 2008 paper on enclosed aquatic communities in New Orleans, Louisiana. After Hurricane Katrina flooded 80% of the city in August of 2005, floodwater from Lake Pontchartrain to the north inundated the urban terrain for over three weeks. By completely covering most regions of the city in brackish water, flooding resulted in the production of novel aquatic habitats in lowlands, depressions, and artificial containers, to name a few. Much as a forest fire produces a blank template from which previously occupied niches can be reclaimed and monocultures overthrown, Hurricane Katrina produced a blank template from which new food webs—new trophic interactions, in new magnitudes and organizations—could be drawn. In particular, on the back of research suggesting correlations between flooding and increased mosquito populations, Caillouët et al. sought to examine how these new aquatic communities would work for or against local mosquito populations, and how this in turn could influence the human risk of mosquito-borne diseases such as that caused by West Nile virus. In particular, the team examined the quasi-contained ecosystem of abandoned swimming pools, the largest of artificial containers and one of the most prone habitats to support mosquito larval development.

Caillouët et al. sample a flooded abandoned swimming pool in the Lakeview neighborhood of New Orleans.

By sampling pools in two flooded neighborhoods of New Orleans near the 17th Street Canal levee breach, the researchers were looking at this artificial environment as a mesocosm of sorts. Unlike the simplified microcosm, a controlled, laboratory-based ecosystem used to simulate and predict the behavior of its natural counterpart, a mesocosm instead brings the natural under controlled conditions, providing a link between observational field study and the artificiality of the laboratory. These mesocosms, which were being colonized by various invertebrates, fish, and mosquito species, allowed the team to ask the following questions about the composition of these new and temporary environments: if mosquito larvae were using the pools for development; if fish moved in from Lake Pontchartrain and were able to establish populations; if predatory invertebrates migrated to and colonized pools; and, lastly, if and to what extend these latter organism groups regulated mosquito populations.  To explore how these questions translate into science, Caillouët et al. relied on a conceptual model, the first step in transforming idea into design, the prerequisite for collecting and interpreting data.

Models and interpretations of aquatic community colonization post-Hurricane Katrina. Caillouët et al. 2008.

The conceptual model (A) of Caillouët et al. is not all too different, as a theoretical insight, from the initial plate by Camerano in 1880. Just as Camerano endeavored to clearly illustrate the relationships that draw together insectivorous birds and phytophagous insects, and between these and plants, the modern model food web illustrates the general relations between four main groups of organisms: the top predators, the specialist predators, the competitor species, and the prey. Much as Summerhayes and Elton used arrows in their 1923 depiction of an aquatic food web to illustrate the direction of the relationship between two or more organisms, the above model demonstrates a direct (and negative) effect of one group on another with solid lines, while dotted lines indicate an indirect (and therefore positive) effect. Continue reading

Metaphor of microglia: the maintenance amoeba of the brain’s neural network

[Here on out, eukaryography will have weekly or so examples and discussions of creative metaphors used by writers of scientific phenomena. Today’s imagery comes from Mo Costandi at Neurophilosophy]

It is said that the human brain contains roughly 10 billion neurons, each of which is connected to those other neurons through 10,000 synapses. This figure, massive as it may be, is also an understatement—Mo Costandi at The Guardian notes that in actuality the numbers come in closer at hundreds of billions of neurons and glial cells, those non-neuron cells—also known as neuroglia—that maintain homeostasis in the brain and provide support and protection of neurons. In turn, this quantity of cells produces more like  a quadrillion synapses.

To maintain some control over this complex information processing system, our brain generates more neurons and neuroglia than necessary, ensuring a surplus of connections. To reduce noise in this system, the brain relies on a process known as pruning. Also known as neuro-structural reassembly, pruning can occur through several interrelated scenarios. In one, the brain must replace simpler associations with a matured understanding of complex relationships—as we mature from childhood, our brain does as well, and needs reconsideration of the economy of neurons to do so. This process is part of the more general act of the network’s housekeeping. Neurons that have been damaged, are decaying, or are no longer necessary are removed to improve the overall functioning of the organ. Costandi writes that although neuroscience has know this process continues into and somewhat through our adult lives, the field has been in the dark in regards to the mechanisms—the how of X connecting to Y—of pruning. Costandi reports that now, a team of Italian researchers has been able to clarify this void in our understanding. Pruning, they have found, occurs through the actions of cells called microglia, which scour the developing human brain and engulf unnecessary synapses.

Microglial cell from the mouse brain expressing green fluorescent protein. Photograph by EMBL/ Rosa Paolicelli.

The microglia are related to the macrophages of the innate immune system, and functionally are very much the same. A variety of macrophages exist,  and their roles include ingesting foreign material, releasing cytokines to stimulate other macrophages, and presenting antigens. In the same way, microglia act as the initial defense against invading pathogens and substances and performing maintenance tasks. But Costandi doesn’t limit his definition of microglia to the vocabulary of immunology—he also draws on a personal favorite, that of protozoology. Microglia, he writes,

crawl, amoeba-like, through the spaces between neurons, using their protrusions to detect viruses and microbes that have infiltrated the brain and quickly engulf those they find.

Amoeba, members of the genus Amoeba, were discovered by early cell biology in 1757 by  entomologist August Johann Rösel von Rosenhof. In his Insecten-Belustigung (Recreation among the Insects),  Rösel described, sketched, and discovered that one species of these organisms, which he called “the little Proteus,” when touched, drew its octopus-like figure together.

Engraved colored figures of Volvox and amoeba, August Johann Rösel von Rosenhof (1757).

This form-changing ability, which became the characteristic of amoeba that gave the group its 18th century name, Proteus animalcule—after the Greek god Proteus, who could shift his shape—is an aspect that allows these organisms to feed. Amoeba have cytoplasmic extensions called pseudopodia that accout for this shape shifting–like imagery. This process is the prerequisite for phagocytosis, the act of engulfing other organisms or matter in the pseudopodia and bringing them into the amoeba’s body to be metabolized. This “cell eating” phenomenon is also exibited by the macrophages and microglia that Costandi notes in his article:

Phagocytosis means “cell-eating” and is the process by which microglia and other cells take up solid materials. First, the material is pulled towards the cell membrane, which then begins to invaginate, or fold in on itself, to envelop the material. As the in-folding continues, the outer edges of the membrane are drawn together until they eventually meet, producing a globule (the vesicle), which then buds off and moves into the cell. The contents of the vesicle are then processed appropriately—microbes are destroyed and membrane proteins and other cellular components recycled.

Below, an amoeba, Vannella sp., engulfs an unspecified cell through this meticulously described process.

And returning to the first part of the metaphor, that of the microglia-as-macrophage, in the following video a white blood cell chases bacteria through a maze of erythrocytes.

Through the experiment performed by Rosa Paolicelli et al.the details and methods of which are explained in full by Costandi at his Neurophilosophy blogmicroglia in the brain tissue of mice were found to be engulfing, in much the same way as an amoeba or macrophage, fragments of a protein known as PSD-95, which is major part of the protein network found in active synapses of the brain. In the following video from Nimmerjahn et al. (2005), we can visualize microglial cells patrolling synapses for functional deficits.

Therefore, Costandi writes, “the developing brain treats unwanted synapses as if they were unwanted invaders. It dispatches microglial cells to survey the state of synapses in their surroundings and to dispose of the ones that are wired incorrectly or superfluous.” To the microglia in our neural network, unnecessary and outdated synapses are akin to pathogens in the bloodstream, particles of algae to a grazing amoeba in a drop of lake water in Rösel’s German countryside.

The painted lives of ciliates and schistosomes

Art has always been one way to mediate tensions, tensions such as those between the logic-driven mind of scientific inquiry and the subjective experience of the non-human, what Jakob  von Uexküll called an organism’s umwelt. Thomas Nagel famously argued that we can never know what it is like to be a bat, or any non-human organism, but whether through experimental-minded writings on what the world might be through a tortoise’s point of view  or through watercolor paintings, the artistic hopes to bridge various umwelten more so than a declaration of scientific understanding—the difference lies within the distinction of this is how a starling sees the spectrum of light and thus the world (science) and this is how a starling might see the world (art). Might opens possibilities, a window into creative endeavor.

The paintings of Emilie Clark might be one answer to Nagel. Clark, a painter based on Brooklyn, NY, has worked on a series of projects involved in life on a microscopic scale. In a 2004 gallery showingPondering the Marvelous, Clark responds to the writings of Mary Ward, a 19th-century Irish natural historian and painter, specifically Ward’s A World of Wonders Revealed by the Microscope. In imagining Ward’s writings as personal letters to the artist, Clark produced two series of her own watercolors—the first based on Ward’s description of Ireland’s microscopic landscape, and the second on Clark’s own collection.

Untitled MW-#50. Painting by and courtesy of Emilie Clark.

Untitled MW-#12. Painting by and courtesy of Emilie Clark.

The paintings are not meant in their entirety to be illustrations of these organisms’ umwelten, and nor do they achieve this ideal. But these paintings play with the possibility of “what if?” And it is this play that creates an opening in our imagining of the umwelt of other species. Perhaps best said by the poet–immunologist Miroslav Holub, the act of play allows us, simply, to “avoid the aridities of rationalism.” Yet this is not Clark’s first foray into toying with the lifeworld of other microorganisms.

In a previous post, I briefly touched on the topic of cover art for scientific journals—in this case, a watercolor of a stag beetle by Albrecht Dürer for a 2005 issue of Emerging Infectious Diseases. One of Emilie Clark’s projects, which one can find on her webpage, is likewise producing watercolor medical illustrations, many of which have found their way onto the covers of The Journal of Experimental Medicine. The JEM, since its beginnings in 1896, publishes original research on the physiological, pathological, and molecular mechanisms that are encountered by or reactions of the host in response to disease. In the case of a November 2005 issue of the journal, the target pathogenic organism of Clark’s illustration was Schistosoma mansoni, one of three causative agents of human schistosomiasis.

From the cover caption of JEM 2005; 202 (10). Emilie Clark's watercolor of S. mansoni eggs. The eggs secrete a chemokine binding protein, thereby suppressing the inflammatory response.

Schistosomes are blood flukes (trematodes) that belong to the genus Schistosoma. In addition to S. mansoni, the other two members of this genus that cause disease in humans are S. hematobium and S. japonicum. The disease itself, caused by human contact with water home to schistosome cercaria, is a definitive chronic condition whereby the mature schistosomes, after reaching the final stage of their life cycle, migrate to the mesenteric or rectal veins and begin to mate, thereby producing up to 300 eggs per day for the rest of their reproductive lives—which can be as long as 4–20 years. A proportion of these eggs will become lodged in the target veins, where they mature and secrete antigens that elicit an intense immune response in the host. It is this immunological reaction, which can continue as long as the mating worms and the eggs continue to exist in the body, that characterizes schistosomiasis. It was the point of the primary research communication by Philip Smith et al., the inspiration for the choice of Clark’s watercolor, to demonstrate one way in which S. mansoni modifies the human host to tolerate decades-long chronic infection without causing death. In particular, the researchers demonstrated that S. mansoni eggs secrete a protein into host tissues that binds certain chemokines—proteins that induce directed chemotaxis, how certain cells direct their movements according to particular chemicals in their environment, in nearby responsive cells—and inhibits their interaction with host chemokine receptors and their biological activity.

Now, compare Clark’s interpretation of the organisms and this phenomenon with a direct realistic representation through a microscope. Continue reading