SickPapes Special on Suren N. Sehgal (1932-2003) and the discovery of the TOR pathway
Vézina, C., Kudelski, A., Sehgal, S.N., 1975. Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J. Antibiot. 28, 721–726.
Laplante, M., Sabatini, D.M., 2012. mTOR signaling in growth control and disease. Cell 149, 274–293.
In our younger and more vulnerable years, it was exciting to learn “how things work.” But, as we’ve grown older, and gotten more seriously into smoking weed, it is the discovery stories behind ”how things work” - the ways that people figured it out in the first place - that we find truly spine-tingling. We’ve said it before, and we’ll say it again: there is nothing better than choosing a hot-ass research topic, strapping yourself in, and doing a psychadelic literature search all the way back to the beginning to see how it all got started. The euphoria from the resulting “PubMed High” is, truly, nature’s candy.
Case in point: TOR signaling. TOR signaling is a highly conserved pathway that cells use to respond to nutrients and other external signals, and is therefore a central focus for tons of important biomedical research on conditions that involve cell growth and/or nutrition, things like cancer, diabetes, and obesity. There are, quite literally, shit-loads of papes about TOR - trust me, I’ve smoked them all.
Given how “mainstream” and “biomedical” this field is, I was not at all emotionally prepared to learn how the pathway was discovered. To begin, look no further than the name of the pathway: TOR, which stands for “Target of rapamycin.” This name refers to the fact that the pathway responds to (i.e. is disrupted by) a drug called “rapamycin.” Rapamycin, it turns out, is where the story gets freaky-deaky, and leads us to the trippiest place on earth, Easter Island. And Easter Island, as we know, is where all scientific discoveries ultimately begin.
In 1964, a team of Canadian microbiologists went to Easter Island, looking for soil microbes that produce natural antibiotics. One of the soil samples they collected contained a bacterial strain which secreted a factor with potent anti-fungal activity. Dr. Suren N. Sehgal and his team named this factor rapamycin, in honor of the local name for Easter Island, Rapa Nui.
There is a cliche of scientific discovery stories that goes like this: an unsuspecting biologist, studying some relatively obscure organism, winds up identifying a molecule that has wildly important and far-ranging applications. Penicillin is the most famous example, but similar stories are told about Green Fluorescent Protein (from jellyfish; now used to visualize proteins in vivo), thermostable Taq polymerase (from a hot-springs bacteria; now used to amplify DNA), and CRISPR-associated enzymes (from yogurt bacteria, now used to achieve GATTACA-esque dystopic fantasies about modifying babies).
Of course, by now it has also become almost cliche to point out that this Surprise-turn-NobelPrize narrative is total bullshit, and all of these discoveries were in fact made by excellent, forward-thinking scientists who knew what they were doing. Not to say that there wasn’t some element of serendipity in how revolutionary such discoveries ultimately became, but it’s important to emphasize that these discoveries were not lucky one-offs. As many mythbusters have pointed out, even the “accidental” discovery of Penicillin was actually done by a guy who had devoted his whole career to identifying anti-bacterial compounds, and involved lots of work by others who are rarely credited. As it has been written before: “Tenacity frequently precedes rather than follows serendity.”
Point is: Dr. Sehgal did not just “get lucky.” While it might be tempting to imagine him as an esoteric microbiologist with no idea how important rapamycin would become, this was not how it went down at all. Dr. Sehgal ran a lab at a pharmaceutical company that was set up specifically to systematically screen for anti-microbial factors produced by other microbes. Once they identified these Easter Island bacteria, they quickly isolated the active compound (rapamycin), figured out how to produce it in quantity, and then discovered that, in addition to it’s anti-fungal properties, rapamycin worked in mammals as a powerful immunosuppressant. (Rapamycin was eventually turned into a drug to help suppress the immune system after organ transplants.) Rapamycin was soon discovered to also suppress the proliferation of some kinds of tumors.
In the 50 years since the discovery of rapamycin, an enormous number of researchers have worked to identify the pathway that is targeted by rapamycin (the TOR pathway), and have begun to figure out the complex ways that this this pathway links external signals (like nutrition) to control of the cell cycle and other basic metabolic processes. This explains how rapamycin suppresses tumor growth (by blocking the progression of the cell cycle), and it suppresses the immune system (by blocking the proliferation of immune cells in response to antigens). That’s what we call a “hot pathway.”
To read more about Suren N. Sehgal, check out this moving tribute to his research and life, which celebrates “his life and his contributions to mankind.”
Natural history-driven, plant-mediated RNAi-based study reveals CYP6B46’s role in a nicotine-mediated antipredator herbivore defense.
Kumar P, Pandit SS, Steppuhn A, & Baldwin IT (2014).
PNAS, 111 (4), 1245-52 PMID: 24379363
Today, Sick Papes is thrilled to sit down with Dr. Ian Baldwin, eminent biologist and pioneer plant whisperer, to discuss a recent pape from his lab about the ineffable love/hate triangle between feisty tobacco plants, lazy grazing hornworms, and hungry-as-hell spiders. Dr. Baldwin is a Director at the Max Planck Institute for Chemical Ecology in Jena, Germany, where his group heroically uses genomic and molecular tools to study plant and animal interactions in the real godforsaken desert. We would also like to congratulate Dr. Baldwin on his recent election to the National Academy of Sciences (!), and remind him that there is no rule in the Academy charter that prohibits nomination of nebulous blog frats.
SP: Dr. Baldwin, your pape uses an incredible combination of plant genetics and insect physiology to study the interactions between tobacco plants, moth larvae (hornworms), and predatory spiders. You find that wolf spiders avoid eating larvae that exhale nicotine acquired from their favorite foodstuff, tobacco. It all fits together like a delicious stew. Were these experiments done entirely in the field, or did you have to bring moths and spiders back into the lab? How many field seasons did it take your group to pull all this off?
IB: Stew it was indeed, requiring about equimolar amounts of field and lab work. The field work started way back in 2009, when Anke Steppuhn and I used irPMT plants to figure out if M. sexta larvae were co-opting their host plant’s nicotine for their own defense against attack from Geocorus bug predators, and they were not…It was not until Sagar Pandit and Pavan Kumar discovered the spider in night surveys of infested irPMT plants that this project started to make sense. Then it was very fortunate that the spider turned out to be well behaved in the laboratory, providing the sorts of bioassays that we show in the videos that are part of the paper.
SP: You often work at a field station way out in the Utah desert that is operated by Brigham Young University. How did you end up working there? Does desert field research attract Edward Abbey types who are predisposed to hunkering down in the wilderness and writing screeds against anthropocentrism? Are you interested in reading my manifesto?
IB: It’s a long story, some of the details of which are in a feature article that Allison Abbot wrote in Nature a few years back, but here I just want to mention how fortunate we all feel to be able to work at the Lytle Ranch Preserve. While many universities are investing millions into building new laboratory buildings to further research, BYU is the only one that I know of that has realized that their nature preserve at the Lytle Ranch Preserve is an invaluable laboratory for the study of gene function. Genes function in organisms in the habitats that they evolved in, and if we really want to understand gene function, then we need to manipulate the expression of genes in organisms dealing with the rough and tumble of nature.
But to your second question, the field work is a special time for me and the students in the group. We get to work very intensively together under the intimate circumstances of field life, and we learn how to really “phytomorphize” ourselves, so that we can see the world as a plant would, and better anticipate how it’s solving the challenges that are thrown at it.
SP: In your pape, you use RNA-interference in tobacco plants to silence a gene in moth larvae that feed on tobacco leaves. You show that it clearly works, but do you understand how? How did you figure this out? Would this strategy work to silence genes in any insect?
IB: The PmRNAi procedure is one that we have published on prior to this work (see the Kumar et al. 2012 PlosOne paper in the refs), and we know some of the constraints (length of DS fragment, the role of plant Dicers), but we are a long way from understanding how the procedure works in detail. We are trying PmRNAi to silence genes in all of the heterotrophs that feed on our plant: insects of different feeding guilds, genes in the predators that feed on the insects that feed on the plant, and mycorrhizal fungi. One day we will try to silence genes in rabbits….
SP: There is one point in the pape when you sit back and admit that your investigation “stumbled”, when you did not find enough nicotine metabolites in larvae or their frass (larval poop) to account for all that the nicotine they ingested. It is only after observing spider predation behavior that you realize that the hornworms might be “exhaling” nicotine through their spiracles. Was this actually the order in which events occurred? Do you ever impose narrative structure onto a pape, or do you prefer to describe the process of discovery as it happened?
IB: The discovery process is always a narrative process, one that is continually revised by new data, but it really was the spider that showed us the way in this project. It took a while for us to realize that what was happening when the spiders were palpitating the nicotine-replete larvae and rejecting them, but this was the defining moment for this project. When Pavan figured out how to glue PDMS tubes to caterpillar spiracles and could show that the caterpillar’s exhalations were full of nicotine in normal caterpillars but depleted in CYP-silenced caterpillars, then everything fell into place. But without the spider, we never would have thought about caterpillar breath.
SP: One major finding of the pape is that a gene called CYP6B46 is somehow important for transporting ingested nicotine from the larvae’s gut to the hemolymph (insect blood). Without nicotine in the hemolymph, the larvae fail to exhale nicotine and are unable to deter predatory spiders. How did you initially figure out that this gene is required for normal nicotine transport? Do you think this is somehow key to the hornworm’s enviable nicotine tolerance?
This was a gene that was strongly regulated by nicotine ingestion, something that we had published in an earlier study (see Govind et al. 2010 PlosOne in the references). When we finally got the PmRNAi procedures working, we could finally start to figure out how this gene was involved in processing ingested nicotine.
SP: In 1983, you published a landmark pape that showed that trees responded to chemical signals released by their neighbors. Was this something that you set out to test directly, or a result you stumbled into? In other words, had the possibility of plant communication been considered previously, or was it an entirely novel concept at the time? I guess what I’m trying to ask is: did you have a hallucinogen-induced vision of screaming plants?
IB: Nothing nearly as dramatic. I was an undergraduate at the time and my mentor at Dartmouth College, Jack Schultz, suggested that if I wanted to pursue graduate work in plant-herbivore interactions, I should visit the labs of all the stars in the field. I had a job to transport a BMW motorcycle from the east coast to the west coast, and used the opportunity to criss-cross the country on the motorcycle visiting labs and the last on the list was that of Davey Rhoades, at the University of Washington (he was a senior scientist in Gordon Orians’ lab). And Davey had just finished a set of field experiments that involved moving caterpillars between alder trees, and one interpretation of the data was that trees were somehow communicating with each other via volatile emissions. I knew that I could design a much cleaner experiment to test the “talking tree” hypothesis and as soon as I got back to Dartmouth from that motorcycle trip, I designed and conducted the experiment that was published in Science. So it was Davey Rhoades who was the visionary in this field.
SP: Much of your work illustrates how animals use chemical signals to communicate with each other, as well as other species. Do you think such interactions require central integration of sensory signals? Do you consider the analogy with animal neurons (“plant neurobiology”) apt or useful?
IB: Chemical signaling predates multicellularity so central integration is not necessary for sophisticated behavior to evolve in response to chemical signaling. The metaphor of plant neurobiology is becoming more apt as more discoveries about the signaling function of plant electrical response are being uncovered. Edward Farmer’s group at Lausanne are providing the first evidence of the filtering of these electrical signals (in the activation of jasmonate signaling in distal plant parts), so it may well turn out to be a metaphor more apt than previously thought.
SP: My favorite sentence in your pape is:
“All organisms in their natural environments, and particularly plants, as they lie at the base of all terrestrial food chains, are carefully scrutinized by literally thousands of other organisms with very different, frequently highly hostplant-tuned sensory modalities; the phenotyping services that competitors, pathogens, herbivores, pollinators, predators, and the plethora of different types of mutualists that interact with an organism lacking the expression of a particular gene, allow for an unbiased “ask the ecosystem” approach for the discovery of the function of this gene at an organismic level.”
Putting genetic phenotyping aside for a moment, have you ever applied this “ask the ecosystem” approach to other questions in your life?
The modus operandi in my group is first to “ask the organism” an interpretable question, and then to silence the genes that are part of the organism’s transcriptional answer. With these gene-silenced organisms, we then “ask the ecosystem” for answers as to what this organism was trying to do. For a large fraction of the plant genes that we silence, the plants show no phenotype when we grow them in the glasshouse, but when we transplant these gene-silenced plants back into their native habitat, the ecosystem very frequently tells us the function of the plant gene. So yes, we do this all the time.
Seyfarth EA (2006). Julius Bernstein (1839-1917): pioneer neurobiologist and biophysicist. Biological cybernetics, 94 (1), 2-8 PMID: 16341542
We at Sick Papes do not operate under the illusion that we are only the folks that love a dank ‘ticle. But it’s rare to find a practicing researcher who also takes the time to investigate the important historical exploits of his/her field. Throughout his career, Ernst-August Seyfarth has done just that, authoring several papes about relatively obscure hero neurobiologists such as Ludwig Mauthner (1840-1894), who discovered the infamous Mauthner cell, Julia B. Platt (1857-1935), one of the first comparative neuro-embryologists, Tilly Edinger (1897-1967), an early paleoneurologist, and Johann Flögel (1834-1918), one of the first insect neuroanatomists. At the same time, Dr. Seyfarth sustained a thriving research program studying mechanosensation in spider slit sensilla, as well as spider behavior (at one point, investigating the origin of spider push-ups).
My favorite of Seyfarth’s historical narratives is the story of Julius Bernstein, a bad-ass German physiologist who was the first to describe the action potential (despite this noteworthy achievement, I had never heard of the guy). Bernstein was born in Berlin, where, after completing medical school, he returned to do a post-doc with the perpetually belligerent Hermann von Helmholtz, a pioneer of physics, physiology, philosophy, and competitive lifelong moustache consistency. While trying to best his boss with a blend of buffed bald-head/bushy beard, Bernstein developed a brilliant contraption called a differential rheotome, or “time slicer”.
The rheotome (shown above) was a sort of “ballistic galvanometer” that consisted of a turntable that opened and closed two circuits as it rotated. One circuit transiently stimulated the nerve, and the other instantaneously recorded its response. Both the stimulation and recording periods lasted only a fraction of a millisecond, depending on the speed of the turntable. The temporal offset of the stimulus and recording epochs could also be changed by adjusting the angle between the two switches. By varying these parameters and averaging over many trials, Bernstein built up a full picture of a single action potential in a frog nerve.
After this achievement, Seyfarth describes how Bernstein went on to formulate an eerily prescient “Membrane Theory of Electrical Potentials”, based on the predictions of the hauntingly familiar Nernst equation. It’s insane how right Bernstein was most of the time. Maybe it’s just that his stupid ideas and shitty experiments were forgotten? It’s hard to say, but Seyfarth attributes Bernstein’s stellar accomplishments to his unflappable attention to detail.
Bernstein is great, but Seyfarth deserves a boatload of credit here too, for illuminating Bernstein’s illustrious career and writing it down in this sick historical pape. Now that he’s retired, I hope that Dr. Seyfarth returns to the archives to dig up more sick historical anecdotes about neurobiologists of yore.
Sick Papes sat down with Jonathan Tang to discuss his recent paper “A Nanobody-Based System Using Fluorescent Proteins as Scaffolds for Cell-Specific Gene Manipulation.” Sick Papes also did this interview the old fashioned way, like an idiot, by recording and transcribing rather than emailing and relaxing. Hence the big delay. But like rediscovering a bottle of once lost liquor in your dirty clothes pile, you should be excited: Jonathan took advantage of antibodies from a camel to make GFP – the head honcho fluorescent protein for cellular visualization – friggin’ functional, as the key scaffolding ingredient in a threesome of transcriptional hedonism. He calls these nanobodies “transcription devices” and if you F with GFP, you better start getting creative.
Jonathan Tang et al. 2013. A Nanobody-Based System Using Fluorescent Proteins as Scaffolds for Cell-Specific Gene Manipulation. Cell 154, 928–939
SP: I’d like to start this interview with a quote from the movie Nacho Libre. Have you ever seen Nacho Libre?
SP: Okay well it’s a movie where Jack Black plays a Mexican wrestler and at one very important point in the movie he says, “Under the clothes we find the man and beneath the man we find… his nucleus.” What type of man are you and what’s up with your nucleus?
JT: Okay. I guess on the surface I’m pretty shy person. Underneath I am someone who wants to change the world. And my nucleus? I hope it’s functioning well, with little UV induced damages.
SP: You’ve invented a technology for retrofitting transgenic organisms called “transcription devices dependent on GFP.” Can you explain GFP and “transcription devices” to our readership?
JT: GFP stands for green fluorescent protein, it was discovered in a jellyfish 40-50 years ago and emits green fluorescent light. GFP has been put to use as a tool in molecular biology since 1994, allowing researchers to tag proteins and visualize cellular processes. This has been a powerful, Nobel prize winning tool for researchers. Regarding “transcription devices,” that’s a fancy name I gave to an engineered, hybrid transcription factor. The idea is to make the device activate transcription, but only when its two independent protein parts are tethered to GFP. If GFP is present in the cell, the device be fully formed and functional to initiate transcription in a downstream gene of interest.
SP: Most SP readers have a 3rd grade education. How would you explain this technology to a 3rd grader?
JT: I don’t know if a 3rd grader would understand genes, but here it goes: the transcription devices are present throughout an organism but remain inactive except in cells with GFP. In these cells, devices tether themselves to GFP and initiate events inside cells to turn on other genes.
SP: How does this interaction actually work?
JT: It’s based on protein-protein interactions. The devices are binding proteins derived from camel antibodies that bind to GFP with high affinity. The reason why we use camel antibodies is because the antigen recognition domain is contained in a single peptide segment. Conventional antibodies are hard to express in cells as they are made of two proteins joined by a breakable disulfide bond. I found that there were pairs of the these camel antibodies that recognized different parts of GFP and could co-occupy GFP. This allows one to simultaneously tether different protein domains on to GFP. In this case, I tethered a DNA binding domain with one camel antibody and a transcription activation domain with another. GFP is then the scaffold for forming an active transcription factor which can then initiate transcription of any gene of interest downstream of its genome binding site.
SP: It seems like you kind of owe the camel a lot. Pretend I’m a camel. What would you like to say to me?
JT: I guess for the sake of the next Nature paper, tell me why you evolved single chain antigen binding domains. Please tell me that. If you do, I’ll pay you back with a lot of water.
SP: Like middle-author type water?
JT: Like a gallon of water. Other than that, thank you very much you solved my problem.
SP: At any point in your project, did you make a scale model of GFP in your kitchen to try and identify where the transcription devices would bind?
JT: Not quite like that, but I did do a look at a lot of crystal structures and computational models of GFP structure, along with the structures of the GFP binding nanobodies. I just kept trying to fit them together. Turns out it was a waste of my time, because in the end I had to empirically pair-wise test all 6 nanobodies.
SP: How happy were you when you found a pair that worked ?
JT: I was pretty happy actually. I was in the lab at like 5 o’clock in the morning (editors note, JT is a confirmed night owl) and there was nobody around. I was just so happy, but there was no one to tell. Then my adrenaline went up and I walked around the building looking for people to tell but there was still no one. So I went back to work.
SP: That was a breakthrough moment in the project?
JT: Yes. There was no way to know if the system would work at all. I only had the six nanobodies which were generously given to us.
SP: It’s amazing how a couple of hours of positivity can energize us to wade through a swamp of disappointment that can last years.
JT: That’s true. Prior to that moment there was a lot of disappointment.
SP: Did you try other systems?
JT: Yes, I tried to make a Cre recombinase into a GFP-dependent into Cre recombinase. It was a naïve idea. But those experiments were helpful, as they did told me that the nanobodies could direct GFP to distinct compartments in the cell. That was the first clue the reagents I had could tether GFP.
SP: How do you think about, or visualize, these high affinity interactions between the nanobody devices and GFP? Like a key in a lock? Bugs on a windshield?
JT: Yes, I think of them as locks and keys, they simply come together. Without the high affinity, I don’t think it would work very well.
SP: One of my favorite things about this paper is that the technology that’s developed is not only an important proof of concept, but is immediately of practical use. What is the current utility of your GFP nano-bodies? Where do you see this technology going forward?
JT: One of the exciting applications is for retrofitting transgenic GFP animals. Many GFP lines have been engineered to express GFP in genetically defined populations of cells. For example, the GENSAT (http://www.gensat.org/index.html) project has over 1,500 mouse lines for labeling neuron populations in the brain and retina. Now the question is can we use these nanobody devices to perturb function in GFP expressing cells. One idea would be to turn on the light-sensitive ion channel channelrhodopsin in GFP expressing brain cells to make these neurons fire action potentials with light. As we show in the paper, with this technology you can probe the downstream brain circuitry from the cells that were previously only visualizable. In the long term, this paper suggests that GFP itself is a great transgene. Because it can be used for anything. You can imagine building many types of synthetic systems that use GFP to turn on or off different cellular processes, by mating GFP animals to other animals carrying nanobody devices or by introducing these devices with viruses.
SP: Have you thought about targeting your transcriptional devices to other proteins too?
JT: You mean using other proteins for turning on the system? That’s something that we’re looking into doing.
SP: One more question for you, on behalf of the molecular aficionado readership: In your paper, you note that there are pros and cons to your devices vs. traditional recombinases for manipulating genomes. Can you explain those pros and cons?
JT: The current system uses three components to form the hybrid transcription factor. While this is not as efficient as functional single molecules like Cre, it does have the ability to achieve more specificity through intersectional expression of the individual components. The other problem we experienced was having too much GFP, which sequesters individual nano-devices without the paired binding necessary for transcriptional activation. So the nano-devices have to be tested with each transgenic line. Unlike with Cre, which tends to enact permanent changes in a cell and its progeny, this system can also be reversible, dependent on the continued presence of GFP.
Thanks Jonathan you’re the man!
SICKPAPES SPECIAL EDITION ON SUPPLEMENTAL DATA!!!
Supplemental Text 1 from:
Deshpande, G., Zhou, K., Wan, J.Y., Friedrich, J., Jourjine, N., Smith, D., Schedl, P., 2013. The hedgehog Pathway Gene shifted Functions together with the hmgcr-Dependent Isoprenoid Biosynthetic Pathway to Orchestrate Germ Cell Migration. PLoS Genet. 9, e1003720.
Like many people, I have conflicted views about the reams of Supplemental Data that accompany the online versions of most papers published these days. At its worst, Supplemental Data is nothing more than a grainy video of a bat performing fellatio, overdubbed with thumping techno. At it’s best, however, a truly great Supplemental Figure reminds me of the famous scene in When Harry Met Sally where Meg Ryan loudly fakes an orgasm in a crowded restaurant, except that for me, the orgasm is real, and in those moments of ecstasy I am neither woman nor man but purely divine flesh of the GodBody incarnate. This Supplemental Text Document right here is one of those good ones which make me very glad to be living in the “Era of Supplemental Data,” as it was recently dubbed by Francis, the first pro-Open Access Pope.
To be real with you, I’ve never seen a Supplemental Document quite like this one. While Supplemental Data most often includes extra methodological details, additional controls, large datasets, or tangential experiments requested by reviewers, this one is a long-form prose essay about a decade-old scientific disagreement between these authors and a different lab. We here at SickPapes don’t take sides in this quagmire - both of these labs are outrageously hot and time-tested - but we find it surprisingly compelling to read such an emotionally honest and open piece about a genuine scientific disagreement.
Our story begins in 2001, when Paul Schedl’s lab published a paper in Cell providing evidence that a secreted protein called hedgehog is involved in guiding embryonic germ cells as they migrate towards the future gonad. In one key set of experiments, they ectopically expressed hedgehog in abnormal locations, and showed that germ cells migrated incorrectly. This was interpreted to suggest that hedgehog is sufficient to influence germ cell migration.
As far as the public was concerned, the next thing that happened was In 2007, when Ruth Lehmann’s lab published a rebuttal, with the unambiguous title “hedgehog does not guide migrating Drosophila germ cells.” In the Lehmann lab, the hedgehog ectopic expression simply did not affect germ cell migration as it did in the hands of the Schedl lab members. This was not a matter of subtle differences in methods, this was literally a direct repeat of a simple experiment, giving different answers. Both labs are highly respected, and this discrepancy was hard to explain without getting a tad bit disrespectful.
Which brings us to explaining why this new Supplemental Essay from Schedl’s lab is so sick: it explains what was happening behind the scenes at Cell the whole time. First, they reveal that the Lehmann lab’s 2007 paper actually originated as a technical comment sent to Cell in 2002 in response to the original 2001 article. The Cell editors asked the Schedl lab if they wanted to retract their paper, and the Schedl lab said “No.” Instead, they came to an agreement with Cell that an outside, independent researcher would repeat the hedgehog experiments, communicating only with Cell and not with either of the labs in question (Shout out to Stephen DiNardo, stepping in to do a major solid for the scientific community without any personal glory).
After an extended drum-roll, Dr. DiNardo told Cell that his independent experiments confirmed the original results from the 2001 Schedl lab paper, not the Lehmann results. So, what does Cell do with this important finding? Nothing. Instead of publishing this informative back-and-forth, they didn’t make any of this public, and just let everyone gossip for a decade. And, according to the Schedl lab in this Supplemental Text, this gossip-filled silence has “undermined [their] credibility in the scientific community, jeopardizing [their] careers.” Damn, Cell - that is some cold shit. I wish more folks would publish Supplemental Emotionally Honest Essays detailing the strife that various journals put them through. At the least, this might add fuel to Randy Schekman’s dope protest against journals like Cell.
With that, we here at SickPapes wish to salute any and all Sick Supplemental Data, and wish you a very happy 2014!
Clarke et al (2013). Detection and learning of floral electric fields by bumblebees. Science 340 (6128): 66-69
Greggers et al (2013). Reception and learning of electric fields in bees. Proc R Soc B 280 (1759).
Year in and year out since the beginning of time, the amber fields of research programs across this great land are sprinkled with NSF fertilizer and grow the science crops that feed our hungry brain-mouths. While most days we feed our bloated carcasses on the high fructose corn syrup of the mind, every once in a while, you fill your cow horns with the right kind of manure, nail the astrological planting cycle and BLAMMO! - when the research harvest comes in, it comes in big. Well, it’s a boom year and the organic veggie du jour is bee learning and cognition. Here’s just one hors d’eouvre to whet your appetite:
My most vivid memories of childhood summers come from wandering along the Maine coast listening to my Aunt describe the auras of unwitting passersby, from “deep-blue” for the kid on a skateboard, “wispy green” for the owner of the Life is Good shop, and “surprisingly rectangular camo-colored” for the potbelly-sporting middle-aged man with a warm Budweiser and a Kiss lunchbox. Like these divine beach-goers, all living things (including the most heartless beasts of all creation: plants) give off subtle electrical fields. Despite its profound implications for literally everything, research on electric field perception has been mainly restricted to publications in Frontiers in Quack Science and F1000’s “What the $&*% do we know?” section. Two recent papers, though, are finally lending heft to the otherworldly electro-perceptational abilities of bees.
Up first is a sick pape showing that bees can sense electric fields created by plants. By creating artificial flowers (“E-flowers”, or E-cigarettes for bees) where they could measure and manipulate the electric field, Clarke and friends showed that bees can learn to differentiate between flowers that are completely identical except for their electric field. Mind-blowingly, the mere presence of the bee near a flower also changes the flower’s electrical pattern, so bees may be able to use their aura-sniffing abilities to figure out which flowers have been recently cleaned out by some other nectar-hungry bee.
While this study definitively showed the presence of the Third Eye in bees, more questions are raised than answered: Does the third eye align with the seventh chakra? Can the NSA use it to track my Private Browsing content? What causes Third Eye Blindness?
Thankfully, in a case of cosmic alignment, within a couple of weeks of this pape coming out, YET ANOTHER sick pape from a totally separate group gave us insight into how this might work. Coulomb’s law states that two charged particles will exert a physical force upon each other. Since insect antennae carry a charge, they could theoretically move in the presence of an electric field, allowing bees to perceive these electric fields.
In a beautiful series of “set em up and knock em down” experiments in our second sick pape, Greggers and amigos showed that bee antennae move in response to electric fields and that these movements juice up some specific neural pathways that allow the bee brains to perceive electricity. Indubitably sick.
We here at SickPapes have obviously spent the past several years reaching out to a wide variety of porno mags, with hopes of initiating a collaboration. Our goal was simple: to use our vast fame and influence in the scientific community (and beyond) to call bullshit on the troves of “evolutionary psychology” pop-science out there about human sexual behavior, which we feel often lacks a certain je sais exactly quoi called “data.”
When we finally met MOMMA TRIED, we were ecstatic. MOMMA TRIED is a “literary nudie mag” which aims to appeal to all sexualities and types of people out there.
For their first ever issue, we interviewed Dr. Vincent Lynch about the evolutionary ideas surrounding the female orgasm, particularly on the elaborate just-so stories that societies have concocted to explain the apparent differences between the male and female orgasm. Dr. Lynch is an outrageously sick molecular biologist who has given birth to a beautiful series of papes on human evo-devo, many about the evolution of pregnancy. As a graduate student, he wrote a single-author take-down of a particularly suspect dataset, and it was incredibly rad of him to sit down with us.
To read this exclusive interview, you’ll have to order this physical, glossy, nudie mag from this website. Or, if you’re in New Orleans on November 23, 2013, you can go to their launch party!
Have fun everyone!!
Dunlap, K. and Mowrer, O. H. (1930). Head movements and eye functions of birds. J. Comp. Psychol. 11, 99–113.
People make a lot of hay out of the series of photographs by Eadweard Muybridge that Governor Leland Stanford commissioned to figure out whether all four hooves of a galloping horse are airborne at the same time. Muybridge ingeniously used an array of cameras that were triggered sequentially by the horse busting through a series of trip wires. The result of this experiment was that there was definitely a moment in the horse’s gait when all four feet were off the ground. (Stanford went on to found the university that produced Olympic water polo player Tony Azevedo; Muybridge ended up shooting a man who slept with his wife, but was acquitted on grounds of “justifiable homicide”.)
Now I don’t want to dump on the birth of cinema, but I’ve just been out watching horses gallop around all morning, and I’m pretty sure that I could reproduce Muybridge’s experiment with some study drugs and a mug of properly mulled cider. Things are always clearer in hindsight, but it didn’t take much squinting to convince me that horses are airborne every quarter second or so. Perhaps Muybridge and Stanford were half blind from living in an era before proper sunglasses, or maybe horses were faster in the 19th century because there were no clocks and all the conductors had to count continuous Mississippis to keep the trains on time.
Whether or not the Muybridge horse study was necessary, subsequent developments in rapid picture-taking have proven incredibly useful for the study of biomechanics. Today I want to discuss an early example of how the camera can be used to compensate for the inability of us humans to fully appreciate animals.
Many people have wondered, “What’s up with pigeons bobbing their heads all crazy while they walk”, but most people are too afraid to blog about it. As Dunlap and Mowrer, the authors of today’s sick pape, put it, “The forward and apparent backward movements of the head which pigeons, chickens, and certain other fowls display while walking have been commented on by various persons orally, but seldom in print.”
It may have occurred to you that this jerky head movement is an accident of the pigeons walking gait, perhaps analogous to the swinging of a human’s arms. But this is wrong. In 1930, Dunlap and Mowrer took some great photos that proved that bird head bobbing is just an illusion. In fact, it is you, the viewer, who is lurching ferociously back and forth, and the bird is perfectly motionless! That’s not actually true. What is really happening, Dunlap and Mowrer found, is that when the bird’s body is moving, the head is completely still. In other words, the head is locked in position relative to the forward moving body. Then, when the body stops for a brief moment, the head thrusts rapidly forward to a new position. So, overall, the head is maintained in a stable position relative to the body. The stroboscopic photo above, from a sick follow-up pape by B.J. Frost in 1978, illustrates this nicely.
This head stabilization has obvious benefits for vision, as it is much more difficult to analyze a visual scene when your head is shaking. Another set of experiments by B.J. Frost in the 70’s clearly demonstrated that head-bobbing is controlled by vision, as pigeons walking on treadmills don’t bob at all (because the visual scene is stationary).
The findings of Dunlap and Mowrey in 1930, and subsequent work by B.J. Frost and other enthusiastic bird bio-mechanics, are a superb example of how the world is incredibly fast and confusing, and only photographic magic and detailed quantification can distill truth from all the chaos.
Sick Papes salutes those review article figures which take a Daoist approach to cellular biophysics and molecular mechanics (Larkum Nat Neuro 2013)