Hastings, J. W. (2001). Fifty years of fun. Journal of Biological Rhythms. (Vol. 16, pp. 5–18). [PDF]
Woody Hastings, who passed away last week at the age of 87, ran his lab down the hall from where I worked as a graduate student. He was already retired by the time I began, but over the years I would occasionally pass him in the hallway, where he still kept an office with his name on the door. I had no idea who he was or what he had studied, but for some reason a few months ago, I decided to look him up online, to see what this friendly older man in a plaid lumberjack coat was all about. And I say to you now the same thing I said then: Holy Shit.
Dr. Hastings’ career was so outrageously inspiring and self-evidently meaningful that it’s hard to know where to start. For his entire career, he studied the coolest thing on earth: bioluminescence. That’s right, Dr. Hastings spent his life studying the things that the rest of us dreamt about last night: swimming through a glow-in-the-dark ocean, lying in a field of fireflies. The title of his memoir-pape is literally “Fifty Years of Fun.”
You might imagine that glow-in-the-dark bacteria is some sort of trippy side-show to Mainstream Molecular Biology, but in fact the Hastings Lab’s studies of bioluminescence led to a baffling number of fundamental biological breakthroughs. Most famously, the Hastings Lab was the first to describe quorum sensing (which they called “autoinduction”), the means by which bacteria communicate and interpret their population density. For bioluminescent bacteria, quorum sensing is important because the glow is only visible when bacteria are at present in large numbers, so these microbes need to be able to coordinate their glow-making gene expression based on population density. Thus, the Hastings’ lab gave the first evidence that gene expression could be directly regulated by signals sent by other bacteria. We now know that quorum sensing is widely used by bacteria, and is important for such medically-relevant phenomena asbiofilm formation, virulence, and antibiotic resistance.
It is important to realize that Hastings was working at the same time (and place) that the molecular biology revolution was occurring, when many now-famous scientists were figuring out transcription, translation, the genetic code, and gene regulation. But those scientific giants were a real clique, and Hastings was not really on the inside. Jim Watson, who founded the department that Hastings’ worked in, wrote: ”Woody was liked by all…though I saw his science as having little potential to make lasting ripples.” Wally Gilbert, who also worked in the same building as Hastings, ”expressed disbelief or disinterest, or thought [the] findings had a trivial explanation.” Basically, if you weren’t studying E. colior phage genetics, your work wasn’t seen as relevant. Of course, this arrogant attitude is fucking ridiculous, both then and now. Hastings’ career is proof that it is not true that “model organism” research is the only way to get down to the heart of things (though of COURSE, Sick Papes also worships E. coli and phage, don’t get me wrong - just saying that they are just as “weird” as any other organism.)
And there’s much more. Hastings’ work was also foundational for another entire field: circadian rhythms. He showed that bioluminescent dinoflagellates have an internal clock, and provided one of the first tractable systems for studying the biochemical basis of biological rhythm. And again, this work has proven to be fundamental across much of life, including humans.
Hastings also pioneered studies of many interesting bioluminescent organisms, including the now well-known symbiosis between bioluminescent bacteria and squid, where the squid use the glowing bacteria in their belly to optically match the down-pouring moonlight and thereby make themselves invisible to lurking predators beneath. Yet again, Hastings provided one of the first tractable experimental systems to help found an entire field that might seem at first glance to be a novel sideshow, but has since exploded into an NIH-funded, power-house of mega-important research on the microbiome. Glowing oceans, the rhythm of life, and symbiosis - that’s how you do it. And it is a testament to Hastings’ scientific brilliance that all of these studies of unusual organisms were so solid that they helped to spawn entire fields that are still going strong decades later.
As we pay tribute to Woody Hastings, I’ll leave you with a quote from “Fifty Years of Fun,” where Hastings’ gives a memorable metaphor for the sometimes unituitive process of evolution:
"[A] story of inanimate evolution, which I picked up at JPL, the Jet Propulsion Lab at Cal Tech… It concerns the origin of the track width of railroads in the U.S., which is exactly 4 feet, 8.5 inches. The first explanation is that English expatriates built the first railroads in the U.S., but where did the English standard come from? Obviously from wagons and carriages, for which the jigs and tools were readily available. And why were they built that width? Because with any other spacing the wagons would break up on some of the old long-distance roads, due to the existing wheel ruts. These can be traced to the Romans, who built and used these roads for their war chariots, designed to be just wide enough to accommodate two war horses, thus accounting for the width. As with living organisms, many present-day features were determined long ago.
JPL provides another twist to the story. Attached to the space shuttle there are two large booster rockets, made by a factory in Utah and shipped by train to the assembly site. The rockets were built as large as possible, but they had to pass through mountain tunnels, the sizes of which are related to track width. So a major design feature of the world’s most advanced transportation system was determined by the width of a horse’s ass.”
Yen, J.H., Barr, A.R., 1973. The etiological agent of cytoplasmic incompatibility in Culex pipiens. J. Invertebr. Pathol. 22, 242–250.
Since our last post, two months ago, we here at Sick Papes have been riding the highs and lows of an almost indescribable emotional voyage from which we have only recently emerged, bursting with joy and self-knowledge.
It all began, like most of our emotional experiences, while we were blasting the Chances With Wolves radio show (which, in case you don’t know, plays the best music on the planet) at full volume while dissecting crickets under a microscope. All of a sudden, a song by Jonathan Richman called "Fly Into the Mystery" came on. This song, like many others by Jonathan Richman, is about the beauty and longing of summer nights in Boston. And it began to haunt me.
Driven by an unknown urge, I embarked on a literature search of other beautiful things that have happened on Boston summer evenings. This obviously led me to this 1924 pape, where two dudes took a break from their Great Gatsy-era shennanigans to look through a microscope for one GodDamn second an observe a strange bacteria living inside the ovary cells of the mosquitoes living around Boston and Brookline. These bacteria, subsequently named Wolbachia, remained mostly a curiosity for the next 60 years, thought to only exist in a handful of insect species. It wasn’t until the 1990s, when dudes figured out how to use molecular methods to identity cryptic bacterial species, that the trippy truth emerged: Wolbachia infect ~1 million species of insects (and other arthropods and nematodes), and are probably the most abundant endosymbiotic bacteria on the planet. And more importantly, their insane evolutionary success is largely because they can directly manipulate the reproductive behavior of their hosts.
Somes jokes, like the one about re-captioning every single New Yorker cartoon with “Christ, what an asshole!” stay hilarious no matter how many times you hear them. And it’s the same for some research topics: as far as I can tell, every pape that has ever dropped about Wolbachia is fucking amazing. It was in the vortex of insanely hot papes about Wolbachia that we have been trapped for the past two months, unable to stop clinking through to other hot references. It’s pointless to try to pick the best of the bunch, but this 1972 pape right here is straight up astounding. (OK, Wolbachia weren’t totally ignored until the 1990s, but they were definitely a left-field kinda thing.)
The background is that different populations of mosquitoes from around the world often can’t successfully mate with each other. This isn’t really a mind-blower - it’s the early stages of speciation, where the different populations still look like the same species, but their genomes have independently evolved to the point that they can no longer fit together quite right when they mate.
What IS a mind-blower is that, in this case, the reason these different populations can’t reproduce is because of the specific strains of Wolbachia that live in the ovaries of the different populations. If you simply feed the mosquitoes antibiotics, all of a sudden they can reproduce with the other populations. In other words, the Wolbachia bacteria is causing the formation of new insect species. This is also the case in Nasonia wasps, where three totally different species instantly become interfertile if you give them antibiotics.
Hödl, M., & Basler, K. (2012). Transcription in the absence of histone H3.2 and H3K4 methylation. Current biology : CB, 22(23), 2253–2257. doi:10.1016/j.cub.2012.10.008
Pengelly, A. R., Copur, Ö., Jäckle, H., Herzig, A., & Müller, J. (2013). A histone mutant reproduces the phenotype caused by loss of histone-modifying factor Polycomb. Science (New York, NY), 339(6120), 698–699. doi:10.1126/science.1231382
Biology is bursting at the seams with controversy. By far the most important controversy in modern biology is whether taking steroids makes your penis smaller, or whether this is just some D.A.R.E. bullshit they told us as kids to prevent us from fully achieving the glorious manifestation of our god-granted, muscly-man physiques. For those of us who believe that, in fact, steroids may help the enlarge the penis, a sub-controversy exists over whether one should inject the steroids directly into his or her penis. (Answer: currently up for debate on numerous message-boards.) Our colleagues have recently dubbed this expanding field “Penomics,” and we believe it to be rife with promise.
Arguably the SECOND-most important controversy in modern science is related to the importance of histone modifications in gene regulation and epigenetic inheritance. Here’s the low-down: DNA is a linear molecule, but is physically wrapped around structures made of histone proteins (the entire group of histones is collectively known as a “nucleosome”). The histone proteins can be modified at specific amino acids by the addition or removal of chemical groups such as methyl-, or acetyl-, which may help them physically move so that a given piece of DNA is “unwrapped” from the nucleosome and becomes relatively available for transcription.
While there is undoubtedly a strong correlation between histone modification and transcriptional activity, skeptics have pointed out that there remains very little definitive proof that histone modifications are causally important for the regulation of the nearby DNA (i.e. whether a gene is “turned on” or not is influenced by the modifications on the nearby histones). Despite this uncertainty, many writers have gone way overboard and claimed that histone modifications represent the ultimate secret key by which gene regulation is maintained across multiple generations. The masturbatory frenzy of celebration around this field has recently been strongly criticized by the God-like Mark Ptashne in a blunt letter he wrote to the Proceedings of the National Academy of Sciences.
The reason that there is so little direct evidence for the function of histone modification function is because histone proteins are exceedingly difficult to alter in vivo. This is because there are 23 copies of the histone genes (in fruit flies). What are you crazy sons-of-bitches gonna do, mutate ALL of them at once? In fact, yes. Some ambitious lads and lasses took advantage of the fact that these 23 histone genes all lie physically next to each other on the chromosome, and they built a fly with a large chromosomal deletion spanning this entire region. Then, by adding in mutant histone proteins (which, for example, cannot be chemically modified at a specific amino acid), they can ask whether this specific amino acid modification is actually necessary for the histone function.
These two papes present very similar experiments, but report essentially opposite conclusions (sort of). In Pape 1, dudes make a fly whose entire complement of Histone3 cannot be methylated at Lysine #4 (which has been proposed to be required for active transcription at a given genomic site) - i.e. every single nucleosome along the entire genome of a given cell contains histone3 that can’t be methylated at this position at all - and yet they find that these cells can transcribe perfectly fine, and express all the right genes. In other words, methylation at H3K4 cannot be causally required for transcription. Ooh chi wally wally!
But then Pape 2 (Pig in the City) chimes in with a very similar fly, but whose Histone3 cannot be methylated at lysine #27 (another site proposed to be essential, this time for repressing genes). In these motherfucking flies, the cells have completely screwed up gene expression, exactly mimicking the effect of removing the methyl transferase that adds that methyl group. Ooh chi bang bang!!
The debate rages, dudes are battening down the hatches, and our blood-soaked tax dollars continue to fuel this Amazing Race. Me personally, if I have to take sides, I bet that histone modifications are causally important, but this feeling is entirely uninformed, its just my personality!!!
Gymrek M, McGuire AL, Golan D, Halperin E, & Erlich Y (2013). Identifying personal genomes by surname inference. Science (New York, N.Y.), 339 (6117), 321-4 PMID: 23329047
For most of us, David Golann became a household name when CNN caught him heroically saving the life of a terrified rat stuck in New York City traffic. (“I just sort of know what it’s like to be pretty scared.”) So it was not surprising this week when several thousand fans wrote in to ask if this was the same David Golan who appears as third author on this crotch-kickin’ Pape which burst forth onto the earth-realm last week. To which we reply: thank you for writing, but, no, these two men spell their names differently.
But on the topic of last names, there are now manyservices that allow folks to try to identify the last name of their biological father via DNA testing. For these sites, you send in some DNA, and they examine sequences on the Y-chromosome (which are inherited only from your father), and then they look for the closest match in their big ol’ sequence databases. While they probably don’t have your father himself in their database, they are likely to have several distant patrilinear relatives, and by analyzing those names, they can hypothesize the likely last name of your father, and apparently with pretty good success.
What the Foot Clan-esque authors of this pape realized is that these publically available databases allow hackers to identify the names of the “anonymous” genomic databases that are increasingly available on the internet. The basic algorithm is: submit the Y-chromosome data from these supposedly anonymous genomes to the paternity websites, which gives you the most likely last names. At this point, you’ve narrowed it down to ~40,000 individuals. Then, parse through these candidates using two other publically available pieces of information (D.O.B. and State of residence), which typically narrows it down to about 12 males. At which point, you are fucked.
Basically, these dudes are like Robert Redford’s gang in Sneakers: they hacked the system not to do harm, but to show us the system’s weakness. I mean, it only works on males and it doesn’t work all the time, but it’s still NASTY!!!
Schwager, E., Pechmann, M., Feitosa, N., McGregor, A., & Damen, W. (2009). hunchback Functions as a Segmentation Gene in the Spider Achaearanea tepidariorum Current Biology, 19 (16), 1333-1340 DOI: 10.1016/j.cub.2009.06.061
Khadjeh, S. et al. Divergent role of the Hox gene Antennapedia in spiders is responsible for the convergent evolution of abdominal limb repression. Proc Natl Acad Sci USA 109, 4921–4926 (2012).
Even in my wildest imagination, I could not have dreamed up a stupider fucking abstract than this one, where two halfwit cretins claim that there may be a single gene associated with credit card debt. I will give you a moment to let the infurating constellation of ahistorical classism and racism sink in (did you also find the gene for not having health insurance? for working three jobs?), while I practice my deep breathing exercises, chief a one-hitter to my dome, and prepare my loving thoughts on two ACTUALLY MEANINGFUL studies on the astounding effects of single genes. Namaste, true researchers of the embryological process.
Now then. Although I cannot mask my disappointment that it has taken 2012 years, I am nonetheless ecstatic to report that humankind has collectively figured out how to make four-legged spiders (Pape 1, see video) and ten-legged spiders (Pape 2). And the crazy thing is that in both cases, these massive changes are the result of removing a single gene from the spiders. Of course, these single genes encode for those powerful regulatory proteins that act very early in development to organize the collective activities of hundreds of other genes later on to generate large portions of the body.
For more information on the actual, non-intuitive relationship between genes and biological reality, I encourage you all to read up on my favorite experiments ever done.
On this first birthday of the venerable institution that is Sick Papes, let us take a moment to reflect how far we have come since 2011.
Only one year ago, the number one Google Hit for “Sick Papes" was the rueful tale of an honest dude getting sick from see-through papes. In less than a calendar year, Sick Papes has clawed its way up the Google rankings, leaving discussions of unfortunate soup/pape interactions dry-heaving in the dust.
Thank you, dear readers, for all of your financial and emotional support. We have only just begun.