Puns aside, today has certainly been a “big” day in human genetics. Following the initial discovery of isolated human genetic variants that affect height, several new reports in Nature Genetics isolate as many as twenty common loci that may provide yet another explaination why your child will never get into Harvard, or make enough to pay for your retirement.  In the midst of culling through the finding, however, the Pasigraph noted an interesting geopolitical aside in some data: glory be, even PhD trained Europeans still love America, and would dock their boats at the ledge of the Statue of Liberty in a heartbeat.

While seeking out Hipster-worthy dubs to describe their findings, a consortia based in the stuffy UK has relented to calling one particular vantage point of common variant studies “The Manhattan Plot“. So either it’s hard to remember any islands in Europe which are longer than they are tall, or Euros still yearn to conduct their useless science in a place where costs woefully outstrip the puny remittance they receive to decipher the genes responsible for Shaquille O’Neal.

The Pasigraph notes this isn’t the first time we’ve seen city-envy creep into scientific forums…we diligently referred to the last metastasis we had as “going Uptown“.

1988:

“It is likely [expression of a single gene] in a fibroblast is sufficient to confer V(D)J recombinase activity on that cell”

“Our data suggest that transcriptional inactivation or post-transcriptional down-regulation of the RB gene may be important in the etiology of some osteosarcomas and soft tissue sarcomas as well as retinoblastomas.”

 1978:

“…the state of the virus DNA in transformed cells is different from that of DNA in virus particles”

“Whether further translocation of [insulin] occurs is unclear and has not been investigated by direct means…”

 1968:

“It would be useful if computers could learn from experience and thus automatically improve the efficiency of their own programs during execution.”

“Astrocytes in cultures of brain cells from fetal or newborn hamsters undergo neoplastic transformation after infection with simian virus 40 or polyoma virus”

Ah, how complex life has gotten, what with Shoe-Bombers, Dirty-Bombers and Guys Who Don’t Bomb Anything But Kill Us With Powder. Wouldn’t it be so nice to get back to the pleasant, yet eccentric, joys of nuclear winter? Well, just slightly after the holidays, the Pulitzer Prize winning Richard Rhodes delivered a talk at the GooglePlex regarding his new book, “Arsenals of Folly: The Making of the Nuclear Arms Race“.

It’s a long talk, but worth the time and worth taking notes. We learn how Robert McNamara, having already made numerous decisions costing somewhat-countable American lives, almost doltishly brought the whole biosphere to collapse. We see again and again why exactly Pakistan is the scariest place in the universe (sorry, Danny Pearl and Benazir).  And it’s always fun to know what’s been happening with the folks who have worked in the long wake of Carl Sagan’s death. Mostly, however, we’re glad to be in the temporary company of someone who knows that a marble of plutonium weighs a kilogram. Here’s to imagining those 400MPH fire-winds and EMPs while we fall asleep tonight. Thanks Richard…we here at the Pasigraph will keep buying your books all the same!

In the March 21st issue of Science, uber-hipster science journalist Elizabeth Pennisi casts a mega-watt investigative bulb on a issue of un-paralleled significance to science. Dying bats? Dying bees? Atmospheric forcing? Higgs particles? Nope. Readers, rally your villagers to take up arms, light torches, and we all storm the monster’s castle at midnight: scientists are fucking up their submissions to the DNA database Genbank, and the computational fungus biologists are pissed about it!

See, apparently anecdotal evidence suggests busy fung-ologists rush to submit their DNA sequences to Genbank (usually at the behest of journals where they want to publish), and erroneously record the precise lineage of species they’ve sequenced. While that’s fine and dandy for bench scientists, it basically threatens to put lazy computational mycologists out of business by making their shitty meta-analyses of databases derived from wet-bench scientist labors (more) FLAWED AND USELESS. And these brats take out their fury in a full letter to the editor from this issue.

Fine, you would say, but the bitchy under-dogs quickly draw support from an all-too-typical source: journalists and editors at scientific journals. This particular heroine, Elisabeth Pennisi, dedicates a whole mind-numbing News and Views article to the subject, mostly because it exposes a pet project issue near and dear to the hearts of journalistico’s and editors: cross-pollinate the bleeding-edge aspects of science, technology and culture, and people will pay attention to you (the journalist) and think you’re out there for the human good (and not just yourself, the journalist). In short, she portrays the fung-ists efforts as a step to “Wiki-fy” our bioinformatics databases…and who could possibly take issue with that ever-so-reasonable stance?

But alas, in any story like this there must be a villain, and Pennisi goes pretty far afield to find a reliable arch-enemy: computational biologists at the National Center for Biotechnology Information (NCBI)! These bastards have long suppressed the hopes and dreams of sequence analyzers and Perl-sters, and are not nearly as good looking as their European counterparts. Bunkered down in their bomb-proof fortress headquaters, the fascist IT-ers quash the hearts of all Wiki-wannabes, and spew invective from bullhorns to the effect of “I think it will be solved eventually…” Indeed, NCBI-ists, we have heard this all before…but usually from the Reichstag.

Feisty Commie Fascists and their victims aside, Pennisi ignores how the Genbank databases pussy-whip the size, scope and growth of something as puny as English Wikipedia, which at the moment could still squeeze onto a double-sided DVD and leave room for a Farrelly brothers film. Also, she fails to mention the daily horrors involved in maintaining accuracy of open-media repositories, the worst examples of which seem to involve the very people who exercise most control over the resource. Remember, bioinformatics databases are already complex enough to be interesting at the GooglePlex and they are heroically stewarded by a miserly user-base who, if chopped up and made into stew, couldn’t feed but a fraction of the maniac denizens who argue in the annals of Wikipedia.

Pennisi wastes our time in tromping out a predictable lede and faux-dramatology structure to point out an issue that will be resolved over coffee by a few computer scientists at a conference session break. If you think we’re just being ornery and unfair to fair Elizabeth, then read on to very next Letter to the Editor, which dutifully wrestles with another News and Views pertaining to a somewhat more troublesome issue and organism, Plasmodium.

The Pasigraph will make regular postings on a topic familiar to us all. As mere plebes, we fleetingly encounter some very peculiar animals of science. This breed is notable for: breezing past the editorial board; being peerless in peer-review; breaking the study section’s back; filching from venture capitalists like a hooker from her John; making the tenure committee weep; getting the folks in Stockholm itchy to pick up the phone and call them; and generally squeezing the scientific oxygen out of the very rooms in which we try to breathe.

Friends, to document these beasts before they devour us whole, we present the Sonic Hedgehogs (SHH). Every so often, we’ll delve into the lives of scientific wunderkinds to ’suss out their victories, their embarrassments and record the names of the people who picked on them in middle-school. Having covered this, we’ll rank every SHH with a rubric even us mortal folk can understand.

1. Marry- How much do the super-human exploits of the SHH make you want to: grant them an invited review; cuddle next to them at a conference; or give them shit-loads of money for a speculative start-up that you’d question more, but you’re too stupid to care or know any better?

2. Fuck- We can’t all be Alphas, and sometimes the SHH elicits our base-st emotions. You would write your own grants or run your own experiments, if only the SHH didn’t make you so god-damned horny every time they spoke, wrote or had some flatulence.

3. Kill- If you can’t screw your way up the ladder, you might as well be the murderous Beta. You’re good at what you do, but can never get positive reviews. Your burn-rate sucks and Series C financing is only going to come when Jesus himself returns.  You’re bad, the SHH is better, and it makes you hungry for blood. 

Our first SHH post will introduce us to a person who would make our comparatively miserable, listless lives in science last an unbearable eternity:

David Sinclair

Lucky for us, David has a lovely Wikipedia entry. We think he made it himself, but hey, you tried too and couldn’t keep it alive long, could you?  Wiki-living is as sure a proof as any of long-lived-ness, and David knows best here. He’s the wickedly young head of the The Paul F. Glenn Laboratories at Harvard.  We find their website a little too Glenn-y for our tastes, but hey, we’re poor and stupid, so who cares?  Also, David’s a founding member of Sirtris Pharmaceuticals, which, with its piddling public market cap at ~$300 million, means David should buy you drinks if you see him at the bar. And my, will you see him at the bar.  David simply can’t get enough of this resveratrol stuff, which may or may not make you live forever. Unfortunately, our sources tell us that David’s nose for wine is middling at best…so he’s renown for eating grams of the wine extract in a synthesized form on a daily basis.  Seeing that Sitris’s clinical trials are being conducted in India, the Pasigraph is holding out on recommending the same route for you.  Sadly, however, your life isn’t worth prolonging, at least in comparison to David.  Having discovered STACs only a few years ago, he’s roiled investors in the Boston area and reportedly gotten former advisor Lenny Guarente to recently flip from Elixir to Sirtris after some convoluted non-compete minefields. Personally, some members of the Pasigraph were raised on homeopathic cures, so we’re all waiting carefully for this xenohormesis junk to truly pan out. Regardless, David’s boundless energy and singular style make him our very first Sonic Hedgehog.

And now, the MFK honors for our fine Dr. Sinclair:

1. Marry (40%)- David is positively breaking everyone’s spirit with thoughtful and precise articles that may really prove durable in the literature. Unfortunately, he was also remembered for mailing self-addressed envelopes containing his ideas during his post-doc. When another lab member would utter derivative thoughts, David would hand them the post-marked letter from a stack, to prove to the peons how mind-numbingly stupid they (and the rest of us) really are.

2. Fuck (20%)- David is loaded, and should any good news drop in India, this category will doubtlessly grow.  Sadly, David will not, and his recent mediocre performance on Charlie Rose diminished our lust. Not to worry, Dave, the combined power of Charlie’s yapping and the Boston backdrop would leave most anyone grasping for words (we’re talking to you, George Daley).

3. Kill (40%)- There are surely folks David has stepped over and knee-capped during his meteoric rise. Maybe they haven’t lived long enough to tell. While life is high-on-the-hog now, the Pasigraph is pricing in several factors in our high “kill” ranking. First, he’s just too fucking good…and that can only mean the inevitable rise of playa-haters. Putting he and Chris Westphal in one room only burns-in the pains of our intellectual limitations. This duo is scary good and Westphal delivers babies on foreign sidewalks. Second, any ill winds from India could blow Sirtris out, and we’re always concerned about the freakiness of sour-shareholders. Should resveratrol prove itself, though, David will have been dosing himself for years, and then we’ll all have to clamor together to attempt to kill this invincible Gulliver before he crushes us with his time-less beast hands, which will prove to be the only noticeable side-effect of living forever.

Kudos, David, for being our first Sonic Hedgehog. Coincidentally, we’re drunk on wine as we write this, you tricky bastard. 

Since we bitch and moan so much here, you’re probably wondering what the hell we do enjoy.  Well, we’re gonna let you know every so often.  Here, we give you the excellence, candor and (depressing) insightfulness of Sherwin Nuland.

We won’t say much, other than that his daughter is a real slouch who serves as the current US Ambassador to NATO.  Having moved beyond that failure, Nuland went on to publish something like 12 well-selling books, countless magazine articles, all the while patching up countless hearts at Yale Med. While his own spirit is probably too great for such sniping, we’ll do him the favor of saying that Atul Gawande and Mehmet Oz only wish they had this guy’s mojo. Also, we almost wish the ex-wife he mentions in this video lived a less-than-awesome life after she drove him nuts. Almost…but Shep would have to give us permission, first. Additionally, for those intrigued by his words, the fine Dr. Nuland will be publishing his newest book soon.  We’ll be waiting at Borders with baited (Seattle’s Best) breath.

See the fat rat? It works for Cell

So, in an earlier post, we made the mistake of giving the benefit of the doubt to your average academic mega-journals. We coulda sworn they wanted readers to participate in making their brands snowy-white and super awesome. But no, as always, we here are wrong and look like assholes.

You see, as we were just about to BOMB on a paper in their comments section, we found out that, lo-and-behold, even fucking COMMENTS on Cell are subject to editorial scrutiny and cannot be anonymous! This seems even stranger when you consider that referees for the journal enjoy the very unique privileges of light editorial scrutiny and nameless, faceless back-room dealing!

This behavior is typical of the preening self-conscious folks who run such shops. We’re not wholly surprised, considering the percentage of them who couldn’t be real scientists, and would rather chat about it.

Thanks, Cell Editors. Very brave of you to feign letting two-nanoseconds of self-doubt and ulterior scrutiny invade your cushy world.  Instead, you’ve again exposed the fact you’d rather make funny mp3-type things for the Interwebs and run a journal whose editorial excellence is on par with those magazines where we can see funny pictures of Lindsay Lohan’s sagging ass.

For such profiles in courage, we here at Pasigraphy are giving out our first moniker, which we encourage you all to use in lunch chats.  Noting the general decline in quality suffered at the Cell family, their daughter journals which spread like pestilence, and the rat-like behaviors noted above, we nominate a new species to E.O. Wilson’s Encyclopedia of Life:

Cell-arsDwellars

This species can be observed in its natural habitat: a Midwest bar at a middling scientific conference, handing out favors to uber-PIs who say big words and buy them cocktails. We’ll see how long that impact factor of theirs can remain outside the Cell-arsDwellars other favorite roost: the basement.

Lastly, check back here soon. We’ll be positively RIPPING on the editorial discretion exercised by Cell-arsDwellars and their verminous brethren.

 We want to keep everyone up-to-date on moving and shaking that goes on in the scientific world…but we’d be lame if we just re-posted faculty openings from Naturejobs or executive beheadings from the FT or WSJ. So, we need YOU to tip off the Pasigraph when you just know someone’s about to fall on their face, or get elevated to a position they simply don’t deserve. We know you’re working too hard to not revel in the failures of others while raising your fist against the assholes who TOOK YOUR SPOT. Keep us in the loop, and keep checking this page.

As we all know, conferences comprise a meat-and-potatoes aspect of how everything gets run behind-the-scenes in our personal Oz. In a dark corner of the seedy bar is a PI who’s going to scoop your ass by chatting up the editor over too many gin-and-tonics. In the ball-room late at night is that hot postdoc you thought was perfectly brilliant and just “with-it”…until he started dancing/singing karaoke. Then, there’s the grad student who doesn’t know how to pace themselves, and alternates between death-staring the poster session and running to the bathroom to puke up last night’s mistakes. And finally, there’s those hotel rooms…ah, the beautiful hotel rooms. How many scientific power couplings end and start in the hotel rooms at a scientific conference?

So, we’re here and waiting.  Send us everything you see and hear, and we’ll probably post it. The more trouble someone gets in, the better. Let’s lift the scrim on a time-less affair in science…the boozy, sexy and boring (if you’re sober) scientific conference.

So, the Interweb is a pretty haughty place; Christ, you’re reading our blog. That said, we wish academic journals would leave the bragging and self-analysis to people like Chris Crocker and all those folks on Twitter. But no, Cell Press, in a typical sign of the flagging and flailing life of their brand, introduces us to the perfectly ridiculous “PaperClips” feature.

 In short, after you’ve fought tooth-and-nail to get into an exclusive lab run by a “star” investigator, you not only gain their privileged access to journal editors…you get to work 70 hours a week so your advisor hang out with the editors for a few minutes after your manuscript gets accepted with minimal revisions and discuss how beautiful and insightful your advisor is! On top of that, Web2.0 records it all and broadcasts it to the UNIVERSE! Hooray, maybe Cell will make a podcast so the hiring committee for the faculty position you’re applying to can listen to your advisor’s brilliance while riding the bus to work!

 Seriously, of all the things a struggling publishing house needs to focus on, it’s not web-y interactive features and self-congratulatory pats on the back. If you’re loosing readers and lowering your impact factor…you’ve got to solicit and publish better content.  We give three cheers to the taller-than-average kids who get to publish in Cell, but we don’t want to attend your advisor’s birthday party and don’t want to hear them talk about their Christmas presents. Here’s to letting content be king.

 (Finally, we especially enjoyed how Boston-area investigators endured the same painful teleconference as suckers from the West Coast.  Personally, we liked those days when Ben Lewin just walked over to your office with your reviews, and didn’t make a fuss of it. Nice attempt at faux Cantabrigian neutrality, Cell-ers!)

 Please pass on any similarly displeasing moments of journal-y incestuousness.