media frenzy!!!

Self-explanatory.

1. RadioLab's Desperately Seeking Symmetry

Jad and Robert probe the benefits of symmetry, and asymmetry.


2. Chris Brown's 'Look at Me Now'

I don't love supporting domestic abusers, but I do love Busta Rhymes and Lil' Wayne. And disco ball faces.


3. Lil Wayne's '6 foot 7 foot'

Nothing like watching Weezy's brain go flying. I also love the "death is her sister" part. And of course the whole 'Inception' reference (is it a reference if it doesn't make any sense?)


4. Karmin!
I can't seem to embed their videos, so just go to their YouTube channel and watch their covers of 'forget you', 'look at me now', 'whip my hair', 'born this way', 'hold it against me,' just for starters.

filariae and force generators

I won’t lie; being the geeked-out loser that I am, I love reading about modern science. I’m often most impressed by advances in technology when I see the depths we’re able to probe into the origins of biological processes. Yet, the excitement I get from reading about novel therapeutics or mechanistic insights of the modern era is often dwarfed by how I feel when I read about seminal studies that laid the foundation for modern wizardry with barely a fraction of the tools. Two examples follow.

William Withering and the Foxglove
A terrific paper published last week in Science discusses the discovery and implementation of a new drug, omecamtiv mecarbil, for systolic heart failure. Basically, the authors started by revisiting the function of cardiac myocytes. Like any muscle fiber, cardiac muscle contracts via a cooperative actin-myosin system, for which myosin is the key. The myosin heavy chain has a head with two critical components: an ATP-hydrolyzing domain, and an actin-binding site. It also has a spring-like neck which allows for force transduction. The process by which myosin coordinates muscle contraction is actually quite interesting. In its “resting” state, myosin is bound to ATP; the ATP-bound myosin has very weak catalytic activity which will, over time, lead to slow hydrolysis and consumption of ATP. When a muscle is stimulated, release of acetylcholine at the neuromuscular endplate leads to activation of g-protein coupled receptors which, via increase of intracellular cAMP, leads to release of calcium from the sarcoplasmic reticulum. Calcium then binds to troponin C and tropomyosin, which release the actin-interacting region of the myosin head to bind actin. This event is critical, as actin-bound myosin has a higher rate of ATP hydrolysis; subsequenthydrolysis and release of inorganic phosphage by actin-bound myosin leads to the classic shortening of the myosin neck and the so-called “power stroke”, causing shortening of the sarcomere. In parallel, many of these shortenings lead to muscle contraction. Now, the key here is that this is a high-energy process (as anyone who exercises can tell you) but the majority of energy consumption comes not from the ATP hydrolysis by myosin but by the energy required to actively transport calcium back into the sarcoplasmic reticulum. The other key aspect of this process is that the rate-limiting step in contraction is the transition from weak (ATP-bound)actomyosin interaction to strong (ADP bound) actomyosin interaction → the rate of this step is limited by the rate of actin-bound ATP hydrolysis.

We’ll get back to this story in a second, but lets digress and talk briefly about heart failure. Systolic heart failure, in which the primary defect is in the contractility of the heart, is the dominant form of heart failure in the US (unlike in, for example, Africa, where diastolic heart failure appears to dominate). Improving contractility in heart failure takes two forms: optimizing conditions for cardiomyocyte contraction, and improving intrinsic cardiomyocyte function. By optimizing conditions for contraction we mean a) preload optimization to optimize starling forces (this is where beta-blockers are most useful) and b) afterload reduction to improve contractility (this is where ACE inhibitors and spironolactone appear to be most useful). There is a third aspect, diminishing pathologic cardiac fibrosis, in which both ACE inhibitors and spironolactone appear to be useful.

Improving intrinsic contractility is more difficult. The only drug that is thought to achieve this in an outpatient setting is digoxin. Which brings us to (drum roll) William Withering. Who was he? Well, he was born in 1741 in England, the son of a successful apothecary. He studied medicine at the University of Edinburgh where he had a particular interest in a syndrome known as “dropsy” (short for hydropsy, an old term for edema). He ultimately took up practice in the local village of Stratford, where, due to the interest of his new wife, an artists who specialized in botanical arrangements, he became interested in botany. In order to supplement his income, he moved in 1775 to Birmingham and became a member of the famous “Lunar Society” (a group of high-minded people who met at the monthly full moon and whose members included Charles Darwin’s grandfather, the discoverer of oxygen, the inventor of the steam engine, and Benjamin Franklin). Withering’s story becomes relevant to this scatterbrained post in 1775, when he becomes alerted to a familyremedy for dropsy: an herbal tea made from the leaves of the English foxglove plant, the active ingredient of which was digitalis.

It is important to note that Withering did not discover digitalis; indeed, it had been used since the 1200s for a variety of conditions. However,Withering’s unique skillset as a physician and botanist allowed him to study the effects of foxglove and report, in a landmark book, An Account of the Foxglove, a careful summary of 163 case studies over the course of a decade. In the book, he describes the preparation and administration of the drug, as well as a highly accurate description of digitalis toxicity (including overdiuresis, GI irritation, visual changes, and life threatening bradycardias and bradyarrhythmias). He then offers advice for therapeutic administration of digitalis, which, to this day, remains the only outpatient drug known to improve cardiac contractility.

And, that brings us back to the current day. Digoxin is obviously not the only drug that improves contractility; in the hospital (specifically, in the ICU), drugs known as inotropes are used to augment cardiac output. Chief among these drugs are dobutamine (a beta-1 receptor agonist) and milrinone (a phosphodiesterase 3 inhibitor). Both act ultimately by increasing intracellular levels of cyclic AMP, which increase calcium levels and therefore augment contractility. However, there are three major problems with use of these drugs.

• Both drugs act peripherally as well as centrally, causing peripheral vasodilation. In patients with cardiogenic shock, this can cause life-threatening hypotension
• Both drugs act by increasing intracellular calcium; because this is the primary avenue of ATP consumption in the cardiomyocyte, these drugs significantly increase myocardial oxygen consumption, which is a big problem in patients who have cardiogenic shock secondary to an ischemic event (like a myocardial infarction)
• Both drugs are highly arrhythmogenic for multiple reasons (they cause electrolyte abnormalities as well as tachycardia).

So these drugs are a problem (and the side effects are probably why use of these drugs has never had a proven mortality benefit). So we come back to our brilliant authors, who looked at the normal cycle of actomyosin contraction and realized that there was another area that could improve contractility. What if there were a drug which acted to speed up the rate-limiting step of contraction (ATP hydrolysis by the myosin head)? Better yet, what if this drug increased the rate of ATP hydrolysis by the myosin head only when it was bound to actin, therefore improving the efficiency of actomyosin interaction?

Well, that’s exactly what their drug, the inexplicably named omecamtiv mecarbil, does – it’s a cardiac myosin-specific ATPase agonist which preferentially acts when myosin is actin-bound. The drug clearly increases sarcomere shortening without changing the amount of intracellular calcium elevation (pictured); the net effect is a significant increase in stroke volume while sparing any effects on the heart rate and a net increase in cardiac output. So what are the problems with this drug? Well, there’s one main problem: because the drug potentiates ATP hydrolysis, it lengthens the amount of time that myosin interacts with actin. The net effect of this is that it increases the amount of time that the heart is in systole. Sounds good, but the problem is that coronary artery filling happens during diastole (when the coronary arteries aren’t compressed). So the dose is limited by myocardial ischemia from impaired diastolic filling. Still, this is an orally bioavailable drug which means that it may be valuable for patients with heart failure in both an inpatient and outpatient setting.

On to the next!

Worms.
So, filiariasis (infection by the thread-like filarial roundworms) is pretty gross. The key to their causing repulsive conditions like elephantiasis (where they obstruct the lymphatic system), disseminated rashes and urticaria, so-called “river blindness” (where one filiarial worm infects the eyes), and even serous cavity filariasis (where they occupy the peritoneal cavity) is their ability to disseminate while avoiding recognition by the immune response.

So scientists have been interested in how, exactly, they accomplish this stealth process for quite a long time. And in 1980, in a paper published in the New England Journal of Medicine, they pretty much figure it all out, with the use of some primitive tools. They isolated peripheral blood white blood cells from adult volunteers in Indonesia with recurrent lymphadenitis characteristic of filiariasis. They would then stimulate white blood cell isolates with either filarial antigens or, as a control, tuberculosis antigens, and compare the growth of stimulated to non-stimulated cultures (which they termed “stimulation index.”)

Their results, with these simple assays, were remarkable. To start, the authors found that peripheral cells from patients had no response to either TB or filarial antigens. However, when they depleted adherent cells from the peripheral cultures, responses to filarial antigens spiked (indicating that adherent cells were specifically suppressing anti-filarial responses).Additionally, if they delayed antigen exposure overnight before stimulating the peripheral cells, responses to filarial antigens also increased, suggesting that adherent cells are continuously suppressing anti-filarial responses in an antigen-dependent manner.

Finally, they found that supernatants from patients with filariasis suppressed both antifilarial and, to a lesser extent, anti-TB responses, suggesting that suppression by adherent cells occurred via secretion of soluble factors. All this, just by looking at cell counts!

In the years following, studies of the filarial nematode Acanthocheilnema vitae yielded a protein, ES-62, which was found to have numerous suppressive effects on the immune system. Notably, it was found to block macrophage production of Th1-type cytokines (sound familiar?) leading to preferential Th2 differentiation of T cells and suppressing T cell proliferation. It was also found to be clinically useful in the treatment of inflammatory arthritis and allergic asthma by suppressing macrophages and mast cells. In last week’s Nature Immunology, the authors found that recombinant ES-62 suppresses systemic inflammation induced by both TLR4 and TLR2 (2 innate immune receptors highly upregulated on macrophages and neutrophils during sepsis) by inducing ubiquitin-mediated degradation of TLR4 and the critical adaptor protein MyD88.

They then demonstrated that in a well-known mouse model of sepsis in which the cecum is ligated to serve as a nidus for infection, then punctured to release bacteria into the bloodstream, ES-62 can not only prevent sepsis but also treat it if administered within 6 hours of bacteremia while at the same time not interfering with clearance of bacteria from the peritoneum or bloodstream. Now don’t get me wrong; the ability to take those initial findings, isolate the protein responsible, and demonstrate its potential therapeutic efficacy is terrific. But the critical findings: that adherent peripheral blood cells produce a soluble factor in response to filarial antigens that effectively suppresses the adaptive immune response, were known over thirty years ago, and were discovered with little more than some volunteers, a centrifuge, an incubator, and a microscope.

Omecamtiv mecarbil! Acanthocheilonema viteae!!!!

"Enough of this pop culture nonsense!" screams the massive imaginary readership. "We demand a return to esoteric science!"

Your fury is heard, non-existent mob of science lovers! Stay tuned...

follow-up

First, I suppose I should note that the genesis of that giant word vomit was an ongoing, approximately four year-long discussion that my friend Todd and I have had about the merits of Mr. Timberlake following a night where Todd's feelings on the subject were clarified while watching an HBO special of his performance. I should also note that this clarity may have been chemically aided. But I digress.

I feel that I should offer a little bit of (still unsolicited) clarification to the imaginary people who are up at arms about my previous post. It’s possible that because I had such an obviously good time deconstructing the myth of JT’s artistic supremacy that my post appears to be primarily about how I hate him. But that’s really not the point – I don’t hate him at all (as many people who have heard me give poor renditions of “Senorita” can attest). It’s more about how enticing it is to buy into established narratives. Somewhere along the line we decided that Justin and Gaga are “artists” whereas Britney is a “product.” Because of that, we view all of their activity through those filters: Gaga imitating Madonna is an homage, and songs like Telephone are satire, whereas Britney performing Like a Virgin is marketing. I just think that with prominent pop culture figures like these particular people, for whom their imposed narrative seems far more dominant than their reality, that its interesting to re-examine their careers.

The other obvious criticism is that JT and Gaga are established musicians – they are both extremely talented singers and musicians, whereas Britney Spears clearly is not. I completely agree (see Gaga’s VMA performance of Paparazzi or JT’s SNL performance of Senorita if you need proof). One might even argue in the case of JT that he has not attempted to consciously manipulate his public image, instead allowing his musical product to speak for him. To that I would say 2 things. First, I think its reasonable – I just think it’s a double standard to view Gaga’s control of her image as clever and Britney’s as fake. And second, JT’s decision to allow his music (whenever he makes it) to speak for him is commendable – it just makes him less relevant. It reminds me of Nirvana and Pearl Jam. Both emerged out of Seattle, both were relatively counter-culture (especially compared to Michael Jackson), but unlike Pearl Jam, Kurt Cobain was extremely aware that Nirvana had cultural resonance beyond the simple quality of their music (which is why he wrote “Smells Like Teen Spirit” and agonized over making In Utero sound ugly – Klosterman’s article on this is genius). As a result, Pearl Jam might well have had better musicians, but Nirvana was far more important. And that’s how I feel about JT and Britney.

I will also add that, whatever my feelings about his musical legacy are, there's one thing that can't be doubted about JT, and that's his SNL hosting legacy - he is awesome on that show.

relevance

I’m returning from a lengthy hiatus to urgently discuss a matter of significant importance (to my sanity). So.

I’ve always been a big music fan; when I was young it was simply a matter of what music I liked listening to (as a kid, Michael Jackson, as a teenager, Nirvana and Nine Inch Nails). As I got a little older, as all teenagers who like to wax poetic about art do, I started becoming interested in characterizations of artists in terms of their broader cultural significance. This topic was more interesting with regards to conventional ‘popular’ (pop) artists, in large part because pop artists’ significance seemed to be determined as much by their ability to influence the cultural landscape as by the intrinsic quality of their music. This was in contrast, at least somewhat, to

the more meritocracy-based popularity of rock and hip-hop artists (just allow me to stipulate that argument, we can debate it at another time.)

It’s not surprising that arguments over which pop artists were most relevant were more heated when I was a kid. Two reasons come immediately to mind: first, the lack of broad access to media (aka, the lack of the internet) decreased competition for the attention of fans, and second, … well, the artists in question were just much better. Feuding for control of the pop culture landscape in the mid 80s and 90s were Michael Jackson, Madonna, and Prince. We then went through a period of counter-culture in which alternative music became mainstream before re-emergence of classical pop music in the late 90s with the growth of so-called bubble-gum pop. Two of the primary characters in this new emergence were, of course, Britney Spears and Justin Timberlake.

The notable events in the biography of Timberlake and Spears are fairly common knowledge to anyone in high school or college during this era: their parallel early success, their high-profile, yet strangely boring and unrealistically serious relationship, and their inevitable breakup rife with accusations of infidelity. In the aftermath, Timberlake’s blistering single “Cry Me a River” was the genesis of an emerging narrative in which Spears’ success was determined to be a product of her ruthless ambition and to be in spite of her artistic vacuity, while Timberlake was cast as the earnest poet. The hero and villain(ess) in this story were obvious. Over the following years, each character did their best to advance the narrative with which they had been supplied; JT ascended to pop royalty, producing two fairly popular and critically acclaimed albums, while Spears married and divorced a guy who wrote “Popo Zao,” had two children, shaved her head, and generally became a lunatic. When Spears quietly re-emerged with 2009’s Circus, 2010’s “3,” and 2011’s Femme Fatale, while JT continued to be musically silent, this narrative remained curiously unchanged; JT continued to be considered one of popular music’s 2 culturally transcendent artists (along with Lady Gaga), while Spears’ success continued to be cast as outside of the realm of cultural significance.

Well, I plan on reassessing these myths, despite the fact that no one really asked. Let’s take a trip down memory lane, shall we?

Early Careers (late 90s to early 00s)

Now, most would consider the early careers of Timberlake and Spears to be a wash; Spears was the face of a production team that generated largely forgettable hits, while Timberlake was the face of a boy band that was the face of the same production team generating yet more forgettable hits. And while that may be mostly true, I think a few points are worth noting:

• Spears’ job was ostensibly tougher as a solo artist, attemping to win the favor of an emerging target audience (young teenage girls) who generally tended to favor male artists. Despite this, Spears’ freshman album effort, …Baby One More Time, and its title single were far more culturally resonant than the summation of *NSYNC’s entire catalog. It’s further worth noting that the driving force of the single’s notoriety (it’s controversial, Catholic schoolgirl-themed video) came from Spears herself (the label had originally suggested an animated video). This was the first suggestion that Spears was highly aware that she was able to use her status to stir up controversy.
• At the peak of her success from …Baby One More Time, Spears continued to court controversy, appearing on the cover of Rolling Stone with her shirt unbuttoned. When asked, Spears reportedly responded, “What’s the big deal? I’d do it again. I thought the pictures were fine. And I was tired of being compared to Debbie Gibson and all of this bubblegum pop all the time.” (During this time, *NSYNC did not seem the least bit uncomfortable with their sqeaky clean image, choosing to keep still waters calm with such singles as “This I Promise You,” “It’s Gonna Be Me,” and “Bye, Bye, Bye” – none of which, thank god, has had any musical permanence.)

In 2001, Spears began to experiment sonically with her sound. Apparently inspired by Jay-Z, she hired the Neptunes (who until this time had produced only modest hits such as N.O.R.E’s “Superthug,” Kelis’s “Caught Out There,” Mystikal’s “Shake Ya Ass,” and a few others) to produce the lead single from her third album, Britney. The single, “I’m a Slave 4 U” was radically different from all of her prior singles, featuring a slithering, hip-hop oriented beat; nevertheless, the single was a worldwide #1 smash (and for the record, is an awesome song, probably the Neptune’s best beat ever.) During this time, Spears also took a brief, and fairly terrible, foray into acting with 2002’s Crossroads.

JT, meanwhile, took a larger hand in the production of *NSYNC’s 2002 album, Celebrity. The album featured probably their only worthwhile song, "Gone." While none of the songs on this album matched the sonic inventiveness of "Slave 4 U", the band did interestingly take a hint from Britney and commission the Neptunes for production of their third single, “Girlfriend.” (You’ll note this theme of Spears’ going uncredited for innovative choices while JT incomprehensibly receives credit for generation of unoriginal work a few more times.)

2002 – 2004: Generation of divergent narratives

2002 in the arc of both of these stars is defined by the end of their relationship and conviction of Spears for said end. Following their breakup, rumors circulated widely suggesting infidelity by Spears during their relationship. In late 2002, JT released his first solo album, Justified. It was produced entirely by the Neptunes, who, by this time, had produced not only Spears’ “Slave 4 U” but Nelly’s “Hot in Herre” and won Producer of the Year at both the Source and Billboard Music Awards, and Timbaland, who by this time had already produced countless hits for Jay-Z (“Big Pimpin,’”), Aaliyah (“Are You That Somebody,” and Missy Elliot (“Supa Dupa Fly” and “Work It,”) amongst others. So he was really taking chances with unknown commodities. The video for the album’s second video, “Cry Me A River,” eliminated the doubts of anyone who had suffered a severe brain injury and thus did not understand the subject matter of the single (Spears’ purported infidelity.) Meanwhile, Spears’ declined to comment publicly on the end of their relationship, noting only in an interview with Chuck Klosterman that she and Timberlake “were too young to be so serious.” She did, however, co-write a song, “Everytime,” in which she pleads for forgiveness following the end of a relationship.

Justified was a successful debut album for JT (although with 3 million records sold domestically, nowhere near the success of Spears’ first 3 albums, with 26, 20, and 12 million albums sold respectively). The album’s relatively diminished commercial success was compensated by its critical acclaim; the album received strong reviews, and “Cry Me A River” was its biggest hit; Timberlake was rewarded for exploiting his private relationship for public gain, while Spears was vilified for her silence on the issue. But this growing narrative failed to account for one minor point:

Justified sucks. OK, well, it doesn’t suck; it’s a perfectly decent album with a few catchy songs (though not nearly as many as any of Spears’ or NSYNC’s prior albums). Rather, the canonization of Justified as an artistically sound album is just categorical nonsense. First, its mind-bogglingly unoriginal in its near-total reliance on production by the Neptunes and Timbaland, the 2 most popular producers in the world at that time. Lyrically, the album is a joke, featuring 11 songs that express the topic of Timberlake’s excellence as a lover and 2 songs that bemoan how he has been unfairly wronged. To this day, I cannot understand how Timberlake was actually lauded for “Cry Me a River,” in which he very publicly aired the dirty laundry of his former relationship – a man, who bears no pressure of fidelity in popular culture, publicly questions the morals of his ex-girlfriend (who, as a woman, is constantly held unfairly to a standard of virtue that he is not), and we celebrate him for it? Unreal. Oh, I almost forgot. Justified also includes one song, “Rock Your Body,” in which he educates us that not only is he terrific in bed, but that smoking weed is awesome. Thanks, guy.

Spears, meanwhile, followed her newfound notoriety with 2003’s In the Zone, in which she also took an artistic step forward by co-writing and co-producing nearly all of the tracks. Unlike Timberlake, Spears shunned high-profile producers, opting instead to work with unknown producers such as the Matrix, Bloodshy & Avant, and Redzone, as well as non-pop producers such as Moby. These choices marked Spears’ desire for the album to reflect her changing musical tastes; the album appropriately features more club-oriented music. Spears was aware of the commercial sacrifice of pursuing her individualism, saying, “Of course I’m not doing ‘Baby One More Time’ and those massive hits anymore. I think this record is where I am at right now in my life.” The album’s first single, “Me Against the Music,” was originally a solo track, but was re-envisioned by Spears’ as a duet after she played the track for Madonna, who expressed her interest. The album’s second single, “Toxic,” was one of Spears’ biggest hits (and probably the most interesting song in her catalog); despite its production by an unknown producers, it far outclasses any song off of Justified. Lyrically, the album was Spears’ most autobiographical, and featured Spears’ emergence as a single woman (note the much more interesting topics of “Early Mornin’” (hangovers) and “Touch of My Hand” (duh)). The album’s only reflection on the past, the aforementioned “Everytime,” was as understated as Timberlake’s was grotesquely public (Spears’ music video for Everytime showcased her growing anxiety with the paparazzi, a concept that, I suppose, is far less creative than dancing around a Britney Spears imitator – I imagine those were pretty hard to find.) In the Zone outsold Justified domestically and internationally by almost threefold, and like Justified, was awarded with a Grammy (best dance recording for “Toxic”), yet was considered to be a relative failure.

2004 – 2008: Canonization of a myth

I will be the last to deny that from 2004-7 Spears really helped further the public perception that she was a hack, marrying the decorticate Kevin Federline, having 2 kids, divorcing Federline, shaving her head, showing her hoo-hah getting out of limos with Paris Hilton, and finally checking into a rehab center in late 2007 (although, why any of these behaviors diminished her validity as an artist is not entirely clear to me - don't we regularly glorify male celebrities for this sort of excess?). The net effect of all this behavior, occurring during a vacuum in which Spears released no music, was that her notoriety for non-artist behavior far outmeasured her artistic output (of which there was none).

On the other hand, lets consider young Timberlake’s monumental accomplishments during this time. It begins in 2004, where Timberlake gave us his most forgivable act of these 4 years: briefly showing Janet Jackson’s boob during the Super Bowl. Good for him. Of course, this led to years of unnecessary TV censorship and apparently some sort of mandate that everyone who performs at the Super Bowl has to be old enough to have an enlarged prostate; thus, 2005’s Paul McCartney, 2006’s the Rolling Stones, 2008’s Tom Petty, 2009’s Bruce Springsteen, and 2010’s the Who. Meanwhile, Janet Jackson’s career began a slow descent following the infamous ‘warddrobe malfunction’ (her subsequent albums Damita Jo, 20 Y.O., and Discipline were all commercial failures) while Timberlake escaped unscathed, despite the fact that he was the one who ripped her bra cup off in the first place (by all accounts, the whole stunt was his idea). Unbelievable.

I suppose this incident was so scarring to JT that he put his fledgling music career on hold to make as many movies that are worse than Crossroads as possible, playing bit parts in Edison Force, Alpha Dog, Black Snake Moan, and Southland Tales. I have actually seen one of those movies – how many people can say the same?

All of this nonsense, however, was apparently forgiven with the release of Timberlake’s sophomore effort, the hilariously titled Futuresex/Lovesounds. The album won Timberlake significant acclaim, despite the fact that, from the title, I can only assume that JT has some closeted fetish for robot pornography or something. Nevertheless, FSLS is not without its merits (See? I’m not an unequivocal hater!) Sonically, despite being produced entirely by Timbaland, who proved how important Timberlake was to this process by being equally responsible for the success of Nelly Furtado’s Loose as well as his own album, Shock Value, JT’s second album is far more interesting than his first. While the first single, “SexyBack,” which features a boast, that he is “bringing sexy back,” made many of us wonder whether he actually understands what a noun is, I was impressed by the song’s unconventional melody and structure. The album featured a number of other interesting bits of music; however, these were mostly in the interludes between songs (“Let Me Talk To You,” “I Think She Knows”). These interludes were reportedly the result of Timberlake’s broadening musical interest (the band Interpol reportedly being the inspiration for “I Think She Knows”) – yet in stark contrast to Spears, Timberlake was unwilling to risk his commercial success by featuring his interests, and thus relegated them to hidden interludes at the end of featured tracks. Oh yeah – the album has a track, “Losing My Way,” in which Timberlake pretends to be a middle-aged blue-collar male who has become addicted to crack. I find this to be one of the stupidest songs ever written. Nevertheless, FSLS was Timberlake’s biggest hit, selling 14 million copies worldwide and 4 million domestically.

In late 2007, Spears released her fifth solo album, Blackout, quietly and notably without promotion from her label, Jive Records (which was angered by the online leaks of tracks from the album before its official release). The album, which reflected Spears’ continuing interested in club culture and music, was perhaps her most critically acclaimed, winning Album of the Year at the MTV Europe Music Awards in 2008 and named the most influential pop album of the past five years by Rolling Stone in 2011. However, as the Guardian noted, “It’s a bold, exciting album; the question is whether anyone will be able to hear its contents over the deafening roar of tittle-tattle.” Undoubtedly, Spears’ attempted comeback was premature as evidenced by her discombobulated and critically panned performance of “Gimme More” (an admittedly awful song) at the MTV VMAs in 2007. However, even on this album, Spears’ showed us an ability for self-awareness that JT seems to be conspicuously lacking with her second single, “Piece of Me,” in which she announces herself as “Mrs. Oh my God that Britney’s shameless.” “Piece of Me” served as the true jumping off point for Spears’ resurgence.

2008 – The Return

It’s pretty easy to summarize Timberlake’s activity since 2006’s FSLS, because there isn’t much. He collaborated with Madonna on 2007’s hideous “4 Minutes” (did I mention Madonna collaborations before?) also contributing 4 other tracks to her album, Hard Candy, which competes strongly with American Life as her worst album. Apparently content with one forgettable album and one decent one, Timberlake resumed his acting “career” with 2008’s The Love Guru. That’s right: The Love Guru. With Mike Myers. Remember that movie? He also because a sort-of cast member on SNL, hosting three times and featured in multiple other guest appearances. His collaborations with Andy Samberg produced “Dick in a Box” and “Motherlover,” which were both unequivocally awesome. He appeared in 2010’s terrific The Social Network, in which he used his finely honed theatrical craft to play Sean Parker – a famous young white man who enjoys going to clubs and hooking up with women. In 2011, he will appear in Friends with Benefits with Mila Kunis, a movie to whose awfulness I can do no justice, so I’ll simply link to the trailer.

Meanwhile, following 2007’s abominable performance of “Gimme More,” Spears was involuntarily hospitalized at Ronald Reagen UCLA Medical Center in early 2008. However, following her release, she appeared in How I Met Your Mother as Abby, a socially awkward receptionist trying to win the heart of Ted (one of the main characters). She was critically lauded (and I have to say, pretty funny) and later reprised her role in a subsequent episode. She then filmed and released a documentary, “Britney: For the Record” chronicling her efforts to regain her former prominence; the documentary garnered MTV’s highest ever ratings in the timeslot in which it aired. At the same time, the aforementioned “Piece of Me” won video of the year at 2008’s VMAs. This combination of events paved the way for Spears to renew public interest in her as an artist (as opposed to as a headline on a Perez Hilton website).

Her sixth studio album, Circus, did just that, returning her to critical and commercial prominence by way of her first number 1 single, “Womanizer,” since …Baby One More time. Spears continued to depart from her former squeaky-clean image and poked fun at her love-hate media relationship with the follow-up smash hit, “If You Seek Amy.” This return to prominence was rewarded by a matching resurgence in public appreciation/fandom as marked by her massively successful Circus: featuring Britney Spears tour.

Spears followed Circus in 2009 with a compilation, The Singles Collection. This featured Spears’ second consecutive number one hit, “3,” which met the notable challenge of writing a hit single about threesomes. Not content with this success, Spears released her seventh studio album, Femme Fatale, featuring two consecutive number 1 smashes, the mediocre “Hold It Against Me” and the frankly awesome “Till the World Ends.” Femme Fatale is yet another mark of Spears’ desire to express her personal musical evolution, as the album features a number of tracks written in dubstep, a dance music style popularized in clubs in South East London.

So. How can we summarize all of this?

On one hand we have JT, an immensely talented singer and songwriter, who helped produce a series of largely unmemorable, conservative hits for *NSYNC, forayed into solo artistry in the most safe way possible, using the most popular producers of his time while exploiting his recently ended relationship to further his reputation, took a brief hiatus to make a bunch of terrible films, made one pretty good album, made another bunch of terrible films, 2 funny songs with Andy Samberg, and did a reasonably good job in the Social Network.

On the other hand, we have Spears, a solo female artist who produced three monumentally successful commercial albums (with significant evidence that she was the driving force, both sonically and artistically, behind a number of critical elements responsible for her success), refused to respond to her public denigration following her breakup, began an artistic departure that reflected her shifting musical tastes at the expense of her commercial success, went crazy, married a loser, had 2 kids, divorced said loser, released 1 critically acclaimed but commercially unsuccessful album, went into hiding for about a year, and re-emerged to completely shed the coattails of her former success and reinvent herself as a club-busting hitmaker with her sixth and seventh riotously successful albums. In doing so, she’s summarily dispatched of many of her so-called competitors (remember how willing we were to call Christina Aguilera the artistic yin to Britney’s yang? We were all pretty quiet when after 2006’s Back to Basics, Aguilera’s attempt to reflect her personal tastes, flopped, her transparently pathetic attempt to regain pop success with 2010’s Bionic was thankfully forgotten).

Meanwhile, Lady Gaga has supplanted Spears as Madonna’s heir apparent (partially because of Britney’s embracing of slightly left of mainstream club culture, and partially because Gaga is obsessed with cultural relevance), yet despite her awesomeness (and don’t get me wrong: Gaga is as flat-out awesome as they come), her completely transparent aping of Madonna (her machine gun bras, her new single which can literally be superimposed with Madonna’s “Express Yourself”) has not even remotely tainted her artistic credibility. And I don’t dispute that; really, I don’t. But we shouldn’t forget that Gaga’s true rival for lasting cultural impact this decade isn’t Katy Perry, or Rihanna. It’s Britney.

(sigh, fine) Bitch.