This carboxyl group sometimes causes problems...

On October 3, 1999 Fox broadcast an episode of The Simpsons entitled Brothers Little Helper that contained probably the most accurate representation of medicinal chemistry ever portrayed on a network television cartoon series.  That is to say, there were two lab-coated scientists with some vaguely chemical-ish knowledge who gave some drugs to Bart to treat his ADD.  It was a proud 22 minutes (30 minutes with commercials) for those of us in the field.

It's a funny episode, too.  In summary, Bart behaves badly.  Principal Skinner demands he go on an untested experimental ADD drug called Focusyn created by a company called The Pharm Team as a condition of continued enrollment at Springfield Elementary.  After Marge's guilt-trip, Bart accedes to taking the drug.  At first it appears to work.  Maybe a little too well.  Bart becomes focused to a fine point.  He starts to behave like a Type A motivational speaker or life coach.  But a little later, he goes off the rails.  He gets paranoid and starts claiming that Major League Baseball is spying on everyone via satellite in order to collect their personal data, especially their buying habits and hats sizes.  Eventually, Bart runs off to an army base, steals a tank, and uses it to shoot down the offending MLB satellite.  As the town discovers that Bart's paranoid claims were actually true, Mark McGwire shows up in a helicopter and distracts everyone by "hitting a few dingers".  Bart is let off the hook for stealing the tank and shooting down the satellite, and he switches from Focusyn to Ritalin, like every other good, normal American kid.  The end.

As I said, it's funny.  But there are also subtleties in the story worth examining from a medicinal chemist's perspective.  And a baseball perspective, for that matter.

The "Chemistry" Angle
First, the science.  I won't get into the problems with Homer and Marge wandering through a functioning chemistry/biology lab without any personal protective equipment (safety glasses and lab coats to the layman).  I won't get into the dubious ethical issues surrounding the idea of giving Bart some untested drug for ADD when other perfectly reasonable approved options were available.  It's a cartoon for heaven's sake.  Dramatic license and all that.  Instead, I'm going to get semi-myopic about the chemistry.

At one point in the episode after Bart's paranoia becomes acute, the Simpson family returns to The Pharm Team headquarters to address the problem.  The female scientist-like person gestures toward a molecular model of what is presumably Focusyn and says, "this carboxyl group sometimes causes problems."  Now we're getting somewhere!  That is a sentence that could genuinely be spoken in a medicinal chemistry laboratory environment!  A carboxyl group is a real thing, and it can cause problems for drugs.  Most of these problems are associated with absorbance, metabolism, or distribution of a drug, but I'll allow for the possibility that a carboxyl group might be the key functional group responsible for causing paranoia in an ADD drug.  Why not?  Yay!  Medicinal chemistry on prime time TV!  Huzzah!  Of course, you should probably have all that stuff worked out before you start giving a drug to children, but let's not start picking nits.

Unfortunately, the molecular model doesn't possess anything that can be reasonably designated a carboxyl group.  See for yourself:

I drew this myself, by the way.  I couldn't find any screen captures of the image from the episode, so I made this one using Paint(TM).  It's a pretty accurate re-creation, I think, especially considering my incredibly poor art skills.  So let's analyze this sucker, shall we?  So...if blue is carbon, orange is nitrogen, red is oxygen...hmmm...no that's no good.  Okay, what if orange is carbon, red is nitrogen, and blue is...geez...phosphorus?  No.  Okay, the structure needs some work.  I mean, what the hell is a half red, half yellow atom supposed to be?  On the plus side, there's nothing in this structure that could reasonably be considered to be a pentavalent carbon.  Small victories, eh.

Anyway, the problematic carboxyl group leads Marge and Homer to suggest taking Bart off Focusyn cold turkey.  The male and female sciencey types express alarm at the proposition, and instead suggest Bart transition to three other drugs: chlorhexanol, phenylbutamine, and cyclobenzanone.  The first two names are dangerously close to being real chemical names.  I could propose structures for either, though I don't think I would willingly swallow any of the compounds I would propose.  The third compound is tougher.  It certainly sounds chemically, but in a sort of self-contradictory way.  Google suggests changing to cyclobenzaprine which is a real drug, a muscle relaxant that might have taken the edge off for Bart. Partial credit for that one.

So the science is not great, but it's above the bar I would set for an episode of 'The Simpsons'. So bully for the writers.

Here's where things get a little more fun. I'm sure the drug name Focusyn was meant to be a tongue-in-cheek selection chosen to make light of drug marketing.  But here's the thing, the pharmaceutical industry is certainly not above somewhat silly transparently instructional brand names.  Here are a couple of my favorites:
 1.) Anti-schizophrenia drug, aripriprazole is sold by Bristol-Myers Squibb as Abilify(R).  See, if you have schizophrenia you are not able, but aripriprazole will 'abilify' you.
2.) Tamsulosin is a treatment for enlarged prostate that's sold by Astellas as Flomax(R).  Is your urinary output disappointingly slow?  Here, take some Flomax to maximize your flow.

It gets better, though.  In November 2001, the FDA approved a drug call dexmethylphenidate for treatment of ADD.  (It's actually just the active enantiomer in Ritalin.  You see, Ritalin is sold as a racemate meaning that it actually contains two compounds that are mirror images of each other.  One is active and the other....you know what?  Skip it.  It's just important to know it's a treatment for ADD).  Novartis markets the drug under the brand name Focalin.  Yep, as in "my son has trouble paying attention in class so he takes this drug to help him focal-in."  Pretty damn close to Focusyn, don't you think?  And it hit the market after Brothers Little Helper aired.  Is Matt Groening getting royalties from Novartis for this?  He should be!  (Cute side-note:  according to the good people at wikipedia, Celgene also sells dexmethylphenidate, only under the brand name Attendade, as in, "my son needs Attendade as an aid to help him attend to his studies.")

The MLB Angle
But the most intriguing thing about Brothers Little Helper is the role MLB plays in it.  Stay with me.  We're going in deep here.

In October 1999, Mark McGwire had just completed his second consecutive season hitting over 60 home runs (70 in 1998, 65 in 1999).  His race with Sammy Sosa to break Roger Maris's 37 year-old homerun record in '98 was responsible for bringing fans back to baseball four years after a players' strike shortened a season and canceled the World Series.  So Big Mac was a certainly a good choice to come by and distract the good people of Springfield with a prodigious display of baseball blasting.  Of course, it wasn't long after their remarkable season that fans learned that McGwire and Sosa, along with many others, had been enhancing their performance chemically.  The resulting scandal and investigation trashed the reputations of many previously respected players, and MLB was forced to implement a much more stringent anti-drug policy in order to rebuild its integrity.

Brothers Little Helper aired in the middle of all this -- after the homerun record-breaking but before the scandal.  In the episode, drug use threatens MLB's profitability, but once again the long ball saves the day.  In the episode, the story is turned on its head as the outsider Bart incidentally uses a drug that gives him the perception to see MLB's scandalous behavior.  Taking it to the next level, the company that supplied Bart with the Focusyn was named The Pharm Team -- a play on the term 'farm team'.  Farm teams are responsible for preparing young ball players for the big leagues.  The Pharm Team accidentally provided young Bart with the paranoia and intellectual focus that allowed him to uncover MLB's sneakiest plot yet.  Intentionally or not, the writers once again suggest that baseball's incautious supervision of drug use nearly endangers its profitability.   I find this parallel fascinating.  It would be pretty cool if the Simpsons' writers had been that prescient, but I doubt it.  They certainly don't make indication of that kind of insight in the DVD commentary for the episode.  In the end, it's really just meant to be a mildly satirical commentary on the over-prescription of psychotropic drugs in children with attention deficit problems. 

With that I wrap up my first post on this blog.  I hope you found it interesting, and if you have any suggestions for topics involving the interface of science (especially chemistry) and popular culture, write them in the comments.