This past weekend, my favorite baseball team -- the Oakland Athletics -- did the impossible. They swept the mighty, mighty New York Yankees in a four game series. They hadn't done that in 40 years. It was pure awesomeness.
What does that have to do with chemistry? I'll tell you.
First, the main reason that I like the A's so much is chemistry related. I started my Ph.D. at Berkeley in the late 90s which turned out to be a period of great success for the team. It was the beginning of the Moneyball era when the A's managed to make the playoffs 5 times from 2000 to 2006 despite having a much lower payroll than a lot of the competition. When I attended my first game at the Oakland Coliseum in 1998, a limited number of tickets were available for Wednesday day games at $1 apiece. Since the A's kinda sucked in '98, and the Coliseum was (and is) considered to be one of the worst parks in baseball, fans weren't exactly lining up overnight for those cheapo seats. On top of the $1 tickets, you could also get $1 hot dogs. A miserable chemistry grad student would be a fool not to cash in on such a generous offer. And so I did. And I fell for the team.
Second, a couple years ago friend of mine quizzed me with the following question: Who are the five A's players that share a surname with a famous chemist? If you're not a chemist or an A's fan, you couldn't possibly care less about this. I am both, so I care a lot. I'll give you the answer so you don't hurt your brains trying to remember the 2010 A's roster.
1.) C Kurt Suzuki. Same last name as Nobel Prize Winner Akira Suzuki.
2.) 1B Daric Barton. Same last name (and homonym first name) of Nobel Prize Winner Sir Derek Barton.
3.) RP Michael Wuertz. Same last name as 19th century chemist Charles-Adolphe Wuertz.
4.) RP Brad Ziegler. Same last name as Nobel Prize Winner Karl Ziegler.
5.) RP Craig Breslow. Same last name as influential Columbia faculty member and recent originator of the antipodal space dinosaur theory, Ron Breslow.
Three Nobel Laureates on one roster? Pretty nice, eh? Well, good enough for a 0.500 season, anyway. Maybe they just needed a Woodward or Corey or Grubbs to push them into the playoffs.
Okay, that was neat for me. I'll come up with something a little less obscure for my next post.
Monday, July 23, 2012
Thursday, July 19, 2012
Lucius Fox -- Super Med Chemist Extraordinaire
The process of drug discovery is long and arduous. It's filled with also sorts of difficult challenges for chemists. Balancing potency against selectivity. Optimizing physical properties in order to produce compounds with reasonable pharmacokinetic profiles. Minimizing toxicity and drug-drug interactions. It's difficult to be both fast and successful....unless you work for Batman.
In Batman Begins (The first Christian Bale Batman movie, in case you forgot), our hero gets himself blasted with an aerosolized psychotropic agent of some sort when he confronts Dr. Jonathan Crane, aka The Scarecrow. Things go all Helter Skelter for Batman. It's not a happy trip like you might experience in a Beatles movie or an episode of Mad Men. After being set on fire and falling out a window, Batman puts himself out and escapes to a rooftop where his elderly butler, Alfred, can easily rescue him. Seems plausible.
In the next scene, Batman has been stripped of his bat-cape and bat-cowl and bullet-proof bat-suit, and he's lying in his bed in his decidedly unbatty PJs. He's Bruce Wayne again, and he's lucid. No more nasty drug-spawned visions for him. Alfred is there, but so is Lucius Fox -- head of Wayne Enterprises' Cool Products That Could Be Helpful If You Become A Nocturnal Super Vigilante Division. Bruce is a little surprised to see Lucius, because Lucius hasn't officially been let in on the whole Batman alter-ego thing. He gets over it quickly, though because Lucius is wise, helpful, and humble. Of course he is. He's portrayed by Morgan Freeman. We all learn together that Lucius is responsible for Bruce's recovery:
LUCIUS FOX: I analyzed your blood, isolating the receptor compounds and the protein based catalyst.
BRUCE WAYNE: Am I meant to understand any of that?
LUCIUS FOX: Not at all. I just wanted you to know how hard it was. Bottom line, I synthesized an antidote.
BRUCE WAYNE: Could you make more?
LUCIUS FOX: Are you planning on gassing yourself again, Mr. Wayne?
BRUCE WAYNE: Well you know how it is Mr. Fox. You're out at night looking for kicks. Someone is passing around a weaponized hallucinogen...
LUCIUS FOX: I'll bring what I have. The antidote should inoculate you for now.
In addition to being in charge of bullet-proof bat-suit construction and super awesome jet car development and maintenance, Lucius is pretty handy at drug development. In the course of just a couple days at most, he draws and processes Bruce's blood, identifies "the receptor compounds" and the "protein-based catalyst" (we call that guy an 'enzyme' in the Biz), hypothesizes an agent that will antagonize these materials, synthesizes it, establishes its efficacy in some model or other, and then injects it into Mr. Wayne, thus curing him. Ta Da!
I could spend this paragraph scrutinizing Lucius's remarkable achievement. I could point out that his ridiculous timeline benefited from the fact that he didn't have to jump through a lot of the time-killing hoops of drug discovery. He didn't have to run any clinical trials or satisfy any regulatory requirements, and for that matter, since his antidote was delivered by syringe, it didn't have to be designed to penetrate the gut. I could point that stuff out (maybe I just did), but I'd rather focus on what this accomplishment means and what Lucius Fox represents. He's the classic pop culture science guy.
The history of American popular culture is littered with folks like Lucius Fox. From James Bond's buddy Q to Iron Man Tony Stark to Gil Grissom to Abby Sciuto to Walter White, we have been provided with an archetypal super scientist/engineer who has a strong enough grasp of all fields of scientific inquiry to solve pretty much any problem that springs up that requires more brains than brawn. Create a super-intelligent nerd character and you can big brain your way out of any jam you might encounter.
Unfortunately, science doesn't generally work this way. An individual scientist might have a broad enough background to understand multiple fields, but he or she usually specializes in one. The process of drug discovery at which Lucius acquitted himself so admirably, requires buckets of skilled people with all sorts of different training. You need enzymologists, pharmacologists, cellular biologists, structural biologists, medicinal chemists and more. Within medicinal chemistry, certain research organizations (I can think of one that starts with a silent P followed by a big ol' noisy F) have decided that the process of thinking of molecules to make should be performed by people other than the folks that actually synthesize them. Except in the world of action heroes, spies, and uber-competent criminal investigation teams, Lucius Fox is a rare bird. Batman should be very grateful to have him. Any drug company would be.
In Batman Begins (The first Christian Bale Batman movie, in case you forgot), our hero gets himself blasted with an aerosolized psychotropic agent of some sort when he confronts Dr. Jonathan Crane, aka The Scarecrow. Things go all Helter Skelter for Batman. It's not a happy trip like you might experience in a Beatles movie or an episode of Mad Men. After being set on fire and falling out a window, Batman puts himself out and escapes to a rooftop where his elderly butler, Alfred, can easily rescue him. Seems plausible.
In the next scene, Batman has been stripped of his bat-cape and bat-cowl and bullet-proof bat-suit, and he's lying in his bed in his decidedly unbatty PJs. He's Bruce Wayne again, and he's lucid. No more nasty drug-spawned visions for him. Alfred is there, but so is Lucius Fox -- head of Wayne Enterprises' Cool Products That Could Be Helpful If You Become A Nocturnal Super Vigilante Division. Bruce is a little surprised to see Lucius, because Lucius hasn't officially been let in on the whole Batman alter-ego thing. He gets over it quickly, though because Lucius is wise, helpful, and humble. Of course he is. He's portrayed by Morgan Freeman. We all learn together that Lucius is responsible for Bruce's recovery:
LUCIUS FOX: I analyzed your blood, isolating the receptor compounds and the protein based catalyst.
BRUCE WAYNE: Am I meant to understand any of that?
LUCIUS FOX: Not at all. I just wanted you to know how hard it was. Bottom line, I synthesized an antidote.
BRUCE WAYNE: Could you make more?
LUCIUS FOX: Are you planning on gassing yourself again, Mr. Wayne?
BRUCE WAYNE: Well you know how it is Mr. Fox. You're out at night looking for kicks. Someone is passing around a weaponized hallucinogen...
LUCIUS FOX: I'll bring what I have. The antidote should inoculate you for now.
In addition to being in charge of bullet-proof bat-suit construction and super awesome jet car development and maintenance, Lucius is pretty handy at drug development. In the course of just a couple days at most, he draws and processes Bruce's blood, identifies "the receptor compounds" and the "protein-based catalyst" (we call that guy an 'enzyme' in the Biz), hypothesizes an agent that will antagonize these materials, synthesizes it, establishes its efficacy in some model or other, and then injects it into Mr. Wayne, thus curing him. Ta Da!
I could spend this paragraph scrutinizing Lucius's remarkable achievement. I could point out that his ridiculous timeline benefited from the fact that he didn't have to jump through a lot of the time-killing hoops of drug discovery. He didn't have to run any clinical trials or satisfy any regulatory requirements, and for that matter, since his antidote was delivered by syringe, it didn't have to be designed to penetrate the gut. I could point that stuff out (maybe I just did), but I'd rather focus on what this accomplishment means and what Lucius Fox represents. He's the classic pop culture science guy.
The history of American popular culture is littered with folks like Lucius Fox. From James Bond's buddy Q to Iron Man Tony Stark to Gil Grissom to Abby Sciuto to Walter White, we have been provided with an archetypal super scientist/engineer who has a strong enough grasp of all fields of scientific inquiry to solve pretty much any problem that springs up that requires more brains than brawn. Create a super-intelligent nerd character and you can big brain your way out of any jam you might encounter.
Unfortunately, science doesn't generally work this way. An individual scientist might have a broad enough background to understand multiple fields, but he or she usually specializes in one. The process of drug discovery at which Lucius acquitted himself so admirably, requires buckets of skilled people with all sorts of different training. You need enzymologists, pharmacologists, cellular biologists, structural biologists, medicinal chemists and more. Within medicinal chemistry, certain research organizations (I can think of one that starts with a silent P followed by a big ol' noisy F) have decided that the process of thinking of molecules to make should be performed by people other than the folks that actually synthesize them. Except in the world of action heroes, spies, and uber-competent criminal investigation teams, Lucius Fox is a rare bird. Batman should be very grateful to have him. Any drug company would be.
Sunday, July 15, 2012
Pilot episode of X-Files
On September 10, 1993, Fox first broadcast the pilot episode of The X-Files (titled: Pilot), and the next chapter in the world of cult network television began. Like Twin Peaks before it and Lost much later, The X-Files was defined by wonderful creepiness, mystery, and not a small amount of outright confusion. I loved it.
I'm not going to get into the plot summary of the episode. You can read about it on your own, or watch it on Netflix-streaming if you like. I'm going to focus largely on one scene. The scene which presumably inspired organic chemists to hop off their couches on that day in 1993 and cry, "Did you see that?" to their indifferent loved ones. Yes, the pilot episode of The X-Files included a brief glimpse of an honest-to-goodness organic molecular structure.
The scene in question is ridiculously expository. In fact, a lot of the early scenes are. That just comes with being a pilot episode. You have to introduce the show's concept somehow, and the easy way is to have the characters spell things out in plain language even if that type of thing rarely happens in real life. For example, in an earlier scene (the only earlier scene), at their prompting, Agent Dana Scully spouts off the professional history of Agent Fox Mulder to a room full of mysterious, suited, middle-aged white men who are clearly in charge of something (possibly everything). She does this despite the fact she's never met Agent Mulder, and the men to whom she's speaking know everything about him. Obviously, this is all for the benefit of the audience. We learn that Dana Scully is a smartypants who keeps up on FBI lore, and we learn that Fox Mulder is an "Oxford-educated psychologist" who needs to be spied on. Boom! One scene densely-packed with back story and we're on our way.
In the scene with the chemical structure, it's Fox Mulder's turn to teach us about Dana Scully. She wanders down to his basement office to introduce herself to her new "partner" (Mulder's office arrangements remind me a little of Milton's situation from Office Space. I wonder if the FBI had secretly quit paying him, too). Mulder takes the opportunity to recite Scully's educational and professional history to her. Now we know he, too, is a smartypants who keeps track of people within the Bureau, and that she has a physics undergraduate degree complete with an impressive-sounding senior thesis which she followed up with a medical degree that led her to the FBI where she teaches at the Academy. Whew! I'm glad we got all that straight. Exposition over. Time to get into an investigation. And without taking a breath, they do.
Mulder has been following a series of murders of some kids from the class of 1989 of the same high school in Oregon. Mulder conveniently has a slide presentation of the evidence uncovered thus far (these days he'd use PowerPoint, of course). The autopsy results haven't provided any compelling cause of death, but each of the victims has a pair of relatively nondescript red spots on his or her back. After presenting this much to Scully, the following exchange ensues:
MULDER: How's your chemistry? (advancing to the next slide) This is the substance found in the surrounding tissue.
SCULLY: It's organic. I don't know. Is it some sort of synthetic protein?
MULDER: Beats me. I've never seen it before, either.
Here's what's on the slide:
Again, I drew this myself. It's pretty close to what showed up on the screen in Mulder's office.
I have to say I think Scully addressed Mulder's inquiry pretty well. As a doctor she should definitely be able to recognize whether or not a chemical structure is organic. Even so, she acknowledged that she didn't really know what the structure was, and then she made a reasonable guess that suggested she could recognize a peptide. That's the type of thinking you're expected to show in your qualifying exams in graduate school. She gets a B- in my book.
Here's how the conversation might have gone had a trained organic chemist been involved:
MULDER: How's your chemistry? (advancing to the next slide) This is the substance found in the surrounding tissue.
CHEMIST: It looks like it's supposed to be a tripeptide of some sort. I couldn't say much about it without knowing what the R groups are. By the way, you know that the lone pairs don't have to be explicitly drawn on the carbonyl oxygens, right?
MULDER: Huh. Well...I'm a little out of practice with my structures I guess. I should have spent more time on that at Oxford.
And what role does this generic peptidey compound play in the rest of the episode? Absolutely none, and that's sad, I think. The whole exercise of including the chemical structure is just another piece of exposition. It's a throw away moment meant to demonstrate that the psychologist and the physics-trained medical doctor knew their way around the chem lab, too. In fact, they're so chemically knowledgeable that merely failing to recognize a random tripeptide (ill-defined as it was) makes the molecule suspicious. Ultimately, chemistry is taken for granted, as it often is. It's just a tool for the writers to establish that Mulder and Scully are scientifically well-rounded and wicked smart.
I'm not going to give The X-Files characters too much guff, though. Not Scully, anyway. In the middle of the episode she has the following line during an argument with Mulder about his desire to employ fantastical theories to explain the evidence they have:
"What I find fantastic is any notion that there are answers beyond the realm of science. The answers are there. You just have to know where to look."
That's a real scientist. I knew there was a reason I had a crush on her. And she clings to this philosophy even as the most inexplicable ridiculous crap happens around her...at least until she gives birth to the alien baby.
I'm not going to get into the plot summary of the episode. You can read about it on your own, or watch it on Netflix-streaming if you like. I'm going to focus largely on one scene. The scene which presumably inspired organic chemists to hop off their couches on that day in 1993 and cry, "Did you see that?" to their indifferent loved ones. Yes, the pilot episode of The X-Files included a brief glimpse of an honest-to-goodness organic molecular structure.
The scene in question is ridiculously expository. In fact, a lot of the early scenes are. That just comes with being a pilot episode. You have to introduce the show's concept somehow, and the easy way is to have the characters spell things out in plain language even if that type of thing rarely happens in real life. For example, in an earlier scene (the only earlier scene), at their prompting, Agent Dana Scully spouts off the professional history of Agent Fox Mulder to a room full of mysterious, suited, middle-aged white men who are clearly in charge of something (possibly everything). She does this despite the fact she's never met Agent Mulder, and the men to whom she's speaking know everything about him. Obviously, this is all for the benefit of the audience. We learn that Dana Scully is a smartypants who keeps up on FBI lore, and we learn that Fox Mulder is an "Oxford-educated psychologist" who needs to be spied on. Boom! One scene densely-packed with back story and we're on our way.
In the scene with the chemical structure, it's Fox Mulder's turn to teach us about Dana Scully. She wanders down to his basement office to introduce herself to her new "partner" (Mulder's office arrangements remind me a little of Milton's situation from Office Space. I wonder if the FBI had secretly quit paying him, too). Mulder takes the opportunity to recite Scully's educational and professional history to her. Now we know he, too, is a smartypants who keeps track of people within the Bureau, and that she has a physics undergraduate degree complete with an impressive-sounding senior thesis which she followed up with a medical degree that led her to the FBI where she teaches at the Academy. Whew! I'm glad we got all that straight. Exposition over. Time to get into an investigation. And without taking a breath, they do.
Mulder has been following a series of murders of some kids from the class of 1989 of the same high school in Oregon. Mulder conveniently has a slide presentation of the evidence uncovered thus far (these days he'd use PowerPoint, of course). The autopsy results haven't provided any compelling cause of death, but each of the victims has a pair of relatively nondescript red spots on his or her back. After presenting this much to Scully, the following exchange ensues:
MULDER: How's your chemistry? (advancing to the next slide) This is the substance found in the surrounding tissue.
SCULLY: It's organic. I don't know. Is it some sort of synthetic protein?
MULDER: Beats me. I've never seen it before, either.
Here's what's on the slide:
I have to say I think Scully addressed Mulder's inquiry pretty well. As a doctor she should definitely be able to recognize whether or not a chemical structure is organic. Even so, she acknowledged that she didn't really know what the structure was, and then she made a reasonable guess that suggested she could recognize a peptide. That's the type of thinking you're expected to show in your qualifying exams in graduate school. She gets a B- in my book.
Here's how the conversation might have gone had a trained organic chemist been involved:
MULDER: How's your chemistry? (advancing to the next slide) This is the substance found in the surrounding tissue.
CHEMIST: It looks like it's supposed to be a tripeptide of some sort. I couldn't say much about it without knowing what the R groups are. By the way, you know that the lone pairs don't have to be explicitly drawn on the carbonyl oxygens, right?
MULDER: Huh. Well...I'm a little out of practice with my structures I guess. I should have spent more time on that at Oxford.
And what role does this generic peptidey compound play in the rest of the episode? Absolutely none, and that's sad, I think. The whole exercise of including the chemical structure is just another piece of exposition. It's a throw away moment meant to demonstrate that the psychologist and the physics-trained medical doctor knew their way around the chem lab, too. In fact, they're so chemically knowledgeable that merely failing to recognize a random tripeptide (ill-defined as it was) makes the molecule suspicious. Ultimately, chemistry is taken for granted, as it often is. It's just a tool for the writers to establish that Mulder and Scully are scientifically well-rounded and wicked smart.
I'm not going to give The X-Files characters too much guff, though. Not Scully, anyway. In the middle of the episode she has the following line during an argument with Mulder about his desire to employ fantastical theories to explain the evidence they have:
"What I find fantastic is any notion that there are answers beyond the realm of science. The answers are there. You just have to know where to look."
That's a real scientist. I knew there was a reason I had a crush on her. And she clings to this philosophy even as the most inexplicable ridiculous crap happens around her...at least until she gives birth to the alien baby.
Sunday, July 8, 2012
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.
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:
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.
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