King Joffrey (Copyright by HBO, use for discussion qualifies as fair use under United States copyright law)

So the vile and young King Joffrey Baratheon finally met his demise.  And for most fans of the exceedingly popular HBO series “Game of Thrones” it was a joyous event.  I think he’s just misunderstood . . . the poor lad.

So how did he die?  By poison of course, probably in his wine or food.  But which poison?  That’s the million dollar question, and one that has been tackled quite well by Rachel Nuwer on BoingBoing and fellow chemist Dr. Raychelle Burks on Scientopia.  But I have another idea, otherwise I wouldn’t be writing this.

Each writer took a different route in explaining what poison could have been used.  Rachel Nuwer looked at poisons that most closely resembled the symptoms shown visually during the episode, and came up with cyanide as a likely culprit.  That would have been my first guess, as it has been used for murder and suicide for centuries.  But then I read Dr. Burks piece, and she attempted to marry the poison to the description given in the books by George R.R. Martin, on which the “Game of Thrones” series is based.  She came up with strychnine, which more closely matches the books’ descriptions than cyanide, and could give similar symptoms and cause of death.

Will we ever really know what the poison dubbed “the strangler” is?  Of course not.  Both the books and the series are works of fiction, and both art forms will take liberties and license to put on a good show.  Especially TV and film – it doesn’t matter how realistic it is, as long as it looks good.  But it’s a fun exercise and game to play, so let’s get started.

So here’s what we know from the video evidence:

• King Joffrey drinks wine and a bite of pie
• He complains his throat is dry
• He vomits, is unable to breath, and turns bluish
• Blood forms around his eyes and from his nose, and red spots form on his face

Taken step-by-step King Jeffrey consumed a poison and then has an instant dry throat.  A dry throat – lack of saliva – is a clue that the poison could be one that works against the parasympathetic nervous system (PNS).  The effects of stimulating the PNS can be remembered by the acronym SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI upset, and Emesis.  So any drug that works against the PNS would effectively stop salivation (and keep you from going poo…I just wanted to write the word “poo”).

Then he vomits.  Wait a minute . . . that’s emesis, the E in SLUDGE.  So now we have something activating the PNS, when just a minute ago we had something working against the PNS.  Welcome to TV.  He then can’t breath and turns blue.  This is called asphyxiation and cyanosis, and happens when you can’t breath and deprive the tissue near the skin of oxygen.  Lots of things cause this, from drugs, to accidents, to homicides.

Petechiae

Now, the blood around the eyes and red spots on the face.  This is called petechiae, and is caused by the bursting of blood vessels in the face and eye region.  This is commonly seen at autopsy when someone has been strangled or by some other type of traumatic asphyxiation – like when a car has fallen on someone’s chest.  But it can also happen when someone has extreme bouts of coughing or vomiting.  So the combination of being unable to breath, turning blue, and having petechiae makes a whole lot of sense, and points towards something that would make poor King Joffrey’s heart and chest clench tight, or contract.  The excessive blood pouring from the nose . . . that’s the stuff of Hollywood, or perhaps King Joffrey has another underlying medical condition

Let’s get on with the written evidence:

From George R.R. Martin’s book “A Clash of Kings” we read:

“It was made from a certain plant that grew only on the islands of the Jade Sea, half a world away.  The leaves had to be aged, and soaked in a wash of limes and sugar water and certain rare spices from the Summer Isles. Afterward they could be discarded, but the potion must be thickened with ash and allowed to crystallize. The process was slow and difficult, the necessaries costly and hard to acquire. . . Dissolved in wine, it would make the muscles of a man’s throat clench tighter than any fist, shutting off his windpipe. They said a victim’s face turned as purple as the little crystal seed from which his death was grown, but so too did a man choking on a morsel of food.”

Now we’re getting somewhere.  So it’s made from a plant that is non-native to the “Game of Thrones” realm that’s probably in Europe, and half a world away.  That narrows it down to the Americas or Asia.  The leaves are dried and soaked in limes.  Hmmm, sounds like some sort of acid-base extraction to me, with the acidic limes acting as the acid and making the poison more soluble in water. This makes whatever the poison is basic.  That doesn’t rule out much, as many drugs and poisons are basic, but hey, it’s a clue.  Then it has ash added to it and crystallized.  The ash probably neutralizes the acidic lime solution or forms a counter ion with the poison that enables it to be made solid – as opposed to a liquid.  It is also still soluble in water, and wine, and some sort of salt form of the poison should be water soluble.

The poison works by clenching the throat with the victim’s face turning purple.  That sounds an awful lot like muscular contraction and resulting asphyxia.  The purple face would be cyanosis, as we discussed earlier.

Putting all the pieces together, I come up with . . . nicotine, from tobacco leaves.  And let’s work backwards, from the isolation of the poison to the symptoms and death.

Tobacco leaves by Dannele Bailey (CC BY-ND 2.0)

Tobacco is not native to Europe, and did not make a formal introduction until the early 1500’s.  It is however, native to the Caribbean Islands, and North, Central, and South America.  The large tobacco leaves are typically dried before use and for storage.  There are any number of islands “half a world away” that could produce tobacco leaves.  A chemical, and one of Nature’s Poisons, found in tobacco is nicotine.  Nicotine is a basic alkaloid, and as such is bitter (hence the sugar to mask the taste), and present in dried leaves at a concentration of ~3%.  The acidic limes and juice (pH ~2.5) would protonate the tertiary amine and hasten the extraction of nicotine into the water.

So to recap: we’ve isolated a poison from plant leaves found half a world away.  But what about the physical symptoms of nicotine poisoning and death from it?  Let’s take a look.

Nicotine is an agonist (activator) of the nicotinic acetylcholine receptors, as part of the PNS.  And from what we learned earlier, the SLUDGE mnemonic that you all remember, would trigger emesis (vomiting).  This is a very common symptom of nicotine poisoning, and seen in children and pets when they get hold of their parent’s cigarettes, or more recently e-cigarettes (which I wrote about here).  Whoaaa . . . dry throat isn’t involved with this, you say.  King Joffrey should be salivating, not drying up.  True, but maybe he is just unable to swallow, and using thirst as a reason to drink something to help him.

Nicotine structure

Now for the clenched throat asphyxiation part.  Toxic amounts of nicotine induces smooth muscle contraction (1).  Smooth muscle are those muscles that are involuntary, and include the blood vessels, arteries, aorta, and veins.  Smooth muscle is also found in the trachea (“throat”) and the lungs (2).  Constriction of airway smooth muscle, and the inability or decreased ability to breath, would definitely feel like someone strangling you.  When people are being strangled, or in a case of traumatic asphyxia, they often hold that “one last breath.”  This exerts a force upon your body, especially in the face and eye region, that causes blood vessels to burst, resulting in petechiae.  Go ahead, hold your breath and tighten your lungs and chest as much as you can.  Feel pressure in your face?  That’s vessels ready to burst.  You can stop now.

Without the ability to breath due to airway smooth muscle contraction, and with decreased amounts of blood and oxygen pumping due to vascular contraction, you would die.  You’d likely be cyanotic and tinged a bit blue, and you’d probably have petechiae as you fought to breathe, like in the picture above.  You’d definitely vomit.  Probably a lot.  So nicotine poisoning adds up, almost perfectly.  The last thing to consider is, how toxic is nicotine?  Is a small dose likely to kill?

Nicotine is extremely toxic, make no mistake about it.  Historically, and what is ingrained in every Toxicologist’s head, is that the dose needed to kill an adult is about 50 milligrams (mg).  This is a small amount, and in pure liquid form, one lowly little drop.  Just one.  There is some debate about this, and the lethal dose may indeed be higher, but the argument and evidence isn’t convincing (3).  Lets assume that “the strangler” is an impure solid form (a salt) of nicotine.  For argument’s sake let’s call the salt 75% pure.  A teaspoon of kosher salt weighs about 4 grams (4000 mg), which we’ll approximate for our nicotine poison.  An one-eighth teaspoon dose would be a small amount and easy to dissolve into a goblet of wine.  That much would contain approximately 375 mg  of nicotine, more than seven times the historically used value of 50 mg.  Heck, even a half-teaspoon isn’t much, and could pack a 1500 mg nicotine punch, more than enough to kill.  And if the wine goblet was nearly empty when the poison was added, a single swig could be enough to kill King Joffrey.

So that’s it.  The mystery poison is nicotine.  At least that’s my story and I’m sticking to it.  Poisonous fun with fiction!

References:
1. Hahn, H.l., M. Lang, S. Bleicher, S. Zwerenz, and C. Rausch. “Nicotine-induced Airway Smooth Muscle Contraction: Neural Mechanisms Involving the Airway Epithelium.” The Clinical Investigator 70.3-4 (1992): 252-62.
2. Amrani, Yassine, and Reynold A. Panettieri. “Airway Smooth Muscle: Contraction and beyond.” The International Journal of Biochemistry & Cell Biology35.3 (2003): 272-76.
3. Mayer, B. “How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century.” Arch Toxicology 88.1 (2014): 5-7.