Monday, 10 October 2016

The James Bond of Plant Poisons

Bond, Poisoned by a Plant - Remember when Le Chiffre poisoned James Bond in Casino Royale? The poison makes James’ heart beat erratically and he stumbles to his car. Then the brains back at MI6 identify the toxin as “Digitalis”, and an antitoxin and defibrillator save Bond in time for him to win another round of poker. The poison has only a few minutes on screen, but the scene is exciting! Big surprise: we have a plant to thank for this excitement – and much more!

Figure 1: Digitalis (Foxglove) flowers. While foxglove plants synthesize some chemicals that turn their flowers beautiful colors to attract insects, they also synthesize chemicals that can be used as deadly poisons. How have humans used these toxins?
Foxgloves make digoxin, a deadly poison - As nature’s master chemists, plants synthesize a huge variety of chemicals that carry out specific parts of the plant’s will. Species in the Digitalis genus (Foxgloves) fill their flowers with chemicals that impart beautiful white, yellow, blue, and purple flowers and attract insect pollinators (Figure 1). However, at the same time, these plants synthesize other chemicals that pack a deadly punch. All parts of the plant contain digoxin, a chemical compound that if eaten in large quantities disables heart rate regulation and can lead to weakness or collapse, seizures, and even death.

Plants combine benign chemicals to make glycoside toxins - Foxglove plants make digoxin by binding together benign compounds: sugars and steroids. Binding sugars to steroids is a common strategy many plants use to make poisonous chemicals. These two-part chemicals are called glycosides. For example, plants in the Scilloideae and Apocynaceae families also bind sugars to steroids to make the glycoside poisons Scilliroside and Ouabain (Figure 2).

Figure 2: Examples of poisonous glycosides made in some plant families. These poisonous glycosides are all made by binding together sugar (in blue) and a steroid (in purple). The plant family in which each glycoside is found is shown to the right of the chemical structure. For example, the top glycoside called digoxin is found in the Digitalis family, shown in the top photo.

Historical uses of glycoside poisons - Humans noticed and started taking advantage of the effects, or bioactivities, of glycosides hundreds of years ago. The Eastern Africans used chemical Ouabain to poison arrowheads for hunting and warfare as early as the 3rd century BC [1], and the chemical Scilliroside is used as a rodenticide [2]. The interesting cardiac effects of the digoxin prompted its investigation as early as 1785 [3], with one main question: if administered in minute quantities, could digoxin be used to help individuals with heart problems?

Though toxic, glycosides are medicinal in small doses! - After much study scientists and doctors have found that digoxin can be used to treat atrial fibrillation, atrial flutter, and sometimes heart failure – and digoxin has been added to the World Health Organization’s List of Essential Medicines. For this chemical to help with heart conditions, it needs to be present in the blood at a concentration between 0.8 – 2.0 nanograms per milliliter (ng/ml) of blood [4]. Unfortunately, if digoxin levels increase above 2.0 ng/ml, the compound quickly becomes toxic and can revert from medicine to poison. So, to prevent poisonous digoxin levels maybe Bond should think about taking smaller sips of drinks offered to him by enemies.

[1] Neuwinger, Hans Dieter. African Ethanobotany: Poisons And Drugs. Weinheim: Chapman & Hall, 1996.
[2] el Bahri, L.; Djegham, M.; Makhlouf, M. (2000). "Urginea maritima L. (Squill): A Poisonous Plant of North Africa". Veterinary and Human Toxicology. 42 (2): 108–110.
[3] Withering, William (1785). An Account of the Foxglove and some of its Medical Uses With Practical Remarks on Dropsy and Other Diseases.
[4] Richard C. Dart. Medical Toxicology. Lippincott Williams & Wilkins, 2004