By Vidya Rajan, Columnist, The Times
Plants can be just as deadly to animals as animals are to animals, and this is not hyperbole. In order not to be eaten, plants abound with an alphabet soup of chemicals designed to make the predator so uncomfortable as to leave them alone, or to really make a point by killing them stone cold dead. Here, I want to spend a little time looking at plant toxins and review a few common classes of toxins. I will also briefly review how some of them have been leveraged for use as medicinal and recreational drugs. And I will reveal to you what is considered the nastiest plant in all the world – a tough call in a world brimming with nasties; a plant to which you will want to give a wide berth.
The most interesting plant toxins forthrightly kill animals, with the corollary that the more ghastly or instantaneous the death the more the notoriety. Among the most notorious are the alkaloids curare and strychnine. Curare is the infamous “arrow poison” used to tip arrows for hunting in Central and South America. It is a venom which affects the nervous system by causing respiratory arrest by causing muscles to lose their tone, but it is not a poison and can be safely eaten. Strychnine is found in plants of the Strychnos genus from South Asia, is and used in the region to kill animal pests. Strychnine is a neurotoxin, and it is dangerous both by ingestion and injection. It causes convulsions and respiratory arrest due to ophisthotonus, where muscles contract as in tetanus. Ricin from castor beans is high on the list of infamy as well. It is one of the deadliest toxins known: a grain of ricin the size of a grain of salt could kill a person by inhibiting the function of the ribosome, the essential protein-factory of the cell. Ricin was used in the “umbrella murder” where a gun hidden in the tip of an umbrella was used to shoot a tiny pellet containing ricin at the Bulgarian defector Georgi Markov as he was waiting at a bus stop in London, UK. Although Markov thought he may have been poisoned and mentioned the event to a colleague, the pellet was so small it was not noticed when he ended up in hospital.
The familiar garden plants oleander and foxglove produce the poisons oleandrin and digoxin which are deadly if consumed. Oleandrin was recently proposed by a businessman as a treatment for Covid-19. This suggestion was quickly dispelled by the FDA and scientists who warned that oleander is a toxin with potentially serious health repercussions, and not something to self-medicate with (https://www.webmd.com/lung/news/20200819/experts-reject-oleander-extract-as-covid-treatment#1). Then there is the lacy but deadly shrub poison hemlock, not to be confused with the coniferous hemlock tree. It is common in shady gardens and its leaves are often mistaken for parsley or the feathery tops of carrots. And this would be a deadly mistake. Poison hemlock’s leaves, roots, and flowers are all toxic from the presence of a chemical called coniine. Poison hemlock was the plant used to kill Socrates [1]. He was accused of corrupting the minds of the youth of Athens with free thinking and godlessness, and was asked to select between being exiled from Athens or killing himself. Being Socrates, and the city in question being Athens, he chose death over exile. Coniine’s actions cause flaccid paralysis, similar to curare. Poison hemlock is quite common in the Mid-Atlantic, and I spend a fair amount of time each Spring and Fall pulling out these plants, which seem to thrive in the damp shade of my yard.
On another level are chemicals that make for unpalatability to the casual browser, but that are not toxic at lower doses to humans. These chemicals may taste bad, smell strange, or cause visceral reactions like vomiting, nausea, or hallucinations. Smoked or consumed, these can cause euphoria and altered states of mind. Plants expressing chemicals such as caffeine in coffee beans, nicotine in tobacco, areca nut alkaloids, opium in poppies… the list goes on. These plants and chemicals have been exploited for their mood-altering effects. Their initial purpose was probably to make animals that ate them feel woozy and deter further predation. Alas for these plants some animals, specifically humans, like feeling woozy, and seek out the experience of having their moods messed with. These plants are now cultivated for consumption and constitute a large portion of legal and illegal global trade.
In terms of their chemical makeup, most plant toxins fall into a few classes of compounds. They are usually, although not always, secondary metabolites. Secondary metabolites are not essential for plant survival, but perform other functions, such as protection from predators, attracting pollinators, sunscreen, and resistance against parasites. Due to their shared structural similarities, these molecules interfere with animal biochemistry in similar ways. Knowing their action allows these molecules to be leveraged for use as therapeutics or in research. I have reviewed the most prominent classes of chemicals below.
Glycosides are chemicals which contain a sugar linked to a functional group which mediates the physiological action. Cardiac glycosides such as oleandrin, cardenolide, and digoxin are found in oleander, milkweed, and foxgloves. These chemicals cause the heart to beat more forcefully, but slower, and are used to treat ailments such as congestive heart failure and arrhythmia. They also have neurological effects, and their use as drugs has to be carefully monitored. Cyanogenic glycosides are linked to a cyanohydrin group and release highly toxic hydrogen cyanide upon decomposition [2]. Varying amounts of amygdalin is found in apple seeds, in raw lima beans, and in bitter almonds. Linmarin and lotaustralin are cyanogenic glycosides from cassava, a staple across the tropics. The common method of processing cassava by pounding can release toxic cyanide into the air and into effluent water, intoxicating the handlers and causing a paralytic syndrome that is widespread in areas of Africa where cassava is a staple food. Amygdalin is sold as Laetrile or vitamin B17 as an anticancer drug, but has not been approved by the FDA due to its toxicity (https://www.cancer.gov/about-cancer/treatment/cam/patient/laetrile-pdq).
Alkaloids are a large and varied group containing a heterocyclic ring with a nitrogen, and includes a variety of familiar chemicals used for medicinal and recreational purposes such as caffeine and nicotine. The indole alkaloid, curare, binds to receptors in the neuromuscular junction and causes flaccid paralysis if injected into the body. Because of its large size, it is not absorbed through the digestive lining and so is not poisonous if ingested. It is used as an antidote to strychnine poisoning or against tetanus. Glycoalkaloids such as solanine and chaconine from potatoes can be acutely toxic, and cause gastrointestinal distress and neurological symptoms such as dizziness and confusion at lower levels. Solanine poisoning can be avoided by peeling potatoes and discarding any eye sprouts or greened areas of the tuber. Tomatine is present in the green parts of tomatoes, but apparently is less toxic than solanine. Tropane alkaloids such as atropine, scopolamine and hyoscyamine from deadly nightshade, mandrake, and jimsonweed interfere with the action of the neurotransmitter acetylcholine in both the brain and muscle. Their medical use is for treatment of congestive heart failure and arrhythmias, and as an antispasmodic. Overdosing on these alkaloids are described by a mnemonic: “hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter”[3]. Aconitine from wolfsbane and sanguinarine and dhihydrosanguinarine from Mexican poppy oils (kaktar oil) are norditerpenoids similar in action to tropane alkaloids on the cardiac and nervous system. Aconitine is used in herbal medicines as antipyretics and analgesics, although its fame as a poison in real-life and fictional stories should be a warning against its consumption.
Saponins are a large collection of surfactants are present in over 100 plant families including horse chestnuts, corn cockle, and jack-in-the-pulpit can cause gastrointestinal distress because they interfere with cell membrane structure. They are being investigated for anticancer effects by interfering with angiogenesis and metastasis. Mitotic spindle inhibitors such as taxol from Pacific yew, and vincristine and vinblastine from the Madagascar periwinkle are used in cancer treatments. The May apple, a familiar Spring ephemeral in the Northeast, produces podophyllotoxin in its leaves and rhizomes, which is toxic by stopping DNA replication and cell division. It has been formulated into topical antiviral, antihelminthic, and antitumor drugs.
There are many other classes and types of toxins – pyrethrin from chrysanthemum that inhibits energy production, nephrotoxic oxalates from rhubarb and anthurium, irritating urushiol from poison ivy, hemagglutinating lectins from lentils and beans, psychoactive myristin from nutmeg, and DNA-binding agents such as psoralen from figs and celery – too many to list in detail, but exemplifying the statement that plants are both the world’s pharmacy and its poison cabinet.
As to the promised reveal at the end, the nastiest plant in the world is the giant stinging tree, Dendrocnide excelsa, from Australia [4]. Covered in a sort of fuzz, it looks innocuous, but the fuzz is made of silica needles which inject a venom similar to spider venom. The pain that brings is intense, but also last months and is resistant to morphine. Examination of venom components that are responsible for the horror this tree inflicts revealed a new class of peptides, names gympietides, which not only inflicts the pain but prevents the body from suppressing the pain signals. Australian scientists are now searching for an antidote but, in the meantime, be careful to give the giant stinging tree a wide berth should you happen to go to Australia.
References
- Hotti, H. and H. Rischer, The killer of Socrates: Coniine and related alkaloids in the plant kingdom. Molecules, 2017. 22(11): p. 1962.
- Bolarinwa, I.F., et al., A review of cyanogenic glycosides in edible plants. Toxicology-New Aspects to This Scientific Conundrum, 2016.
- Holzman, R.S., The legacy of Atropos, the fate who cut the thread of life. Anesthesiology: The Journal of the American Society of Anesthesiologists, 1998. 89(1): p. 241-249.
- Gilding, E.K., et al., Neurotoxic peptides from the venom of the giant Australian stinging tree. Science advances, 2020. 6(38): p. eabb8828.
