The Days of the Triffids

Apart from the awful spectacle of COVID-19 wreaking worldwide destruction on the human race, there have been some interesting side effects on the planet in general. People have been going out less, and areas of cities that used to be busy can now look extremely deserted. This has encouraged many of the creatures who are naturally wary of us to come out of hiding and fill the spaces we have vacated. Walking around the campus of the University of Chicago in the early morning, there are notably more rabbits, squirrels and racoons around, even the occasional coyote. More birds as well. People are also traveling less resulting in reduced use of fossil fuels. A decrease in the number of cars, planes and trains has greatly impacted humanity’s carbon footprint and improved the air quality in many places. It is certainly a pleasant experience to be able to rub shoulders with more of our animal neighbors and to breathe cleaner air. But it does give one pause for thought. Now we are not imposing ourselves on Nature so effectively, any number of things might happen. In addition to animals, what about plants?

In 1951, the great science fiction writer John Wyndham published his science fiction classic, “The Day of the Triffids.” In case you have never read it (and you should), here is what happens. There is a worldwide disaster when the majority of people in the world go blind and the remaining members of society, who can still see, are left to try to sort everything out. There is one problem in particular: the triffids. Triffids are tall, malevolent plants that have long stingers which they can use to incapacitate humans or animals—they are carnivorous. They are also ambulatory. If their stingers are docked, then they seem harmless enough and people even keep them in their gardens for ornamental purposes. The stingers take around two years to regenerate and so they need to be docked again periodically. Nobody knows where triffids originally came from but it is thought that they resulted from bioengineering experiments in the USSR.

Original cover of “The Day of the Triffids”

As it turns out, triffids are also the source of a very useful kind of oil, so humans breed them and keep them chained up in large fields surrounded by fences. So far, so good. But perhaps the triffids are also sentient? This isn’t an issue until most people go blind, and the triffids escape from their enclosures and go on a rampage. Soon they have “taken over” and…then…! Of course, plants like triffids don’t really exist; or do they?

Which brings me to the giant hogweed—Heracleum mantegazzianum. The giant hogweed is a really huge plant and can easily grow to between 15 and 20 feet tall. It is umbelliferous, which means that its inflorescence is displayed as numerous umbels consisting of stalks that spread out like an umbrella. Umbels are a characteristic of plants in the Apiaceae family that includes carrot, dill, fennel and Queen Anne’s lace. The stalk of the giant hogweed is a hollow tube (they are often used by unsuspecting children as pea shooters) covered in sharp bristles and purple splotches. Basically, the giant hogweed looks like Queen Anne’s lace on steroids; it’s a very menacing-looking plant.

The giant hogweed and potential victim

And, even though the giant hogweed cannot attack you with a stinger, it is horribly dangerous. The plant contains a sticky sap. If any of this gets on your skin, you had better watch out. You can even become contaminated by the sap standing up to 20 feet away from the plant. The sap contains chemicals called furanocoumarins. Analysis of the giant hogweed has shown that the concentration of furanocoumarins is maximal in the fruit and sap, intermediate in the leaf, and minimal in the stem. Psoralen is the most prevalent furanocoumarin substance isolated from the plant, and seasonal fluctuations in its content have been observed with maximal plant concentrations occurring in June.

Structures of furanocoumarins found in the giant hogweed
DNA crosslinking by furanocoumarins

Furanocoumarins are horribly toxic and mutagenic because they interact with DNA in the cells of the skin. They not only intercalate into the DNA double helix but, in addition, because of their chemical structure, they can react with light to form short-lived, reactive intermediates, which damage DNA through chemical cross-linking of nucleotides. Cells in the skin that have damaged DNA can’t divide and eventually die, promoting a powerful inflammatory reaction. As a result, when exposed to sunlight, substances like furanocoumarins initiate a chemical reaction with the cells of the skin producing a really nasty syndrome called phytophotodermatitis.

Symptoms of phytophotodermatitis

This ultimately leads to a condition that resembles an excruciating sunburn. A burning, blistering rash appears in the 24 hours following initial exposure, and peaks around 48 to 72 hours. Wet skin, sweating, and heat all enhance the phototoxic response. The result of all of this is a truly ghastly skin condition resulting in erupted inflamed skin which may actually peel away leaving a pulpy sensitive mess underneath which is extremely painful , ripe for infection and can potentially be fatal. The condition can last for weeks. At the very least, the victim may be left with disfiguring scars. In recognition of its malevolent nature, the giant hogweed has found a niche in popular culture as a villain playing on our fears of triffid-like creatures. For example, in an episode of the TV detective series “Rosemary and Thyme,” attempts are made to kill the victim Daniel Kellaway by mixing giant hogweed sap into his skin cream and supplying his bedroom with ultraviolet lighting.

All this may seem bad enough, but the giant hogweed is on the move! It is what is known as an invasive species. The giant hogweed’s enormous umbrella-shaped flowers can measure as large as 2.5 feet in diameter, and an average-sized plant can produce some 20,000 seeds, providing an enormous “invasion potential” if the seeds spread in an uncontrolled manner. And that is exactly what has happened. Left to its own devices, the giant hogweed will rapidly colonize the countryside. It especially likes to grow along the moist banks of rivers.

Take the situation in the UK, for example. The plant originated in the Caucuses but was introduced to the UK by seeds supplied to Kew Royal Botanic Gardens in 1817 from the Russian Gorenki Botanic Gardens. It seems that at the time, some people actually thought that this plant was aesthetically pleasing (as with triffids), and it was widely planted in ornamental gardens. But the giant hogweed had other plans. It escaped and ran rampant throughout the country as an extraordinarily aggressive invasive species. Back in the 1970s, when its colonizing activities were first coming to light, it was part of a national scare. There was even a song about it, entitled “The Return Of The Giant Hogweed!”

Turn and run!
Nothing can stop them, 
Around every river and canal their power is growing. 
Stamp them out! 
We must destroy them, 
They infiltrate each city with their thick dark warning odour. 
They are invincible, 
They seem immune to all our herbicidal battering. 
Long ago in the Russian hills, 
A Victorian explorer found the regal Hogweed by a marsh, 
He captured it and brought it home. 
Botanical creature stirs, seeking revenge. 
Royal beast did not forget. 
He came home to London, 
And made a present of the Hogweed to the Royal Gardens at Kew. 
Waste no time! 
They are approaching. ⸻and so on and so on… !

Because of its invasive nature, governments throughout the world have launched campaigns to rid their countries of the giant hogweed. In the UK for example, The Wildlife and Countryside Act of 1981 lists it in section 14, meaning it is an offence to plant or cause giant hogweed to grow in the wild in England and Wales. Similar laws apply in the USA and other countries where there are now efforts to destroy the plants whenever they are found. However, eradication is not easy. The hogweed is ridiculously persistent—if you go in and cut it down, within a few weeks it will just pop up again. As one environmental official put it, “Once it’s here, it’s here to stay. It’s hard to kick it out once it’s already invited itself in.”

The situation is particularly dire in Russia where (like triffids) the plant first originated. Back in the 1950s and 60s, attempts were made to fill the vast unpopulated regions of the USSR with useful growing plants, with a view to providing collective farms with a source of silage, and so the giant hogweed was distributed on purpose. But the scheme fizzled out, leaving large populations of the plants all over the place with no supervision. Naturally the giant hogweed, known as borshevik in Russia, took advantage of the situation and has spread like crazy all over this vast country. As a recent New York Times article points out, “The giant hogweed is what happens when a land loses its stewards. The [hog]weed is expanding its coverage by about 10 percent every year,” which is very fast indeed, and now regularly colonizes the margins of forests and rivers and can readily be observed in the suburbs of cities. “Even the heavily built-up Moscow region had almost 270 square miles contaminated with giant hogweed this summer, according to the regional government. In the Tver region, which lies between Moscow and St. Petersburg and is the size of Austria, the hogweed has permeated a third of towns and villages.” (1) During the winter, the dying plants leave behind huge desiccated skeletons which are now the most visible feature of the winter landscape in many parts of the country. Although Russia has recently arrived at the conclusion that they should be trying to get rid of the giant hogweed, eradication efforts have been mostly ineffective. And, of course, now with the COVID-19 pandemic in full swing, there are even fewer people around to hinder the advance of the monster weed. The country is likely to become inundated with giant hogweeds if something quite drastic isn’t done soon.

If being burned alive by a giant hogweed isn’t bad enough for you, there are worse things because, of course, there are plants which, like triffids, can deliver a genuine sting—the stinging nettle being an obvious example. Now, hard on the heels of stories concerning the invasion of Russia by the giant hogweed comes news about the plant with the most painful sting in the world. Yes, one might do well to avoid the gympie-gympie plant (Dendrocnide moroides), which is most commonly found in North Eastern Australia and is a good example of the family of Australian “stinging trees” of which there are several different types. Comments from individuals who have encountered the gympie-gympie are revealing—(2)

“North Queensland road surveyor A.C. Macmillan was among the first to document the effects of a stinging tree, reporting to his boss in 1866 that his packhorse ‘was stung, got mad, and died within two hours’. Similar tales abound in local folklore of horses jumping in agony off cliffs and forestry workers drinking themselves silly to dull the intractable pain.

“Writing…in 1994, Australian ex-serviceman Cyril Bromley described falling into a stinging tree during military training on the tableland in World War II. Strapped to a hospital bed for three weeks and administered all manner of unsuccessful treatments, he was sent ‘as mad as a cut snake’ by the pain. Cyril also told of an officer shooting himself after using a stinging-tree leaf for ‘toilet purposes’.

“He’s had too many stings to count but Ernie Rider will never forget the day in 1963 that he was slapped in the face, arms and chest by a stinging tree. ‘I remember it feeling like there were giant hands trying to squash my chest,’ he said. ‘For two or three days the pain was almost unbearable; I couldn’t work or sleep, then it was pretty bad pain for another fortnight or so. The stinging persisted for two years and recurred every time I had a cold shower.’ “Now a senior conservation officer with the Queensland Parks and Wildlife Service, Ernie said he’s not experienced anything like the pain during 44 years work in the bush. ‘There’s nothing to rival it; it’s 10 times worse than anything else – scrub ticks, scrub itch and itchy-jack sting included. Stinging trees are a real and present danger.’”

A scientist who has spent a considerable time studying plants like the gympie-gympie described it as “the worst kind of pain you can imagine—like being burnt with hot acid and electrocuted at the same time.” Indeed, the gympie-gympie is also known as the “suicide plant,” which should tell you something about how people feel after being stung by it.

The gympie-gympie can grow to a height of several feet, probably as large as a decent-sized triffid, but unlike the latter they cannot walk around. Nevertheless, their sting, delivered by small hypodermic-like hollow spines that cover the stalks and leaves, has been reported, as quoted above, to be extremely painful. It seems that once the spines have pierced your skin, they are sometimes difficult to remove and can engender a severe allergic reaction which naturally adds to the long-term unpleasantness of the entire experience. Really serious cases have led to the death of animals and occasionally even humans. It is clear that the hypodermic needle-like structures that surround the plant inject a toxin into its victims. One might imagine that the type of toxins used by a plant would be extremely different from those used by animals such as stinging insects, but a recent publication in the journal Science Advances (3) has shown that the actual answer is very surprising. In the new paper, Gilding et al. isolated a novel group of 36 amino acid peptides from the D. moroides and related stinging trees which they named gympietides. These peptides contain multiple cysteine residues which means they can form several disulfide bonds and fold up tightly to form highly stable knot-like shapes called cystine knots or knottins, structures that are resistant to heat or acid denaturation or hydrolysis by proteases. Indeed, this structural motif has been observed in many other biologically active peptides including several animal toxins, some of which are known to produce intense pain including the δ-therapotoxins from tarantulas, δ-hexatoxins from the Sydney funnel web spider, and the δ-conotoxins from cone snails. Interestingly, the mechanism of action of toxins of this type is generally known. Pain or nociception is normally initiated by sensory nerves that innervate the skin or internal organs. These nerves, termed nociceptors, are primed to respond to potentially tissue-damaging stimuli in order to act as warning signals. One important defensive strategy that insects and animals have developed is to produce venoms containing toxins that act by stimulating these nerves as a way of discouraging predators. Nociceptors signal pain by firing action potentials which depend on the opening and closing of voltage-dependent sodium channels (Navs). As it turns out, there are several subtypes of these channels and the complement of channels found in nociceptors is rather unique, containing populations of Nav1.7, 1.8 and 1.9 channels. The consequences of altering the normal behavior of such channels is clear from the effects of mutations that are known to occur in the human population. For example, rare mutations that inactivate the Nav1.7 channel result in complete absence of pain (Congenital Insensitivity to Pain). Not touch or itch—just pain. On the other hand, mutations that cause inappropriate activation of this channel produce extremely painful syndromes, such as erythromelalgia or Paroxysmal Extreme Pain Disorder, which are typified by burning pain in the extremities accompanied by profound neurogenic inflammation.

Ouch! Needle-like structures on the leaves of the gympie-gympie tree

When the authors of the Science Advances article (3) injected small amounts of the purified gympietide into the paws of mice, they noted that this appeared to be painful and so they then investigated the mechanism of action behind this effect. What they observed is that the toxin produced similar effects on pain neurons to the mutations that produce intense pain syndromes in humans. Normally, when sodium channels activate and initiate the firing of an action potential, they then inactivate. But in the presence of gympietide, the Nav1.7 channels observed in sensory neurons remained open, providing a long-lasting depolarizing stimulus to the neuron and repetitive firing of action potentials, delivering a powerful pain signal. The effects of the toxin also seemed to be irreversible; its effects could not be washed away, indicating that the toxin bound to sodium channels very tightly. The effects of gympietides are reminiscent of some insect toxins. The insect with the most painful sting ever recorded is known as the bullet ant, a native of the Amazon. The major toxic component of bullet ant venom, known as poneratoxin, has a similar effect on Nav1.7. No wonder the effects of gympietides are so painful when injected into the paw of a mouse or a human. The discovery of these new peptide toxins is the first time that molecules of this type have been discovered in plants rather than animals, and it represents an interesting example of convergent evolution with respect to the use of venoms, as well as their delivery. The hypodermic devices of the plant clearly have structural analogies in the teeth of serpents, stingers of insects and similar devices.

It is clear that there are many aspects of the biology of the giant hogweed and the gympie-gympie tree that are reminiscent of triffids, although neither of these plants is able to walk around, at least as far as we know. Nevertheless, as human beings become more and more isolated in their homes and our cities and countryside become less contaminated by human intervention, who knows what will come to pass? What is it tapping on your window at night? Is it just the wind? Perhaps it would be a good idea to keep an eye on your garden in these troubled times?

References

1) A Toxic Alien Is Taking Over Russia

By Maria Antonova, Oct. 3, 2020

2) Gympie Gympie: Once stung, never forgotten

By Amanda Burdon, June 16, 2009

3) Neurotoxic peptides from the venom of the giant Australian stinging tree

Gilding EK, Jami S, Deuis JR, Israel MR, Harvey PJ, Poth AG, Rehm FBH, Stow JL, Robinson SD, Yap K, Brown DL, Hamilton BR, Andersson D, Craik DJ, Vetter I, Durek T.
Sci Adv. 2020 Sep 16;6(38):eabb8828. Print 2020 Sep.
doi: 10.1126/sciadv.abb8828. PMID: 32938666