Daniella Lorman and Clem Doucette

Illustrations by: Alex Tansey, Mara Russell, and Hannah Weisman

A Hot Meal

Life on our planet is facing a serious environmental threat. If we allow greenhouse gas emissions to continue increasing, it is estimated that the Earth’s average surface temperature will rise by roughly 11.5 degrees Fahrenheit by the end of this century [1]. At a glance, 11.5 degrees may not seem like a big change. However, daily air temperatures, or the numbers we see when we check the weather apps on our phone, are vastly different measurements than the average temperature of our Earth’s surface. Seemingly small global temperature increases of two to five degrees Fahrenheit may cause superstorms like Hurricane Sandy and Katrina to occur more frequently [1]. Even greater increases will cause flooding in coastal cities due to rising sea levels. On top of these highly visible impacts, increasing temperatures are causing more obscure — but still immensely dangerous — problems.

Imagine subsisting on a diet consisting solely of white rice and Coca-Cola. After a few days, you would likely begin to feel weak and ill without the nutrients necessary for maintaining your body. The wellbeing of all mammals, including humans, is dependent on their ability to acquire sufficient amounts of food and nutrients. For herbivorous mammals, these intrinsic properties of food are especially important, since many consume plants that contain plant secondary compounds (PSCs) [2]. PSCs are toxic compounds that plants produce in order to deter pests and consumers, such as insects and herbivorous mammals. Under no heat or cold stress (or no temperature extremes), herbivorous mammals can, to an extent, metabolize and detoxify plant compounds. However, with rising global temperatures, plant secondary compounds may become much more toxic and difficult for herbivores to metabolize. In the years to come, this phenomenon, known as temperature-dependent toxicity, may devastate herbivorous mammals across the globe.

Dancing With Death: The Detrimental Effects of Ergot Alkaloid Poisoning

In 1518, a strange plague struck the city of Strasbourg, France. It all started when townspeople observed a woman convulsively dancing through the streets. Soon after, somewhere between 50 and 400 more citizens joined the woman in her frenzied dance, and after continuing for several days, many of those infected died [3]. While contemporary physicians and clergy attributed the plague to demonic possession or witchcraft, today, many suspect that the “dancing fever” was in fact caused by an extreme case of mass ergot fungi poisoning [3]. Ergot are a group of fungi that commonly infect grasses and cereals such as rye, barley, and many varieties of wheat [4]. The relationship between the fungi and the grass is mutualistic, meaning that both species benefit from the fungal infection; the fungus obtains nutrients from the plant, while certain chemicals produced by the fungus shield the plant from predators. These chemicals, created by ergot and other fungi such as Epichloë, are known as ergot alkaloids [4].

While ergot substances proved fatal for the people of medieval Strasbourg, they are often used today for therapeutic purposes and vary considerably in toxicity. Ergot alkaloids are often found in drugs used to treat Parkinson’s disease, migraines, and hemorrhaging [5]. In fact, ergot alkaloids are even found in LSD, a common psychedelic [5]. Although the ecological roles of ergot alkaloids are still poorly understood, evidence suggests they protect fungi and host plants from insects and other predators [5]. In essence, the ergot acts like a guard dog for the grass; in exchange for the protection offered by the dog’s fearsome jaws (i.e. the ergot alkaloids), the owner provides the dog with food and shelter. What, then, gives some ergot alkaloids their bite?

Agroclavin: An Insidious Toxin

Many ergot alkaloids are powerful toxins that can damage mammalian nervous and cardiovascular systems. Agroclavin, a common ergot alkaloid that is both cytotoxic and neurotropic, is one such toxin [5]. Cytotoxic compounds kill cells, and neurotropic ones infect and damage specifically nerve cells, resulting in lasting damage to the nervous system. Agroclavin works by latching onto and activating dopamine receptors, while simultaneously blocking serotonin receptors [6]. This results in an excess of dopamine. Studies conducted on mice and livestock have shown that excess dopamine can impact a wide range of bodily functions, ranging from memory creation to reproduction [6, 7]. Excess dopamine suppresses the reproductive hormone, prolactin, which plays a critical role in the final stages of pregnancy and birth. In horses, prolactin is essential in letting a mare’s body know when it is time to give birth [5].

While agroclavin and other ergot alkaloids inflict devastating effects on mammals at standard temperatures, studies show that extreme temperature changes can render these substances even more toxic for horses and cattle [5,7]. Notably, when extreme heat or cold stress causes ergot alkaloids to become toxic to livestock, they may induce a neurological and biochemical process termed fescue toxicosis [5, 7]. Fescue toxicosis is a dangerous condition characterized by changes in blood flow and necrosis, or death, of fat cells in livestock [4]. Studies show that horses are more resistant to fescue toxicosis and the detrimental effects of ergot alkaloids than other herbivores, such as cattle, sheep, and rodents [4].

As temperatures continue to rise, some animals will suffer the adverse effects of volatile alkaloids more than others. While scientists are attempting to develop non-toxic fungi for grasses eaten by livestock as a potential solution, ergot alkaloids form only a small portion of the toxic PSCs that are harming herbivores at alarming rates [5]. Since livestock are commercially important, it is vital to prevent PSC poisoning. Without the costly funding of innovative treatments, other herbivores will need to adapt and fend for themselves.

Foul Tastes: Marsupials and the Detection of Toxic Jensenone

Imagine that you are dining on your favorite dish at your favorite restaurant. It’s a meal you have eaten dozens of times; as you pick up your fork, your mouth waters in anticipation. However, when you arrive home, you proceed to spend the next four hours violently vomiting. You have come down with food poisoning. When a certain food makes us sick, we often feel a strong aversion to it for months or even years after consuming it. This phenomenon, known as conditioned taste aversion, is a survival mechanism that trains our bodies to avoid damaging substances before they can cause us harm [8]. Taste aversions occur in many different mammal species, and studies have shown that some herbivorous marsupials use them to minimize the ingestion of toxins.

Common brushtail possums, ringtail possums, and koalas are marsupials that consume large quantities of Eucalyptus leaves. Eucalyptus contains jensenone, an organic compound that can cause damage to the marsupials that consume it. When marsupials eat jensenone, it binds to molecules in their gastrointestinal (GI) tract, disrupting metabolism and leading to symptoms such as nausea, anorexia, and malaise [9]. This is because, before it can be metabolized or sequestered to other tissues, jensenone conjugates (or combines with) various compounds that stimulate serotonin 5HT receptors [9, 10]. Serotonin is a neurotransmitter commonly found in GI tract cells and is responsible for modulating a variety of bodily functions, including mood and appetite. However, excess concentrations of serotonin in the GI tract can induce nausea and vomiting by stimulating the vagus nerve and causing the abdominal muscles and diaphragm to contract [9, 10]. The vagus nerve runs directly from the brain to the digestive system and regulates many essential bodily functions, including heart rate, digestive movements, and the gag reflex. Similarly to how we become averse to certain foods after they make us vomit, marsupials develop a transient aversion to jensenone compounds after they stimulate nausea [8]. These taste aversions may play a role in how common brushtail possums — and other animals — determine and mediate toxin levels in their diets.

A Picky Eater: The Selective Diet of the Common Brushtail Possum

In the past few years, researchers have investigated how exactly toxin concentration interacts with the foraging choices of various herbivorous mammals. One study asked whether the common brushtail possum alters its feeding behavior in order to increase its capacity to detoxify benzoic acid, a common PSC [11]. Possums are known to conjugate jensenone with amino acids in order to metabolize them more rapidly [11]. By extension, scientists theorized that possums may select diets that help detoxify other PSCs faster [11]. Furthermore, researchers questioned whether possums are capable of recognizing excess toxin amounts in their diets, triggering nausea and vomiting in response [11]. This same study also found that the amount of food possums could eat varied, depending on how quickly they could detoxify PSCs in their diet [11]. By altering their diets to break down toxic compounds faster, possums can potentially eat larger amounts of food and obtain more nutrients.

Scientists have sought to expand upon research concerning diet selection by studying marsupial feeding habits in more realistic environments. Specifically, more recent studies account for other environmental variables, such as predation risk and varying toxin concentrations in plants [12]. In a 2011 study, researchers performed an experiment in which possums chose between a non-toxic food in a risky predation region, or foods with one of five varying toxin concentrations at a safe predation region [12]. The study showed that if toxin amounts increased in food found in the safe areas, possums would start migrating to riskier areas to feed [12]. In another study, the interplay between predation risk and plant toxin effects on food intake was similarly tested, and results confirmed that both factors influence possum foraging behavior [13]. These findings suggest that some herbivores are capable of analyzing and comparing two different costs when feeding, similar to the cost/benefit analyses we might perform before making an important decision. The animals then adjust their feeding behavior to respond to the apparent risks.

As increasing temperatures begin to alter the nutrient composition of plants, the brushtail possum’s ability to select its diet may prove useful in its ability to adapt to changing nutrient availability. However, warmer temperatures may have devastating effects on all herbivores and their abilities to metabolize PSCs, regardless of their feeding behavior.

The Heat Dissipation Limit Hypothesis: Trouble For Herbivores

If you pass by a lake or a stream on a sweltering summer day, you might see a lizard cooling itself on a shady rock or a snake slithering underneath a dark bush. Reptiles like lizards and snakes are known as ectotherms, meaning they use external sources, such as a warm rock or a patch of cool grass, to regulate their body temperatures. In contrast, all mammals are endothermic, meaning that they generate and regulate their body temperature internally when they expend and generate energy. A significant portion of energy expenditure in mammals occurs through routine bodily functions, such as liver metabolism. In fact, liver metabolism is responsible for nearly 25% of heat production in mammals [14]. Scientists posit that any kind of energy expenditure generates heat, which poses a risk of hyperthermia, a potentially deadly condition in which an animal’s body absorbs more heat than it is capable of dissipating [14]. Therefore, animals are constrained in their ability to expend energy [14]. This theory is referred to as the heat dissipation limit hypothesis [14]. Studies show that for herbivores, metabolizing toxic PSCs in the liver results in increased heat production [14]. If PSC detoxification increases body heat to the point where the animal can no longer dissipate it, hyperthermia may occur. To account for these dangerous increases in body heat, liver metabolism slows which causes the animal’s ability to break down toxic PSCs to decrease. [14].

Further research suggests that PSC toxicity may be related to the interplay between the animal’s body temperature and that of the environment. In one study, scientists investigated woodrats that consumed juniper, a tree containing high levels of toxic PSCs [2]. Researchers found that body temperatures of woodrats that consumed a juniper-containing diet at a higher temperature were higher than body temperatures of woodrats that consumed a juniper-containing diet at lower temperatures [2]. These findings may suggest that as temperatures increase, other PSCs, in a similar fashion to juniper, may be more harmful to herbivorous mammals at warmer temperatures. Researchers have determined that PSCs take a significant amount of energy to detoxify and can cause neurotoxicity or disrupt nutrient intake. Therefore, studying the mechanisms that herbivores have evolved to detoxify and cope with plant toxins is imperative to understanding how exactly climate change is rendering PSCs more toxic.

Implications for Other Herbivores

In the past decade, a theory has emerged regarding how herbivore livers detoxify PSCs. Think of the liver as a large wastewater treatment plant. As polluted water enters the facility, various different filters sort out and break down the largest and most visible pollutants. The polluted water then continues through the facility as the pollutants are gradually purged from the system. Scientists theorize that when a brushtail possum consumes a variety of PSCs, different compounds are metabolized in distinct detoxification pathways at the same time [15].

Dose-dependency -- the relationship between the amount of a substance consumed and its effects -- may also play a role in herbivore diet selection [8, 16]. For instance, if the effects of a drug increase with gradually higher doses, that drug would be considered dose-dependent. When herbivores experience harsh post-ingestive consequences, such as nausea or vomiting, they will be more inclined to avoid eating the food that resulted in the negative result. This passing avoidance behavior is termed a transient aversion. Animals that eat less of diets with high jensenone concentrations are conditioned to develop more detrimental post-ingestive effects, due to the ingestion being an irregular occurrence [8]. This finding suggests that aversions to toxic compounds in herbivores are a conditioned response rather than a physiological inability to detoxify PSCs. Therefore, there is likely a degree of plasticity involved in a herbivore’s ability to cope with changing concentrations of toxins in their environment, via acquired behavioral responses such as taste aversions. In all, knowledge of these underlying biochemical and neurological mechanisms is critical to understanding how foraging herbivores navigate diet choices.

Furthermore, evidence suggests that specialist and generalist herbivores may differ in their ability to process toxic PSCs. Studies show that specialist herbivores, which consume a very narrow range of food sources, may detect PSCs more quickly than generalists that eat a wide variety of different foods [17]. On the other hand, generalists, such as the brushtail possum, proved to be far more capable than specialists at regulating and adjusting their meal sizes to respond to PSC levels in food. Since specialist herbivores struggled to modulate their PSC consumption, they experienced more cell and nerve damage [17]. In other words, global warming could impact generalist and specialist herbivores at different rates, based on the species’ ability to recognize and process the changing amounts of toxins in their food.

Food For Thought

Currently, research regarding how elevated temperatures affect PSC toxicity is still in its infancy. While evidence shows that some herbivores can adapt to cope with toxins, others may struggle to alter their feeding behaviors. The effects of rising temperatures on PSC toxicity are quite complex, and tackling this crisis will require a better understanding of how animals regulate their food intake and detoxify PSCs. Conducting comprehensive research on these topics is urgent. Although the crisis of global warming will eventually impact all life on Earth, herbivores appear to be particularly susceptible to its ravages. As temperatures rise, herbivorous mammals including livestock, mice, voles, possums, and many other animals will continue to experience the effects of temperature-dependent toxicity.

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