Brain tissue from a cow infected with mad cow disease. The bubble-like holes are formed by death of brain tissue.

When nights become longer and Halloween draws near, it is a good time to reflect on some of the more frightening aspects of science and the world around us. One of those frightful aspects that we’ve all become all too familiar with in the past few years is disease. Most diseases that affect humans are bacterial or viral in nature, though a few might be caused by fungus or parasites. Far less common are those caused by particles as insidious as they are poorly understood: Prions.

A prion is a protein, one that is identical to proteins already functioning healthily in the body, but for one respect: It is misfolded. How a protein is folded determines its shape and purpose. Small changes in protein shape can cause a protein to stop functioning. Normally, damaged proteins are swiftly broken down by cells. Prions are able to evade these degradation mechanisms, and their effects on the body are as shocking as they are unique.

When a prion encounters a healthy protein, it interacts in a way that causes the normal protein to change configuration and take on the misfold of the prion. This is the start of a chain reaction. More and more proteins interact with the multiplying prions and are misfolded. These prions will often link together and form chains, eventually clumping together in conglomerations known as amyloids.

Amyloids cause cellular death in the brain, and once the cascade of destruction has begun, it is impossible to stop. No prion disease has a cure, though in some cases medication can slow the spread. One disease caused by prions is called kuru, and by the time symptoms appear, death is guaranteed.

Kuru

Kuru is a disease with a fascinating history. It has only ever been diagnosed in Papua New Guinea, in the villages of the Fore people. At the time of its discovery in the 1950s, about 200 people per year were dying in a population of around 11,000. The mysterious illness primarily affected women and children, and clustered among social groups, sometimes killing entire circles of relatives or close companions over the course of a few years.

Doctors identified three stages in the kuru disease: Ambulant, sedentary, and terminal. In the first stage, ambulant, those infected developed tremors, an unsteady gait, and balance issues. They had issues pronouncing words, and a general decline in muscle control. Symptomatic patients were still able to function fairly normally in this stage.

Their symptoms would grow more severe in the sedentary stage, which saw sufferers lose the ability to walk without support. This is when the emotional and cognitive effects of kuru become more apparent. People often become depressed and emotionally unstable, but will burst into uncontrolled laughter periodically.

In the final part of the process, the terminal stage, the brain damage becomes so severe that personality begins to fall away. Patients are often awake, but unresponsive. They are no longer able to sit on their own, and progressively lose the ability to swallow and speak. Death often occurs due to malnutrition, or from complications resulting from ulcerated wounds.

Kuru was a tragedy for the Fore people. In some villages, so many women died from the disease that survivors worried their village would become extinct within a generation. They could do nothing but comfort their loved ones as kuru ate away at their minds, bodies, and spirits. The scientists studying kuru were perplexed. Where was the disease coming from, and why did it primarily impact women and children? When the cause was discovered, it was surprising, and yet explained perfectly the pattern in what they were seeing.

The misfolded protein that causes kuru. To the right is the chain of misfolded proteins, linked together. Image by Kupfer, L; Hinrichs, W; Groschup, M.H.

The Origin of Kuru

It was one particular cultural practice that spread kuru: Funerary cannibalism. It was considered cold and uncaring to leave loved ones to rot and be eaten by the worms of the earth or insects of the land. They would cook the bodies of the deceased, and at the funeral together ate the body as a final act of affection and grief.

It was believed that the disquiet soul of the deceased resided primarily in the brain. Women, considered superior at quieting a distressed and sometimes angry ghost, cooked and ate the brain, sharing it with children of the village. Unfortunately, the brain is exactly where kuru is found in greatest concentration, and cooking does little to reduce prion infectiousness.

Once the connection between cannibalism and kuru was discovered, the practice of funerary cannibalism was brought to an end. Cannibalism had ceased in Fore villages by the 1960s, but it wasn’t until 2009 that the final person known to be infected with kuru passed away. This is due to a variable incubation period. Kuru primarily appears between 10 - 13 years after consumption of contaminated material, but can lie in wait for as long as 50.

Thankfully, it seems likely that we have seen the last of this fatal prion disease. However, the defeat of one particular prion doesn’t mean that we are safe from the rest of them.

A cow showing loss of weight and odd posture consistent with mad cow disease

Prion diseases are highly uncommon and generally only spread under very specific conditions, but there are several of concern. One of the most prominent prion diseases currently is mad cow disease, or bovine spongiform encephalopathy (BSE). It spreads from cow to cow via eating feed containing products contaminated with infected cow tissue.

BSE is one of the only prion diseases capable of spreading from animals to humans, and humans can become infected if they eat brain or spinal material from a sick cow. Sometimes the meat alone is enough to transmit infection. Over 200 people have caught BSE, and the disease progresses in a very similar (and just as fatal) manner as kuru.

Chronic wasting disease (CWD) is seen among the deer family of North America. We are very lucky that it isn’t able to jump species as BSE does. Unlike most prion diseases, CWD doesn’t require consuming infected tissue to spread. Deer can become infected by coming into contact with saliva, urine, feces, or other bodily fluids from infected deer. This enables CWD to spread much faster and farther in a population than most prion diseases, yet frighteningly, it remains just as deadly and incurable as others.

If a prion disease capable of infecting humans that spread via bodily secretions ever appeared, we’d be in trouble. Prions are extremely resistant to typical decontamination methods. They can survive for years on dry surfaces and still be infectious, and resist both heat decontamination and protein-cleaving enzyme degradation. Sterilizing surgical tools contaminated by prions is exceptionally challenging, which has caused spread of prion disease among brain surgery patients in the past.

It is possible to destroy prions using a strong base, or a longer time spent at high heat, but it is hard to imagine how one could ensure a bathroom were free from prions if a disease that spread through urine, feces, or blood appeared. We are lucky that this is not a concern so far, and it is only by keeping a watchful eye on emerging diseases that we can prevent it from occurring in the future. For now, prion illnesses remain one of the less understood, but most fatal, diseases ever to be encountered by humankind.

Kate Dzikiewicz, Science Curatorial Associate