Prions! What are these dangerous little things?

 

The cover of the science fiction novel Aurora, by Kim Stanley Robinson. It includes a plot line about prions rendering a planet uninhabitable to humans.

I first heard about prions when I read the science fiction novel Aurora by Kim Stanley Robinson, which details the journey of a spaceship that successfully reaches another planet (yay!) where (spoiler alert!) there are prions that infect and kill the would-be settlers, rendering the new planet inhospitable. At first, the settlers are unable to figure out what is causing the illness. People seem to be getting sick and dying without any clear cause. Eventually, though, they figure out that a "prion-like organism" is the culprit. So, what exactly are prions? And how could they pose such a great threat to living things?

To start with, prions are generally understood to be misfolded proteins with the ability to transfer their misfolded shape to other proteins of a similar kind. The mechanisms of this shape transfer are not exactly clear, but there are studies being conducted to uncover the process by which proteins can be corrupted. Proteins are the very basic building blocks of living things, and their shape directly determines the functions they will have in a living thing. This shape is determined by the DNA of the organism, and the amino acid sequence that forms the different structures of the protein. All this is a bit complicated, and involves a lot of moving parts! The important takeaway is that proteins need to be functioning correctly for an organism to continue living without complications. When proteins are unable to respond to signals, catalyze reactions, or provide structure and support to the body, things begin to break down. 

A beautiful cow, which appears to be grass-fed, and has probably not ingested any dangerous prions. 

When there is a problem with the shape of a protein, and especially if that problem is spreading to more prion proteins throughout a part of the organism, the effects can be devastating. One disease you may have heard of is mad cow disease, also known as bovine spongiform encephalopathy (BSE). When cows consume feed that contains parts from another cow that was infected, the prion proteins can be taken into the body, where they slowly affect the brain tissue of the cow, causing it to take on a sponge-like texture. It takes several years for the disease to spread enough that it is noticeable in the behavior of the cow, but by the time they are having trouble walking or showing a change in demeanor, they are likely to die in the next few weeks or months. A concern for humans involved with managing and caring for these animals is that there is currently no way to test for BSE while the animal is alive. Luckily, it seems that prions cannot be transferred through bodily fluids or aerosols, like other kinds of diseases. 

Research so far has shown that prions appear to mostly cause neurological diseases in mammals, both humans and others. The diseases tend to have long incubation periods, sometimes several years, and result in degeneration of brain tissues and function, and eventually death. In this way, real-life prions are very different from those described in Aurora, which killed people within months. But before you get too worried, let me remind you that prion diseases, although almost certainly fatal, are extremely rare in humans. The most well-known and well-researched, Creutzfeldt-Jakob disease, occurs in only about one in a million people each year worldwide. Although unrelated to BSE, Creutzfeldt-Jakob causes a similar degeneration of the brain, including the characterization of a sponge-like texture in the brain tissue of those affected. 

A human brain with Creutzfeldt-Jakob has a sponge-like texture (image courtesy of the Centers for Disease Control and prevention)

A cow brain with BSE, also known as mad cow disease, which also exhibits sponge-like lesions (image courtesy of the Food and Drug Administration) 

Prion diseases, like the aforementioned Creutzfeldt-Jakob disease, the creatively named Variant Creutzfeldt-Jakob disease (vCJD), and others such as fatal insomnia, are divided into three subcategories: sporadic, genetic, and acquired.

Sporadic cases of the disease, also sometimes referred to as "classic" cases, do not have an identifiable cause, and the people affected do not have any known risk factors. This is the most common form of CJD, and it usually affects those over 60. Fatal insomnia is another sporadic prion disease, whose symptoms include insomnia and difficulty waking--it eventually leads to loss of consciousness and death. 

Genetic prion diseases are less common and occur either when a new mutation happens or when the gene for the malformed protein is passed down from the parents. In addition to familial CJD and familial fatal insomnia, this category includes Gerstman-Sträussler-Scheinker syndrome, an autosomal dominant change in a prion gene that usually exhibits itself in people aged 35-55. The disease progresses from lack of muscle coordination to more serious symptoms like dementia, blindness, deafness, and ultimately death. GSS syndrome is extremely rare and occurs in less than thirty families worldwide.

The final category, acquired prion diseases, describes diseases that occur when the person suffering from the illness acquired it through contaminated medical procedures, or from consuming meat that was contaminated. A variant of CJD in humans is thought to be caused by eating meat from a cow that had mad cow disease. An outbreak of this variant occurred in the United Kingdom in the 1980s and 90s and is thought to be caused by the use of animal remains in cattle feed, allowing prions to spread from the remains of an affected animal to a living cow, and then potentially to humans who ate the meat from that cow. 178 people died from eating the infected beef, and over four million cattle were subsequently slaughtered in an effort to control the outbreak. In the United States, the importation of British cattle was banned, and many recently imported cattle were slaughtered. Finally, the acquired prion disease Kuru reached an epidemic level in a tribe in Papua New Guinea that partook in cannibalistic rituals for the dead that involved eating their brain. The outbreak persisted until they ceased to perform those rituals. Acquired prion diseases are extremely rare in the global population, and the risk has drastically decreased as regulations are instituted and medical procedures are done in a more sanitary way. 

An image of some members of the Fore tribe, where the Kuru disease affected many people.

With all this information about how dangerous prion diseases can be, and how little we really know about them, it's easy to be disturbed or worried. Fear not! The risk of these diseases in humans is very low, and the likeliest thing is that you won't even know someone with one of these diseases in your lifetime. Additionally, there is some interesting new information from a research study by Stanford that suggests prions may also play a role in the inheritance of beneficial traits, and in evolution. Due to their ability to pass down traits to other proteins, prions can contribute to genetic variation, which is an essential part of evolution and the survival of a species. This study, in particular, focused on protein-based inheritance in yeast, but the information learned could be applicable to humans as well and could help further the ability of medical professionals to identify diseases and treat those who are ill.