Prions: A Protein Becomes Infectious - and Resists Almost Everything

2 days ago
10 min read

In 1984, Stanley Prusiner, a researcher at the University of California San Francisco, proposed something that seemed impossible. The cause of certain brain diseases was not a virus, not a bacterium, not a fungus. It was a protein. A misfolded protein. A protein with no genetic material of its own, yet capable of infection. A protein that could cause other proteins to misfold, creating a self-propagating cascade of disease. The scientific establishment rejected this idea. Infectious particles required nucleic acids: DNA or RNA. They required genetic material to replicate. A protein alone could not be infectious. It violated central dogma.

Yet Prusiner was correct. The disease was scrapie, afflicting sheep and goats for centuries. The infectious agent was a prion, a misfolded protein. Prusiner's revolutionary work, which won him the Nobel Prize in Physiology or Medicine in 1997, established that prions were real, transmissible, and capable of causing incurable neurodegenerative disease.

Today, prions are recognized as agents of multiple human and animal diseases. Scrapie in sheep and goats, Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (mad cow disease) in cattle, and chronic wasting disease in deer are all prion diseases. In June 2026, goats tested positive for scrapie, highlighting the ongoing threat these diseases pose.

Understanding prions requires understanding what they are, how they function, how they spread, and why they are so difficult to eliminate.

Misfolded Infectious Proteins

A prion is an infectious protein particle. Prions are composed entirely of protein, with no nucleic acids (DNA or RNA). This distinguishes prions from all other infectious agents, which contain genetic material. The normal prion protein is called PrP or PrP-C (C for cellular). This protein is produced naturally in the brains of mammals and other animals. The function of the normal prion protein is not entirely understood, but it appears to play a role in cell-to-cell communication and possibly in maintaining the health of neural cells. Most animals and humans have normal prion proteins in their brains. The normal prion protein is harmless.

However, under certain conditions, the prion protein can misfold. Instead of folding into its normal three-dimensional shape, it folds into an abnormal shape. This abnormally folded prion protein is called PrP-Sc (Sc for scrapie-associated). The abnormal form is infectious.

The key insight is that the abnormal prion protein can cause normal prion proteins to misfold into the same abnormal shape. This creates a chain reaction. One misfolded protein causes another normal protein to misfold. That protein causes another to misfold. The reaction propagates through the brain, converting more and more normal prions into the abnormal form.

This self-propagating cascade is unique to prions. No other protein is known to work this way. Most misfolded proteins are simply degraded by the body's cellular machinery. But prion proteins resist degradation. They accumulate. They form aggregates. They spread throughout the brain.

Brain Sponging and Neurodegeneration

As abnormal prion proteins accumulate in the brain, they cause damage. The exact mechanism by which prion protein misfolding damages neurons is still being researched, but the consequence is clear: the brain develops progressive, irreversible damage. The brain tissue becomes sponge-like, with holes appearing throughout the neural tissue. This spongiform appearance, sponge-like, is why prion diseases are called transmissible spongiform encephalopathies. The brain literally becomes porous and damaged. Neurons die. Brain tissue deteriorates. The damage is progressive and unstoppable. There is no known way to stop the cascade once it begins. There is no treatment. There is no cure.

The symptoms depend on which brain regions are affected, but they typically include dementia, behavioral changes, loss of coordination, paralysis, and ultimately death. The disease progresses relentlessly. The incubation period—the time between infection and symptom onset—can be months to years, even decades in some cases. But once symptoms appear, the disease progresses rapidly. Prion disease is 100% fatal once symptomatic.

Prion Diseases in Animals: Scrapie, Mad Cow, Chronic Wasting Disease

Multiple prion diseases affect animals. Scrapie, the disease that gave the abnormal prion protein its name (PrP-Sc), has afflicted sheep and goats for centuries. The disease causes intense itching; hence the name. Affected animals compulsively scrape and rub against objects. Neurological symptoms develop. Death follows.

Scrapie exists in two forms: classical scrapie and atypical scrapie. Classical scrapie is transmissible and has been documented for centuries. Atypical scrapie is a more recently recognized form that may arise sporadically.

Bovine spongiform encephalopathy, commonly called mad cow disease, emerged in cattle in Britain in the nineteen eighties. The disease spread through cattle herds, causing epidemic illness and death. The disease is believed to have spread through contaminated feed—cattle were being fed remains of other cattle, which transmitted prions. Humans who consumed beef from infected cattle developed variant Creutzfeldt-Jakob disease. The epidemic killed hundreds of people before regulations preventing the feeding of cattle remains to cattle were implemented.

Chronic wasting disease affects deer and elk in North America and has spread across multiple states and regions. The disease causes weight loss, behavioral changes, and death. The disease appears to spread through environmental contamination and direct contact between animals.

Prion Diseases in Humans

Humans can develop prion diseases. The most common is Creutzfeldt-Jakob disease, or CJD. Classical CJD occurs sporadically, meaning it arises without known exposure. The disease affects approximately one person per million per year globally. It strikes without warning, progresses rapidly, and is invariably fatal. Variant CJD emerged in Britain in the nineteen nineties as a consequence of consuming beef contaminated with mad cow disease prions. This form of CJD is particularly tragic because it resulted from human consumption of contaminated food. The outbreak was large by prion disease standards—hundreds of people died—but small compared to the number of people exposed. Most people who consumed contaminated beef did not develop the disease, suggesting genetic factors influence susceptibility.

Familial CJD is an inherited form caused by mutations in the prion protein gene. People with these mutations can develop CJD.

Kuru is a prion disease that emerged among the Fore people of Papua New Guinea. The disease spread through ritual cannibalism—specifically, women and children consuming the brains of deceased relatives as part of funerary practices. The disease caused progressive neurological decline and death. When cannibalistic practices ceased, the disease disappeared, though cases continued to occur due to the long incubation periods of survivors.

Transmissibility: How Prions Spread

One of the most alarming aspects of prions is their transmissibility. Prions are infectious and can spread between animals and, in some cases, between species. In sheep and goats with scrapie, transmission occurs primarily through exposure to placenta and birth fluids from infected animals. Pregnant infected sheep or goats shed prions in placental tissues and uterine fluids. Young lambs or kids can become infected by ingesting these materials. This vertical transmission, from infected mother to offspring, has been documented as the primary transmission route in classical scrapie.

Recent research in 2026, following goat testing for scrapie resistance, confirms that transmission can also occur through milk from infected goats. Lambs fed milk from scrapie-infected goats became infected with scrapie prions. This demonstrates an additional transmission route beyond placental exposure.

Environmental contamination is a significant concern. Scrapie prions can persist in soil for years. Pastures previously grazed by infected sheep remain contaminated and capable of transmitting prions to newly introduced susceptible sheep, even years after the original infected animals have been removed.

Equipment and objects can harbor prions. Research has demonstrated that troughs, fencing, and other farm equipment used by infected sheep can transmit scrapies to susceptible sheep placed in contact with the contaminated objects.

Recent evidence from chronic wasting disease in deer suggests that infected animals shed prions in saliva and feces. This makes environmental transmission easier because animals need not consume infected tissue directly. They can become infected through contact with contaminated saliva or feces in the environment.

Prions are highly resistant to standard disinfection procedures. Bleach does not reliably kill them. Boiling does not reliably kill them. Autoclaving (high-temperature, high-pressure sterilization) can reduce prion infectivity but may not eliminate it entirely. This resistance to disinfection makes prion contamination particularly problematic. Once an environment is contaminated, decontamination is extremely difficult.

Genetic Susceptibility: Why Some Animals Resist Infection

Despite the transmissibility of prions, not all animals exposed to prions develop disease. Genetic factors influence susceptibility. The prion protein gene, called PRNP in humans and similar names in animals, contains variations called alleles.

In sheep, susceptibility to scrapie is determined by PRNP genotype. Sheep with certain genotypes are highly susceptible. Sheep with other genotypes show resistance. The genotypes associated with resistance were identified through studying sheep that were exposed to scrapie prions but never developed disease.

In goats, genetic resistance has been more recently recognized and characterized. In June 2026, the USDA and goat breeders were testing for scrapie-resistant alleles. Three alleles have been identified: S146 (serine at position 146), D146 (aspartate at position 146), and K222 (lysine at position 222). Goats carrying even a single copy of one of these resistant alleles show substantially reduced susceptibility to classical scrapie infection. This genetic understanding opened the possibility of breeding sheep and goat herds for resistance. By selectively breeding animals that carry resistance alleles, farmers can reduce the prevalence of scrapie in their herds over time. Genetic-based breeding programs have been implemented in some countries with remarkable success.

In humans, the prion protein gene also shows variation. Certain genotypes are associated with higher susceptibility to Creutzfeldt-Jakob disease and other prion diseases. This may explain why some people exposed to prions develop disease while others do not.

Recent Testing for Scrapie Resistance

In June 2026, the USDA announced that genetic testing for scrapie-resistant alleles would become available for goats. This represented a major development in prion disease control, paralleling similar genetic testing programs that had already proven effective in sheep. The testing allows goat breeders to identify animals carrying resistance alleles S146, D146, or K222. Goats with even one copy of a resistant allele show much lower susceptibility to scrapie infection. Homozygous animals (carrying two copies) are believed to be highly resistant, though few such animals exist to confirm this. The genetic testing program offers promise for reducing scrapie in goat herds through selective breeding. Over generations, herds can be shifted toward genetic resistance. However, the long incubation period of scrapie means that the results of breeding programs take years to manifest in herd health. The testing also reflects ongoing concern about scrapie in goat populations. The disease remains a threat. Vigilant monitoring, testing, and breeding for resistance are essential to controlling it.

Prions That Won't Die

One of the most troubling aspects of prions is their environmental persistence. Prions can survive for years in soil, on equipment, and in contaminated materials. Research has shown that scrapie prions bind to soil particles and remain potentially infectious when excavated from soil years after initial contamination. This means that once a pasture is contaminated, it remains contaminated indefinitely unless subjected to extreme decontamination procedures.

Equipment and buildings used by infected animals pose ongoing transmission risks. Thorough cleaning with harsh chemicals helps but may not fully eliminate prions. Some facilities that previously housed infected animals must be abandoned or subjected to extremely aggressive decontamination procedures to be safely used again.

This persistence means that prion disease poses a long-term environmental hazard. A single infected animal can contaminate a farm, making it dangerous for subsequent animals unless extensive decontamination is performed.

Detection and Diagnosis

Detecting prions is challenging. During the incubation period, infected animals show no symptoms. They may carry prions and shed them into the environment, but standard health examinations reveal nothing abnormal.

Brain biopsy or autopsy, examining brain tissue microscopically for characteristic spongiform changes and abnormal prion protein accumulation, is the gold standard for prion disease diagnosis. However, this is invasive (for biopsy) or only possible after death (for autopsy).
Blood tests for prion disease have been developed and are improving. These tests can sometimes detect prion disease in blood before symptoms appear, offering hope for antemortem (before death) diagnosis.
Environmental and tissue testing can detect the presence of prion proteins. Serial protein misfolding cyclic amplification (sPMCA) is a laboratory technique that can detect minute quantities of misfolded prion protein in samples. However, detection methods are not yet as sensitive or practical as public health officials would prefer.

Prevention and Control

Controlling prion diseases requires preventing transmission. This involves multiple strategies.

Breeding for genetic resistance is one effective approach. Identifying and selecting animals carrying resistant alleles reduces the frequency of susceptible animals in herds. Over time, resistant herds can be established.
Preventing contamination requires careful management. Infected animals should be removed from herds. Equipment should be disinfected or replaced. Pastures should be rested and restocked with genetically resistant animals.
Feed safety is essential. Preventing the feeding of cattle remains to cattle (or of other livestock remains to susceptible species) reduces transmission risk.
Quarantine and testing of animals from potentially exposed sources can help prevent introduction of prions into clean herds.
Biosecurity measures including separate equipment, dedicated clothing, and hygiene protocols can reduce transmission risks in facilities working with multiple animal groups.

The Bottom Line

Prions are misfolded proteins that cause the most terrifying of diseases: transmissible spongiform encephalopathies that are incurable, untreatable, and universally fatal once symptomatic. A single prion protein, by forcing other normal proteins to misfold, creates a self-propagating cascade of disease. Scrapie in sheep and goats, mad cow disease in cattle, chronic wasting disease in deer, and Creutzfeldt-Jakob disease in humans are all consequences of prion infection.

Prions are transmissible through direct contact with infected tissue, through environmental contamination, through placental and milk transmission, and through contaminated equipment and soil. They resist boiling, bleach, and standard disinfection procedures. They persist in the environment for years. Yet genetic resistance offers hope. By breeding for scrapie-resistant alleles, as goat farmers in the United States began testing in June twenty twenty-six, herds can be made resistant to prion disease over time.

Understanding prions illuminates how a single protein can cause infectious disease. It demonstrates that infection need not involve nucleic acids. It reveals how natural selection shapes genetic resistance to disease. And it reminds us that despite modern medicine's many achievements, some diseases remain incurable, making prevention the only viable strategy.

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