In general, infectious diseases are caused by agents such as viruses, bacteria, fungi, and other organisms, which contain DNA or RNA. Therefore, it was a surprise when evidence began to mount that a group of brain and nervous system diseases known as transmissible spongiform encephalopathies were caused by much simpler agents — infectious proteins now known as prions (short for “proteinaceous infectious particles,” a term coined by Dr. Stanley Prusiner, who received a Nobel Prize for his work with prions). The now widely accepted “prion-only hypothesis,” suggesting that the proteins themselves were responsible for infection, went against the traditional understanding of disease transmission. Scientists are still attempting to pin down how prions work. Here is what we know, and don’t know, about these mysterious agents of disease.
The best-known prion diseases are bovine spongiform encephalopathy (BSE, or “mad cow disease”) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. These diseases have long incubation periods (years, in many cases), but once symptoms appear, they progress rapidly, leading to dementia, loss of muscle control, and death, often within a year. There is no cure for prion diseases.
How Prions Cause Disease
Prions are misshapen proteins which somehow induce normal proteins to change their shape. These altered proteins then alter the shape of others, causing a chain reaction in which abnormal proteins build up in the brain, creating plaques and killing nerve cells. As nerve cells die, visible holes develop in brain tissue, like the holes in a sponge (the “spongiform” part of transmissible spongiform encephalopathies).
Fortunately, prion diseases are rare in humans. A major mode of prion disease transmission is the consumption of infected tissue. One of the earliest documented prion diseases was kuru, which was found among tribes in New Guinea who ate infected human brain tissue during funeral rites. In the 1990s, a variant of CJD (vCJD) began to appear in people who had eaten meat from cattle infected with BSE. There is also evidence that prion diseases can be transmitted through infected blood and tissue used in transfusions and transplants.
Prion diseases have also been transmitted through contaminated medical instruments. It is difficult, if not impossible, to sterilize prion-contaminated objects, since prions resist the procedures normally used to destroy microbes. The Centers for Disease Control and Prevention recommends a combination of high heat and soaking in chemicals to sterilize prion-contaminated medical instruments; some instruments may simply have to be discarded.
A small percentage of prion disease cases can be inherited. The PRNP gene codes for a protein involved in the nervous system and other tissues, but a mutant form of this gene produces a misshapen, infectious prion. One such heritable prion disease is fatal familial insomnia, in which sufferers develop increasing insomnia and other nervous system dysfunction.
Prions are difficult to research. Their resistance to sterilization creates a safety issue in laboratories, and many methods for analyzing other molecules such as DNA do not work with prions. Many questions remain. Without DNA and RNA to transmit information, how do prions induce other proteins to take on abnormal shapes? Once they enter the body, how do these infectious proteins reach the brain? And finally, how can prion diseases be cured? Although prion diseases in humans are rare, knowing the details of how brain proteins become abnormal could lead to cures, not only for these diseases, but also for more common neurodegenerative diseases such as Alzheimer’s. Research on prion diseases continues to increase, but for now, the mysteries remain.