How did the domino-like "brainless movement" spread from cows to humans?

In October 1986, in the town of Alford in southeast England, a cow suddenly fell to the ground, convulsed, and foamed at the mouth. After struggling in pain for several days, it died miserably.

The veterinarian who heard the news told everyone that this mysterious disease had been raging among cattle all over the UK for more than a year, but no one knew what caused the disease or how it spread. It was like a Grim Reaper playing with the world, arbitrarily harvesting cattle all over the UK.

Because the infected cows show various symptoms of mental disorder, people call this strange disease "Mad Cow Disease".

From mad cow to patient

In order to resist this strange plague, people drove whole pens of cattle into the wilderness, killed them, minced them into paste, and then threw them into a 1000℃ high temperature incinerator. But even so, people were powerless to stop the mysterious disease from killing people all over Britain. The real nightmare had just begun here.

In 1995, in Edinburgh, England, a young man developed the same symptoms as those of the "mad cow". He was mentally confused, incoherent, had a distorted expression, behaved strangely, and eventually died slowly in convulsions.

Starting with him, hundreds of similar patients appeared in the UK in just a few years. Doctors called their symptoms variant Creutzfeldt-Jakob disease (vCJD). The common feature of these patients is that they have eaten sick beef suspected of containing mad cow disease. Obviously, some strange pathogen was transmitted from mad cows to humans through meat.

Both mad cow disease and Creutzfeldt-Jakob disease have an incubation period ranging from a few months to several years, and at the time there was almost no way to detect whether cows or humans were already sick in vivo.
For a time, people were in a panic. Ranchers suspected that their cattle were carrying diseases, and the British, who had long been eating their own beef, fell into great fear. Internationally, British beef was condemned by everyone, and the UK, once a beef exporter, even began to spend 3.5 billion pounds a year to import beef.

But this did not stop the mysterious disease from spreading around the world. In the following decade, reports of mad cow disease or variant Creutzfeldt-Jakob disease appeared in France, Spain, the United States, Canada, Saudi Arabia, Myanmar, Japan and other countries.

Scientists and doctors from all over the world are just as worried as the people and governments in the infected areas. Autopsies of patients and animals have found that the brains of the deceased have become riddled with holes, and look like sponges under a microscope. It is this lesion that causes a series of mental and behavioral symptoms in patients. Therefore, mad cow disease, variant Creutzfeldt-Jakob disease and other related diseases are collectively referred to as spongiform encephalopathy.

As the tests went deeper, scientists discovered that a highly recognizable protein polymer always appeared in the brains of these deceased people. At that moment, people recalled an extremely unpopular pathogen - prion.

Zombified Protein

Prions are perhaps the most bizarre and mysterious infectious agents known to man, and they have been known to humans since before the mad cow disease incident.

In the 18th century, German farmers found that some sheep would become crazy. They seemed to be itchy all over, and would desperately rub their backs with objects such as wooden stakes, and then become listless and starve to death. They found that this disease was also contagious. If the sick sheep were not isolated, it could cause serious infection in the entire flock. The locals called it "Scrapie".

In 1982, American neuroscientist Stanley Benjamin Prusiner isolated a previously unheard-of pathogen from the brains of sheep suffering from scrapie.

This pathogen is neither a bacterium nor a virus, but a pure protein molecule without any genetic material such as DNA or RNA. He named this pathogen "prion". However, the name prion can easily lead people to mistake it for a virus, so some scholars suggest translating it into prion particles or prion bodies - please note that prion is not a pathogen, but a general term for a large class of proteins.

It is somewhat mysterious why a mere protein molecule can cause such a big storm in the brain.

Prions themselves are not toxic, but they have a special way of spreading. In layman's terms, they are zombies at the molecular level. Take mad cow disease as an example. If the prions of mad cow disease come into contact with a protein called PrP in the human brain, there is a chance that the latter will transform from an ordinary working protein into a prion similar to itself. These PrP proteins that have transformed into prions will never be calm again, and they will frantically transform other ordinary PrP proteins into prions.

Generally speaking, any cell has a mechanism to deal with abnormal proteins, but under the saturation attack of the rapidly proliferating prion zombies, this mechanism will be quickly exhausted. What's worse is that prions like to gather together to form huge prion polymers, which not only increases the difficulty of degrading these abnormal proteins, but also seriously interferes with cell activities and eventually kills the nerve cell where it is located.

The horror story is not over yet. After the nerve cells die and lyse, the prions in them will also escape and infect the surrounding nerve cells. As a result, the nerve cells in the brain will fall one by one like a fortress against zombies in the apocalypse - the bad thing is that nerves are almost non-regenerative, and once dead, they are dead. In the end, a large number of nerve cells lyse, holes are opened in the brain, and the host animal cannot escape death.

Because the PrP and other proteins in each person's or cow's brain are somewhat different, coupled with some other factors, their ability to fight prions varies from bronze to king. This is why, facing the same infection conditions, some individuals are invincible, while others are safe and sound.

Where does this pathogen that can open up the brain come from?

Mystery of origin

Since prions have no genes, their continuation depends purely on damaging other proteins, which is a wild way of spiritual inheritance. The molecular biology tools generally used to trace their origins are useless. Therefore, people can only look for clues from other aspects.

Currently known prions almost always work in the nervous system, which provides a key clue to revealing the origin of prions. In fact, many neurological diseases will have a large number of nerve death phenomena similar to spongiform encephalopathy. For example, the root cause of Alzheimer's disease (commonly known as senile dementia) is the large-scale death of memory-related neurons, and the typical feature of Parkinson's disease is the collapse of some nerve cells in the brain that are responsible for transmitting motor signals.

As scientists delve deeper into these diseases, they have discovered that there are always some abnormal proteins at work. In familial Parkinson's disease, a protein called alpha-synuclein plays a key role. The alpha-synuclein in the brains of patients with familial Parkinson's disease occasionally spontaneously misfolds, and the deformed alpha-synuclein has a certain chance of inducing similar misfolding of normal proteins of the same type.

Not only that, these misfolded α-synuclein proteins will aggregate into clumps and eventually kill neurons. As neurons break down, these deformed α-synuclein proteins will be absorbed by surrounding neurons, triggering a domino-like "brain-damage movement".

This scenario is very familiar. As research deepens, more and more proteins with similar characteristics are discovered, and they are often the culprits behind some neurological diseases.

The answer seems to be obvious.

The only problem is that these proteins are often very fragile and quickly lose their activity once they leave the brain environment. Only by injecting the brain of a sick animal directly into the brain of another animal can there be a small chance of them spreading between different individuals.

However, in the face of the violent exhaustion of evolution, all problems, as long as they have solutions, are destined to be solved one day.

In Papua New Guinea, some tribes often suffer from a strange disease. Patients first suffer from headaches, joint pain, and tremors in their limbs, then gradually develop schizophrenia, amnesia, and eventually die in laughter. This is called "Kuru" by the locals. The transmission of Kuru disease depends on the local indigenous people's habit of eating the corpses of their deceased relatives. Later, people discovered that the culprit of Kuru disease is also misfolded PrP protein, but it is not exactly the same as PrP that causes mad cow disease.

Perhaps it was during the long process of evolution that proteins that were able to survive for a short period of time outside the brain environment, and even resist digestion and penetrate the digestive tract and blood vessel walls, evolved into later prions.

It is important to note that prions are the result of misfolding of normal proteins, and cannibalism is not the cause of prions. Cannibalism may be one of the ways prions spread, but not all prions spread through cannibalism. Many prions also have other ways of transmission, such as sheep scrapie, which is generally transmitted through body fluids.

When natural laws meet human madness

The story should have ended here, but unfortunately human greed and unscrupulousness have written an even darker chapter.

Logically speaking, prions are just proteins. They cannot remain dormant like bacteria, nor can they crystallize like viruses. Their ability to spread is ultimately limited - unless there is human intervention.

Since the 1980s, the UK has widely used the brains, bones, and internal organs of cattle and sheep that are not eaten by local people to make so-called "feed supplements" for cattle and sheep. Unfortunately, the health department's supervision of feed is much lower than that of human food, so some sick animals carry various prions. This artificial "cannibalism" has turned the entire British pasture into a place for prions to breed.

Some people speculate that perhaps in just a few years, various prions circulated among different cattle and sheep, constantly training various proteins in their brains to transform into new prions, just like various MLM organizations holding an experience exchange conference. In the end, a prion that can be transmitted across species emerged, and this is the mad cow disease we mentioned at the beginning.

The mutated Creutzfeldt-Jakob disease epidemic that began in the 20th century has infected hundreds of people worldwide and left countless people with psychological trauma that will be difficult to recover from for the rest of their lives.

Fortunately, governments destroyed suspected infected animals and products at all costs, and cooperated with stricter supervision, which eventually stopped the plague. Since 2014, there have been no deaths reported from variant Creutzfeldt-Jakob disease in the UK.

Maybe this time, people succeeded in destroying the zombies' bodies. But no one knows what form they will take next time, and once again take away healthy minds amid countless wails.