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As early as the 18th century, it is a miracle how people survived on their way to see a doctor. Many people don't. British pharmacies have bull penis, frog lungs and Egyptian mummies powder, which are obviously used to treat tuberculosis. Syphilis called "large pox" is treated with mercury. Don't mind if it makes you drool and eventually go crazy. John Brown, the Scottish doctor, author of "Elementa Medicinae", simply roasted beef, opium and wine for his patients. Many people think he is a genius.

Vaccination also appeared in this crazy period of trial and error. If you squint your eyes, it looks a lot like the early days of the Covid-19 outbreak, when desperate doctors were willing to prescribe any medicine to save their patients. What makes vaccines unique different? On the one hand, they are indeed effective. The most important thing about the Covid-19 vaccine story is how medicine evolved from a weird art to a rigorous science.

In the 18th century, one of the main diseases that doctors had to fight against was smallpox. It is a periodic scourge of mankind, and it has caused disfigured pustules on all those who unfortunately suffer from it. The most common form kills about a third of people, and those who survive sometimes become blind.

It is caused by a virus, but people at the time did not even know what a virus was. Around the world, long-term methods of preventing it include grinding the scabs of mild patients, and then inhaling it like snuff, or rubbing the wound on the skin, called macula. The mutation causes high fever, skin rash, and sometimes even death. Of course, it can protect a person from smallpox, but not everyone is willing to voluntarily infect themselves when there is no need.

In England in 1774, the village of Yeminster was facing a growing epidemic of smallpox, and smallpox was their only choice. A farmer named Benjamin Jesty lives with his wife, two boys and a baby girl in a stone house in the center of the village. Like many people in that era, he knew that female dairy workers often survived the smallpox epidemic unscathed. Jesty owns two female cow workers. Even though they took care of relatives who were affected by the disaster, they did not contract the disease. Previously, however, these women had reported pustules on the hands of the cows they were milking.

Jesty himself suffers from this mild infection called cowpox, which is caused by a virus closely related to smallpox, but his family does not. He grabbed a stocking needle-for knitting-and set off to find a herd of cows with vaccinia. He found them on the ranch of a man named Mr. Elford about 2 miles away. He bent down and poked one of the meek creatures at the wound on its breast. Then he turned to his wife and inserted the needle under her elbow. Her arm was swollen and she recovered after a week of fever.

He repeated this process with two young boys, 2 and 3 years old, and they performed better. Despite multiple epidemics in the village, Jesty's family has never contracted the disease. Fifteen years later, when a local surgeon vaccinated the boys with smallpox, they did not show any typical symptoms.

Jesty's story is just another folklore, until a few years later another person, Edward Jenner, finally unites the medical community around this concept. Like Jesty, he has also heard stories about milkmaid avoiding smallpox, but he is a doctor and is learning the knack of scientific methods. "Don't think, but try," his mentor told him. "Be patient and accurate." In 1796, he began testing the method on multiple subjects, including the 8-year-old son of a local worker. Instead of taking pus from the udder of a cow, he first took pus from the hand of a young woman with vaccinia lesions. It turns out that they are all protected by pus.

Jenner doesn't know exactly how or why it works, but he believes its potential is "essentially beneficial to humans." For a while, children were only vaccinated from arm to arm. Jenner will stick the vaccinia pus under the skin of a volunteer, and a week later, when a new blister erupts, he will retrieve it for the next person. Not the most hygienic method, it will cause syphilis and hepatitis outbreaks in the future. When Jenner wrote about his success, he called this method smallpox vaccine, which means vaccinia in Latin. But in the end, the term evolved to refer to all vaccines.

In the next two centuries, vaccinology has been known for being unscientific. In the middle of the 20th century, chemists working in the pharmaceutical industry were developing easy-to-synthesize drugs such as ibuprofen, while vaccinologists were a strange species. They brewed strange mixtures based on wild premonitions.

The basic idea of ​​vaccination is to allow the body to accept the simulation of wild pathogens. Our immune system will learn to recognize this pathogen, but this is not dangerous in itself. Measles and mumps vaccines are grown in eggs; some influenza vaccines are made by cultivating the virus at low temperatures; the first hepatitis B vaccine is given to injecting drug users and gay men with the disease The blood is purified and disinfected.

But the hepatitis vaccine Heptavax-B introduced in the 1980s was actually a big step forward, because what it delivered to the human body was only a part of the virus, a viral protein. This more targeted approach eliminates many of the risks and disadvantages of providing people with a complete virus, even a virus that has been weakened, split in half, or otherwise destroyed. It also has the benefit of stimulating the body to produce more antibodies that can neutralize the real virus and reduce the immune system fires that can cause dangerous reactions.

A few years after the introduction of Heptavax-B, the key protein will no longer be isolated from human blood, but will be manufactured in genetically engineered yeast-this is the scientific first of vaccines. In fact, it was the advances in gene sequencing and splicing technology in the 1970s and 1980s that finally brought vaccinology into the modern era. This revolution is part of the safe development of a Covid-19 vaccine by scientists in record time. The mRNA and adenovirus vector vaccines currently approved in the United States contain genetic instructions to make coronavirus spike proteins.

This brings us to the last weird innovation, which allows those genetic instructions, at least when they are in the form of mRNA, to sneak into our cell membranes. Hungarian biochemist Katalin Karikó is considered a key innovation in mRNA, and she started her scientific career behind the iron curtain when reagents were scarce. She once had to extract a key ingredient from cow brain in a step-by-step formula from the 1950s to create tiny fat bubbles called liposomes, which can push drugs through cell membranes.

Scientists dream of doing the same thing with RNA, but the molecule has a negative charge, and lipids cannot have a permanent positive charge, otherwise the cell membrane will be destroyed. In the late 1990s and early 2000s, they began to look for tricks to induce RNA and lipids to combine to form tiny solid spheres called lipid nanoparticles. Moderna and Pfizer's vaccines rely on lipid nanoparticles.

We have certainly come a long way since the time of Benjamin Jesty. Unlike ivermectin, hydroxychloroquine, or any unproven treatment touted on Facebook by your uncle, the Covid-19 vaccine is now likely to prevent millions of people from being hospitalized or dying. They represent the culmination of decades of research, and scientists know how and why they are more effective than many widely used drugs. There is no reason to continue living in the dark ages. You can get vaccinated.

Brendan Borrell is a biologist and journalist. He has written articles on science and the environment for dozens of media, including Outside, Bloomberg Businessweek, Nature, The New York Times, Scientific American "And Smithsonian Institution. He lives in Los Angeles, and "The First Shot" is his first book.

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