The history of smallpox eradication: You should know

As one of the viruses that has completely disappeared from the world, understanding the history of smallpox's extinction can help us think about where we humans should go in the face of unknown viruses as the new coronavirus rages today.

Smallpox is called smallpox because those who survived the infection would have scars due to the rash all over their body. The smallpox virus is one of the oldest and most lethal viruses. How old is it? Since human records began, the fight against smallpox has lasted for 3,000 years. The mummy of the Egyptian pharaoh Ramses V, who died in 1156 AD in ancient Egypt, showed signs of suspected smallpox rashes. Smallpox originated in ancient Egypt and later spread to Europe and Western Asia through wars and trade among Eurasian countries. Roman Emperor Aurelius, Queen Mary II of England, German Emperor Joseph I, French Emperor Louis XV, and Russian Tsar Peter II all died at the hands of smallpox.

Not only abroad, but also in my country's history, the 17th to 18th centuries were the most rampant period of smallpox. Four of the 12 emperors of the Qing Dynasty were infected with smallpox, and Shunzhi and Tongzhi were directly killed by this disease. On the seventh day of the first lunar month in 1661, the 24-year-old Emperor Shunzhi died in the forbidden palace. The "Records of Emperor Shizu of the Qing Dynasty" only used 11 words to describe it: "Dingsi, night, Zi Ke, the emperor died in the Yangxin Palace." The emperor's untimely death is easy to arouse various associations and speculations, and the vague description in the official history just gave all kinds of rumors an opportunity to spread. Although there are many different opinions, the real cause of Shunzhi's death can still be traced. According to the notes of Zhang Chen, the secretary of the Qing court, because Emperor Shunzhi was seriously ill, the court pardoned the prison to pray for good luck, and also issued an order not to fry beans and light lamps. Smallpox was called "pox" at the time, and it was a unique taboo not to fry beans and light lamps when there were patients. Of course, this is a homophonic culture that only exists in China. According to the autobiography written by Wang Xi, the then Minister of Rites, when Emperor Shunzhi urgently summoned him, he said in person, "I have smallpox and will soon die." These two confirm each other, which deepens the credibility of Shunzhi's death from smallpox. In addition, the body of Emperor Shunzhi was cremated. Not only was the body burned, but also the things he used were burned together, which indirectly supports the claim that he died of smallpox. In the issue of the selection of heirs, in principle: if there is a legitimate son, the legitimate son shall be established, and if there is no legitimate son, the eldest son shall be established. But in fact, when Shunzhi had no legitimate son, the third son Xuanye, who was later Emperor Kangxi, was chosen. One reason that cannot be ignored is that he had smallpox.

What is smallpox, which is so rampant that people turn pale at the mention of it? Smallpox is caused by infection with the variola virus, which includes the variola major virus and the variola minor virus. Smallpox caused by infection with the variola major virus is more serious, with a mortality rate of up to 30%, while smallpox caused by infection with the variola minor virus is called smallpox/sub-variola, with a lower mortality rate of about 1%. Humans are the only host of the smallpox virus, and smallpox patients are the source of infection. They are contagious from infection with the virus to scabs, and are most contagious during the rash. Smallpox has become the only infectious disease that humans have completely eradicated so far. This is not only due to human wisdom, but also because smallpox only infects humans and is only transmitted between people. The smallpox virus is very stable and can survive in scabs for several years. Under natural conditions, the smallpox virus remains pathogenic for several weeks. There are two ways of transmission of smallpox, respiratory transmission and contact transmission. Smallpox can be transmitted through droplets produced by the patient's breathing, coughing, sneezing, etc., and can be transmitted through the air if you are in a small, closed space with the patient. Smallpox can also be transmitted through contact with the patient's skin lesions (such as scabs, blister fluid, etc.), and even through contact with the patient's clothing, bedding, etc. The incubation period of smallpox is 10 to 14 days or even 7 to 19 days. After the patient is infected with the smallpox virus, the virus first multiplies in the respiratory tract and then migrates to the regional lymph nodes. Primary viremia is asymptomatic. After 3 to 4 days after infection, the virus can further migrate to the spleen, bone marrow and distal lymph nodes. Secondary viremia occurs 7 to 11 days after infection, followed by fever, headache, back pain and extreme fatigue, and then maculopapular rash appears, gradually turning into blisters and pustules, and then the pustules scab, leaving scars after the scabs fall off. At the beginning, both at home and abroad, there was nothing they could do about the outbreak of smallpox. The only thing they could do was to isolate the patients with the disease and burn everything they had touched after death.

Even when smallpox was rampant, the wise Chinese did not give up resistance. As the number of cases of smallpox infection increased, people accidentally discovered the characteristics of smallpox - as long as people who had smallpox and survived would never get it again in their lifetime. The Kangxi mentioned earlier is a good example. So ancient Chinese doctors began to try to let patients infected with smallpox but not seriously ill come into contact with healthy people, so that the smallpox virus could spread in a small range. This practice has achieved certain results, and most people can survive. This has become one of the earliest simple attempts in immunology in China. At the turn of the Ming and Qing Dynasties, a safer "human pox vaccine method" appeared. That is, the pox on the skin of smallpox patients with mild symptoms was removed, dried and ground into powder, and then people who had not had smallpox were allowed to inhale it into the nasal cavity, which is equivalent to the inactivated preparation in modern immunology. This vaccine method has a very low mortality rate. In the 21st year of Kangxi in the Qing Dynasty, that is, in 1682 AD, under the leadership of the Qing government, large-scale vaccinations were carried out nationwide, greatly reducing the risk of smallpox outbreaks in the Qing Dynasty. Although the "smallpox method" was effective, it also had a flaw, which was that the toxicity was difficult to control. Some people would die from smallpox caused by the vaccination, or experience some adverse reactions, making it difficult to guarantee absolute safety.

In the middle of the 18th century, Edward Jenner, a British country doctor, overheard someone talking about how milkmaids on the ranch would never get smallpox because they had had cowpox. Based on this discovery, he researched and published several papers on the cowpox vaccine, showing that the cowpox vaccine was much safer than the human pox vaccine, and it almost never caused pox, let alone was not fatal. Since then, the cowpox vaccine has replaced the human pox vaccine and has become the first choice for preventing the smallpox virus, and has been widely popularized in European countries and their colonies. In 1805, Alexander Pearson, a ship doctor of the East India Company, brought the cowpox inoculation technique to Guangzhou, and China's history of fighting smallpox entered a new era.

In the early days of the founding of the People's Republic of China, smallpox was still one of the acute infectious diseases with the highest mortality rate in my country. On February 6, 1952, the Ministry of Health issued a vaccination instruction, planning to vaccinate 260 million people that year. This was the first time in human history that an organized vaccination campaign was carried out for such a large population. Under strict organization and the hard work of medical staff in New China, China's cowpox vaccination rate reached more than 90%, and by 1954, there was no smallpox epidemic in large and medium-sized cities across the country. In 1959, the last smallpox outbreak in my country was extinguished in Cangyuan County, Yunnan Province, and the smallpox virus gradually faded out of the Chinese people's vision. In June 1961, the World Health Organization confirmed that my country had eliminated smallpox since then. The phenomenon of smallpox ravaging and claiming the lives of countless Chinese people has gradually become history. In 1966, the World Health Organization proposed that countries strengthen cooperation, increase vaccination density, and eradicate the global smallpox epidemic. At that time, there was no smallpox in developed countries, and only underdeveloped countries in Asia, Africa and Latin America still had smallpox. By 1980, smallpox was basically extinct in the world. Today, October 25th of each year is designated as the day of human smallpox extinction. Now, there are only two places in the world where smallpox bacteria are preserved, one is the Victor Laboratory in Russia, and the other is the Centers for Disease Control in Atlanta, USA. The purpose of preserving is to study the origin of the bacteria and its genetic map, and to find new vaccines and anti-viral drugs, because apart from vaccination, there is still no good way to treat smallpox. Yes, that's right, even though smallpox has been extinct, we still haven't found a way to treat smallpox, only prevention. The laws of nature are complex. For various epidemic bacteria like smallpox, humans have never really understood them, let alone defeated them.

Even with the development of medicine, humans still cannot eliminate some infectious diseases. For example, AIDS, tuberculosis, some influenza, yellow fever, dengue fever, Ebola virus, etc. The history of human struggle against viruses and bacteria is that we constantly encounter unknown viruses and bacteria, and constantly struggle against known microorganisms. Facing visible enemies, we can still try to defend ourselves. But facing invisible enemies, we are really helpless. In addition to the factors of bacteria and viruses themselves, we have to mention the increasingly serious ecological problems, such as environmental pollution, climate warming, ecological imbalance, resource depletion, soil erosion, desertification, etc. The Ebola virus outbreak in the village of Meliendo in Guinea in December 2013 may be because the forest was cut down, and the bats had nowhere to live. They fled to the surrounding areas of the village and were preyed on by some children, which triggered an "unprecedented outbreak."

The abuse of antibiotics leads to a decline in human immunity, which is also one of the reasons why infectious diseases cannot be eliminated. Antibiotics once defeated most epidemics, and people became more and more dependent on them. However, pathogens continue to mutate in order to adapt to antibiotic attacks, environmental changes, air pollution and other factors, resulting in an increasingly serious problem of drug resistance.

It is too early to put an end to infectious diseases. After all, there are still many unsolved problems in microbiology and immunology. Perhaps one day, we can effectively prevent the resistance and mutation of pathogens and learn to live in harmony with nature forever. Only then can we seize the initiative in the fight against infectious diseases or run faster than the virus. French novelist Albert Camus once said in "The Plague" that only human integrity can defeat the plague. After careful consideration, it seems to be the case.

References:

[1] Vista World, Issue 485: How did once-prevalent infectious diseases disappear?

[2]Carroll, Dennis, et al. "The global virome project." Science 359.6378 (2018): 872-874.

[3]Zhong, Zhi-Ping, et al. "Glacier ice archives fifteen-thousand-year-old viruses." BioRxiv (2020).

[4] The Great Pandemic: A Century of Global Pandemics, by Mark Honigsbaum, CITIC Publishing Group

[5] Smallpox (baidu.com)