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This is: The 300-year journey to the covid vaccine, published by jasoncrawford on the LessWrong.
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A covid vaccine has demonstrated 90% efficacy and no significant safety concerns in preliminary data from Phase 3 trials, according to an announcement today from Pfizer and BioNTech SE. The trials aren’t yet complete and the data hasn’t yet been released for independent verification, but this is very good news. (More from STAT News.)
Pfizer/BioNTech’s vaccine, like Moderna’s, is based on “mRNA” technology. If approved by the FDA, it will be the first such vaccine to reach that milestone. From a long-term progress perspective, this is a big deal.
Immunization technology has existed since the early 1700s (and the folk practices it originated in go back centuries further.) We can see the whole 300-year history of the technology as a quest to achieve immunity with ever-more safety and ever-fewer side effects. More recently, it has also become important to be able to react quickly to new epidemics, such as covid.
Here’s how immunization has advanced in stages:
Inoculation
All immunization is based on the observation that exposure to a disease often grants immunity (temporary if not permanent) to subsequent exposure. Long before we knew anything about antibodies or T-cells, people had noticed this simple correlation. Many people got smallpox in the past, but almost no one got it twice. The goal of immunization technology is to achieve that same immunity, but without having to suffer the disease or to risk death or other side effects.
The earliest form of immunization, then, was not a vaccine, but a method in which the patient was given the actual disease itself, in a manner that would cause a mild rather than a severe case of the illness. This was done with smallpox, and the technique was called inoculation or variolation.
This worked with smallpox for two reasons. One, infectious material was easy to obtain, from the pustules caused by the disease itself. Second, contracting the disease through a scratch on the skin caused a much more mild form than contracting it more naturally through inhalation.
Inoculation saved many people from smallpox. But there were downsides. First, the patient still had to contract the disease, causing mild symptoms. Second, there was still a small risk of a severe case; even the best inoculation methods had about a 0.2% death rate. Third, the patient was still contagious while going through the illness, and anyone who caught the disease naturally from an inoculated patient would get the full, severe version. Inoculation thus risked outbreaks.
Vaccination
These problems were solved by the next stage: vaccination. It was observed that cowpox infection granted some form of cross-immunity to smallpox. Thus, the inoculation procedure could be performed using cowpox material, rather than smallpox. Cowpox was a milder and non-lethal disease. This reduced the symptoms and the risk of death, and eliminated the risk of smallpox outbreaks as a result of immunization. This new technique, invented by Edward Jenner in 1796, was called vaccination (from vacca, the Latin word for cow).
So far, however, the technique only worked for smallpox—not for tuberculosis, malaria, influenza, cholera, or any of the other major diseases that caused something like half of all deaths in that era.
Engineered vaccines
The next stage would wait almost ninety years. Louis Pasteur, a pioneer of microbiology who along with Robert Koch established the germ theory, was the first to discover how to create vaccines for any disease other than smallpox.
Cowpox can be seen as a “natural vaccine” against smallpox: a natural virus that grants smallpox immunity but produces milder side effects. Pasteur’s accomplishment was to create artificial, engineered vaccines.
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