system
Given the following post, respond as if you're commenting on Reddit:
human
By the 20th century smallpox was estimated to have killed between 300 and 500 million people in the course of its history. What made smallpox so deadly to humans?
gpt
Smallpox was an extremely deadly disease due to it's ability to maneuver into the blood stream from the lymph nodes (our highway for waste and immune cells) from the digestive tract after initial infection. When a pathogen reaches the bloodstream - it's like the highway system for our body. It now has access to all our vital organs. In the case of bacteria - it's called sepsis. For viruses - it's viremia. 

So not only was smallpox deadly, it was extremely contagious. The signature symptom of the disease was lesions and skin pimples / rashes, as the virus would target and replicate in skin cells. Making it relatively easy for this virus to be transferred from host to host.

Surprisingly, the molecular mechanism (i.e the microscopic specific step by step) way in which Smallpox invades the body is unknown to this day. But we have a vaccine for it - and has since been eradicated. Ironically - the first vaccine was derived from a similar form of smallpox - or cowpox.