What issue is jefferson referring to as a "fire bell in the night?

In this particular quote, Thomas Jefferson is referring to the issue of slavery as a "fire bell in the night." When saying this, Jefferson is trying to express how this will be a constant issue in the US. When Jefferson wrote this letter (1819) Missouri was applying for statehood. They were applying to be a slave state. If they entered as a slave state, it would throw off the balance of free and slave state representation in the US Congress. Essentially, Jefferson was accurately predicting how deciding whether or not slavery will exist in the new territories gained by America during the early 1800's will result in problems.