Van Leeuwenhoek was the first to observe microorganisms using self-made microscopes in the 1670s. Throughout the 17th-18th centuries, scientists debated whether microorganisms arose spontaneously or from other organisms. Redi provided evidence against spontaneous generation by showing that flies lay eggs on meat. Spallanzani strengthened this by showing microbes did not grow in sterilized broth. Pasteur disproved spontaneous generation through experiments isolating microbes from air. Koch and others established the germ theory of disease in the late 1800s, showing specific microbes cause specific illnesses. Jenner developed the smallpox vaccine in 1796, providing the first example of disease prevention through inoculation