Kawaoka was able to create a hybrid flu virus that is transmitted via respiratory droplets, meaning it can spread through the fluid a person (or in this case, a ferret) sneezes out or coughs up. [10 Deadly Diseases That Hopped Across Species]
Two key factors made the virus transmissable. One involved a protein called haemagglutinin, or HA, which is what gives H5N1 its name; the number 5 says what type of haemagglutinin it is. The other involved combining the genes from the H5N1 virus with that of another called H1N1, or swine flu, which caused a pandemic in 2009 in Asia.
The HA protein only connects to a molecule called alpha 2,3 linked sialic acid. Birds carry that receptor in their respiratory and digestive tracts. Humans and other mammals also have it, but it is deeper in the lungs and harder for the virus to reach. Flu viruses like H1N1 that infect humans link to a receptor called alpha 2,6 linked sialic acid, which resides in mammals' respiratory systems.
So the first thing was to change the HA protein into something that would bind to the molecules in a mammalian respiratory tract. To do that, Kawaoka and his team introduced random changes in the "head" of the HA molecule, and looked for ones that would bind to alpha 2,6.