1. Beat the Elite Four and become the Champion: This is the first requirement. You need to complete the main story of the game and defeat the Elite Four.
2. Talk to Professor Oak: After becoming the Champion, return to Pallet Town and speak to Professor Oak. He'll tell you about a new challenge: catching the legendary Pokémon, Mewtwo, which resides on New Island.
3. Head to the Kanto Safari Zone: Travel back to the Kanto region. You'll find the Safari Zone in Fuchsia City.
4. Enter the Safari Zone: You'll have to pay a fee to enter the Safari Zone, just like you did before.
5. Catch the legendary bird: Inside the Safari Zone, you'll need to catch the legendary bird that was missing from your region. This will depend on which version of the game you're playing:
* HeartGold: Catch Articuno.
* SoulSilver: Catch Zapdos.
6. Travel to Cinnabar Island: After catching the legendary bird, head to Cinnabar Island.
7. Enter the Seafoam Islands: The Seafoam Islands are located on the western side of Cinnabar Island.
8. Follow the path: Inside the Seafoam Islands, follow the path that leads to the bottom.
9. Enter Route 22: At the end of the path in the Seafoam Islands, you'll find a passage leading to Route 22.
Note: Route 22 is mainly a connecting route that leads to the legendary Pokémon, Mewtwo, on New Island.