1850, Seacole's half-brother Edward moved to Cruces, Panama, then part of New Granada. There, approximately 45 miles (72 km) up the Chagres River from the coast, he followed the family trade by establishing the Independent Hotel to accommodate the many travellers between the east coast and west coasts of the United States. The number of travellers had increased due to the 1849 California Gold Rush. Cruces was the limit of navigability of the Chagres River during the rainy season, from June to December. Travellers would ride on donkeys approximately 20 miles (32 km) along the Las Cruces trail from Panama City on the Pacific Ocean coast to Cruces, and then 45 miles (72 km) downriver to the Atlantic Ocean at Chagres (or vice versa). In the dry season, the river subsided, and travellers would switch from land to the river a few miles further downstream, at Gorgona. Most of these settlements have now been submerged by Gatun Lake, formed as part of the Panama Canal.
In 1851 Seacole travelled to Cruces to visit her brother, but shortly after her arrival the town was struck by cholera, a disease which had reached Panama in 1849. Seacole was on hand to treat the first victim, who survived, establishing Seacole's reputation and bringing her a succession of patients as the infection spread. The rich paid, but she treated the poor for free.[3