Portrait of Isabelle Clark Macdonald, by William Sawyer, 1852
In 1843, Macdonald met and married his first wife, a cousin named Isabella Clark. The marriage was happy at first, but became Macdonald's greatest source of grief after his bride developed a debilitating, mysterious illness. The disease would ebb and flow for the better part of 13 years, and eventually claim her life. Their first child, John Alexander, died tragically after 13 months. Their second son, Hugh John Macdonald, would go on to become premier of Manitoba.