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Calvin Ellis Stowe was working on a book called Origin and History of the Books of the Bible, and in 1868 it was published to great acclaim. It was a bestseller, and the royalty checks further padded the Stowes' bank account. Harriet founded a school for emancipated slaves and began teaching again.

In 1869, a book was published that drove Harriet to make an ill-fated decision. Lord Byron's last mistress, Countess Guicciolo, had written a book about her life with Byron and in the book disparaged Lady Byron. Harriet was upset, and she decided to reveal that Lady Byron's husband was incestuously involved with his half-sister. Everyone in Harriet's inner circle begged her not to do so, saying there would be severe consequence if she did–her reputation, including the prestige in which her literary career had accrued, would be damaged by such a revelation. Harriet ignored these warnings.

"The True Story of Lady Byron's Life" was published in the August 1869 issue of The Atlantic Monthly. The issue sold out of newsstands at once and created great controversy. As her family predicted, her supporters were few. Most found her actions reprehensible and even laughable. Her detractors attacked the veracity of Harriet's story, pointing out that she offered no proof whatsoever to the charge of incest, and relied solely on Lady Byron's memory. Harriet suggested that both she and the late Lady Byron were not believed because they were women.

For the first time in her life, Harriet Beecher Stowe found herself the object of almost unanimous derision, and was mocked in newspaper editorials and satirical articles as a meddler and a hack writer. She was bewildered at the outcry and the appearance of books defending Byron prompted her to write her own book, which she titled Lady Byron Vindicated. It appeared in 1870. It offered no new proof for her charges and attacked Byron's poetry. It was widely dismissed.

The same year that the Byron controversy turned Harriet Beecher Stowe's life upside down, an even more tragic event darkened her household. Her embattled son Frederick, whose long struggle with alcoholism had tormented his family, took passage on a ship from San Francisco to the Far East. Somewhere along the way he disappeared and was never found again. Harriet and Calvin were heartbroken at having lost a third son.

In 1873, Harriet and Calvin moved out of the mansion they'd bought years before and moved into a more modest home in Hartford. Their new neighbor was a young writer named Mark Twain. He was a frequent visitor to the Stowe house and amused Harriet with his jokes and witticisms. That same year, Harriet published a book of travel writings about Florida called Palmetto Leaves. If anyone doubted if the public would buy her books after the unfortunate Byron affair, those doubts were eradicated by the appearance of Palmetto Leaves: it was an instant bestseller, and it turned Florida into a popular wintering spot almost immediately.

Harriet produced prodigious amounts of new writing each year. My Wife and I was published in 1871 along with Pink and White Tyranny.Women in Sacred History was published in 1873. Two children's books, Little Pussy Willow and Betty's Bright Idea, appeared in 1870 and 1876, respectively. The novel We and Our Neighbors appeared in 1875. In 1872, Harriet embarked on a lecture tour. The shyness that kept her from public speaking during her first trip abroad was gone, and now she took the lectern happily. All of her engagements were sold out.

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