A little over a year ago when the news broke that a lone gunman had shot Arizona Congresswoman Gabrielle Giffords and 18 bystanders at a meet-and-greet in a grocery store parking lot, friends and colleagues turned to me, mixing accusation and pity, and asked: "Nietzsche?" I wasn't surprised by the immediate assumption that Jared Lee Loughner, the 22-year-old college dropout, who had unleashed his fury in a shower of bullets, must have been a Nietzsche reader and self-fashioned Übermensch. Since I began researching the history of American interest in the German philosopher in the late 1990s, three high-profile rampages by angry, disaffected young men left a bloody trail back to his ideas: the 1997 Pearl High School shootings; the 1999 Columbine High School massacre; and the 2001 brutal double homicide of husband-and-wife Dartmouth College professors in their home.

Expressing the sentiments shared by the other perpetrators, the 16-year-old Pearl High School shooter, Luke Woodham, announced in his manifesto: "I am not insane! I am angry … I am not spoiled or lazy, for murder is not weak and slow-witted, murder is gutsy and daring." Nietzsche did not regard the murder of God gusty and daring, but rather, the terrifically unintended consequence of the zeal for modern knowledge. Nevertheless, Woodham found inspiration in "sec. 125 of the Gay Science 'madmen'" – Nietzsche's famous parable of 1882, where he first introduces the theme of the death of God.

Though the most zealous iconoclasts of all things conventional, these disturbed assailants enacted a ritual that the most famous Nietzsche-intoxicated murderers – University of Chicago students Nathan Leopold and Richard Loeb – had already, in 1924, made conventional. That is, a killing by self-aggrandised young men eager to demonstrate to their parents, teachers, classmates, and themselves, that God is dead, and that they are the Übermenschen to take his place.

The spectacle of an imbalanced, disaffected young man brandishing a Nietzsche text in one hand and a murder weapon in the other may be the clichéd image of the fascination with Nietzsche in America, but it fails to capture an altogether different tendency in American Nietzsche exegesis. Rather than embrace Nietzsche as an atheistic nihilist, many of his 20th-century American readers – religious and agnostic alike – engaged in serious, if agonised, efforts to read his "death of God" as a challenge to a more robust humanism, even a more fulfilling Christianity.

An important early commentator who enlisted Nietzsche not to abandon his faith, but to make it more rigorous intellectually and more demanding spiritually, was the University of Chicago theologian and Baptist minister, George Burman Foster. In his controversial 1906 book The Finality of the Christian Religion, Foster took Nietzsche's attacks on Christianity as a welcome challenge to its claim to be an "authority-religion" – the ultimate arbiter of meaning and truth. Nietzsche helped Foster see that the "conviction of the finality [ie absoluteness] of the Christian religion" could not be reconciled with the insights of modern historicism and naturalism. Foster's Nietzsche spoke not to atheists certain in their unbelief, but rather to spiritual seekers unconvinced by scientific answers to theological questions, unsatisfied by secular forms of enchantment, and yet persuaded that a "God outside the cosmos is dead".

Foster died in 1919, but the determination to wrestle with the implications of a godless universe he exemplified continued to animate American intellectual life throughout the roaring 20s. F Scott Fitzgerald's This Side of Paradise (1920) opened the decade by announcing the arrival of his spiritually and psychically "lost generation" in the aftermath of world war one. But even as expressed by one of its most infamous party boys, this lostness was neither a giddy embrace of indeterminacy nor a weepy retreat into nihilism in a world turned upside-down, but a need for moral reckoning among a generation who had "grown up to find all Gods dead … all faiths in man shaken".

The death of God continued to haunt Nietzsche's American readers unable to find consolation in religious belief but unwilling to deny their religious urges. This sentiment found powerful expression at the decade's end in Nation critic Joseph Wood Krutch's 1929 confession The Modern Temper. Krutch presented a disturbing picture of modern man taunted by the "phantom of certitude" that remained after science had rendered religion an "illusion". "God, instead of disappearing in an instant, has retreated step by step and surrendered gradually his control of the universe," leaving moderns feeling psychically and spiritually abandoned. Though dark and uncompromising, Krutch, in the end, refused to assent fully to the vision of a morally and aesthetically gutted universe; he defiantly pledged allegiance (as if to a stirring lost cause) to a precariously human, if, all-too-human, humanism.

In the decades to follow, these efforts to resist the meaninglessness left in God's absence would continue to find powerful spokespeople in American intellectual life. Just as mid-century Nietzsche translator Walter Kaufmann insisted that Nietzsche's pronouncement was "an attempt at a diagnosis of contemporary civilisation, not a metaphysical speculation about ultimate reality", the religious scholars and clergy associated with the "Death of God" theological movement in the 1960s maintained that it helped intellectually honest religious moderns come to terms with their faith in the dramatically altered moral and intellectual landscape, following the terrors of Auschwitz, Hiroshima and Nagasaki. Though Kaufmann later came to criticise what he regarded as the Death of God theologians' effort to employ "God is dead" for religious apologetics, his own insistence that Nietzsche's claim was an imperative for, not an abandonment of, moral inquiry harmonised with theirs.

At century's end, the conservative commentator Allan Bloom surveyed Nietzsche's dominating influence in America in his Closing of the American Mind (1987), and lamented that readers had used the German philosopher's assaults on truth to underwrite their fuzzy-headed "nihilism with a happy ending". This may seem an odd contrast with the image of the menacing, acne-faced Nietzschean Rambo, so dominant in the decades to follow. And yet both portray the American Nietzsche as one unwilling to give up on finalities. Though odd bedfellows, together they have obscured the longstanding practice in American intellectual life to read "God is dead" not as a closing, but rather an opening of minds, hearts and moral accounts. This American Nietzsche was neither a nihilist nor big on endings. This Nietzsche declared that "God is dead" to awaken his readers from their moral slumber, in the hope and promise of renewal.

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