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In 1846 Greenleaf became a professor of law at Harvard Law School and is perhaps most well-known for his Treatise on the Law of Evidence (3 vols., 1842–1853), a classic of American jurisprudence. Greenleaf is also recognized as an important figure in the development of Christian apologetics via his application of rules of evidence and cross-examination in his book Testimony of the Evangelists to establish the authenticity of the gospel accounts in the New Testament.

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