The Isenheim Altarpiece is an altarpiece sculpted and painted by, respectively, the Germans Niclaus of Haguenau and Matthias Grünewald in 1512–1516. It is on display at the Unterlinden Museum at Colmar, Alsace, in France. The museum celebrated the 500th anniversary of the work in 2012. It is Grünewald's largest work, and is regarded as his masterpiece. It was painted for the Monastery of St. Anthony in Isenheim near Colmar, which specialized in hospital work. The Antonine monks of the monastery were noted for their care of plague sufferers as well as their treatment of skin diseases, such as ergotism. The image of the crucified Christ is pitted with plague-type sores, showing patients that Jesus understood and shared their afflictions.

The altarpiece has two sets of wings, displaying three configurations:

Wings closed:

With the exception of certain holy days, the wings of the altarpiece were kept closed, displaying The Crucifixion framed on the left by the martyrdom of Saint Sebastian pierced by arrows, and on the right by Saint Anthony the Great, remaining placid although he is being taunted by a frightening monster. The two saints protect and heal the sick, Saint Anthony as the patron saint of the victims of Saint Anthony's fire and Saint Sebastian, whose aid was invoked to ward off the plague. Grünewald's Crucifixion stands as one of the most poignant representations of this scene in Western art due to the artist's masterful depiction of horrific agony, with Christ's emaciated body writhing under the pain of the nails driven through his hands and feet. This body covered with sores and riddled with thorns must have terrified the sick, but also left no doubt about Christ's suffering, thus comforting them in their communion with the Saviour, whose pain they shared. "Grünewald depicts Jesus' body ravaged by crucifixion yet evokes pointedly the Christian message of Jesus' horrible suffering; originally intended for a hospital, the altar painting may have been designed to provide comfort and solace to the sick." Mary, the mother of Jesus, is shown at Christ's right, collapsing in anguish in the arms of John, the beloved disciple of Christ, and shrouded in a large piece of white cloth.

At Christ's left, John the Baptist is accompanied by a lamb, symbolising the sacrifice of Jesus. The presence of John the Baptist is anachronistic. Beheaded by order of Herod in 29 AD, he could not possibly have witnessed the death of Christ. This last figure announces the New Testament by crying out in Latin, illum oportet crescere me autem minui (Vulgate, John 3:30), "He must increase, but I must decrease." The inclusion of John the Baptist in this scene is symbolic, since he is considered as the last of the prophets to announce the coming of the Messiah.

Outer wings opened:

The outer wings of the Isenheim Altarpiece were opened for important festivals of the liturgical year, particularly those in honour of the Virgin Mary. Thus are revealed four scenes: the left wing represents the Annunciation during which the archangel Gabriel comes to announce to Mary that she will give birth to Jesus, the son of God. The Virgin Mary is depicted in a chapel to indicate the sacred character of the event. In the central corpus, the Concert of Angels and the Nativity are not independent scenes but instead fit within a unified concept: the viewer witnesses Christ's coming to earth as a newborn baby, who will be led to combat the forces of evil personified by certain of the angels, disturbing in their physical appearance. A number of symbols provide keys to aid in interpretation: the enclosed garden represents Mary's womb and is a sign of her perpetual virginity, the rose bush without thorns refers to her as free of original sin, the fig tree symbolises mother's milk. The bed, the bucket and the chamber pot underscore the human nature of Christ. Lastly, the right wing shows the Resurrection, in which Christ emerges from the tomb and ascends into Heaven bathed in light transfiguring the countenance of the Crucified into the face of God. The Resurrection and the Ascension are therefore encapsulated in a single image.

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