A lot has been written and is known about the life and music of Ludwig Van Beethoven (1770 – 1827), the German composer and pianist. One of the things that we don’t know or can’t explain is why he became obsessed with an insignificant waltz written by Diabelli, his music publisher. Beethoven spent four years, 1819 to 1823, near the end of his life, when he was not in the best of health, writing (intermittently in fits and starts) what would eventually amount to 33 variations on a simple but unexceptional melody. Today, music scholars consider Beethoven’s “Diabelli Variations” as exceptional. But what prompted the genius to devote so much time to them remains a mystery.

Presumably driven by his own sense of investigative curiosity, playwright Moises Kaufman (“The Laramie Project”), who also serves as director, explains the mystery through a dramatic supposition in which a present day musicologist becomes obsessed with explaining Beethoven’s own obsession with this “insignificant” waltz. “33 Variations” is a fascinating, elegantly written, absorbing play with an interestingly developed leading role. It serves nicely as a compatible vehicle for the very fine actor Jane Fonda, who is returning to the Broadway stage after a 46-year absence.

It’s terrific that we see her stunning and svelte in the first part of the play as her character is obliged to take a turn for the worst. In it, she plays Dr. Katherine Brandt, the American musicologist who is also not in the best of health. Brandt is afflicted with Amyotrophic Lateral Sclerosis (ALS) more commonly known as Lou Gehrig’s Disease; its physically impairing progression parallels quite astutely with Beethoven’s deteriorating health. Brandt also has an impaired relationship with her adult daughter, Clara (Samantha Mathis), who opposes Brandt’s decision to leave the U.S. and venture to Bonn, Germany, and Beethoven’s birthplace. Brandt intends to immerse herself in the mystery behind the genius’ 33 variations.

Kaufman has cleverly devised the play to evolve as a series of ever-evolving dramatic variations on a single theme: the compulsion to probe into the core of a mystery and to expose more than we ever dreamed. Brandt’s life is juxtaposed against Beethoven’s at a point in both their lives when time is of the essence and a resolution is all-consuming. With the help of German archivist Dr. Gertrude Ladenburger (Susan Kellermann), Brandt is increasingly intrigued by clues, letters, and documentation unearthed during her research.

The play gives comparable parity to Brandt’s ongoing conflicts with Clara and to Beethoven’s (Zack Grenier) excuses to Diabelli (Don Amendolia), who doesn’t understand why the lauded but lately unproductive composer can’t comply with his request to complete one simple variation, to be included in a collection of variations contributed by 49 other composers. Amendolia gets mileage out of being in a constant state of confounded resignation. The Beethoven episodes are not only enlivened by the eccentricities of the maestro but also by his loyal and devoted assistant and future biographer Anton Schindler (Eric Steele), who serves amusingly as a peace-keeping go-between for his volatile employer and the impatient publisher. Grenier, who was memorably despicable as Dick Cheney in “Stuff Happens,” is a little difficult to understand, but he makes Beethoven an affably temperamental curmudgeon.

Mathis delivers sparks of disapproval and dismay as Clara, whose malleable careers from set designer to costume designer are as temporary and dispensable in direct contrast to her mother’s focused career. Colin Hanks, who is making his Broadway debut, is ingratiating as Mike Clark, the nurse who romantically pursues Clara. He is also instrumental in instructing Clara on how to care for her mother when the time arrives. The dating scenes between Clara and Mike are quite disarming. Kellermann brings a firmly Teutonic resonance to her important role as the archivist who becomes Brandt’s close friend.

Fonda has no difficulty making us empathetic to her image of a valiant woman intent on validating her theory even if it means a surreal and delightful confrontation with Beethoven himself. The set design by Derek McLane is a marvel of gliding walls, panels, hanging files of musical manuscripts and projections, all of it busily enhanced by designer David Lander’s extraordinary banks of movable lights. Off stage but visible, Diana Walsh, the play’s pianist/ musical director, offers delicious morsels of Beethoven’s variations. A play about perseverance and passion, “33 Variations” is high on the list of best new plays of the year. ***

“33 Variations,” through Sunday, May 24, Eugene O’Neill Theater, 230 West 49th Street. $67.50 to $117. 212-239-6200.

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