Stored away in the rare-book library at Yale University is a late-medieval manuscript written in a cramped but punctilious script and illustrated with lively line drawings that have been painted over, at times crudely, with washes of color. These illustrations range from the fanciful (legions of heavy-headed flowers that bear no relation to any earthly variety) to the bizarre (naked and possibly pregnant women, frolicking in what look like amusement-park waterslides from the fifteenth century). With their distended bellies, stick-like arms and legs, and earnest expressions, the naked figures have a whimsical quality, though their anatomy is frankly rendered—something unusual for the period. The manuscript’s botanical drawings are no less strange: the plants appear to be chimerical, combining incompatible parts from different species, even different kingdoms. (Click on the images to expand.) Tentacled balls of roots take the forms of animals, or of human organs—in one case, sprouting two disembodied heads with vexed expressions. But perhaps the oddest thing about this book is that no one has ever read it.

That’s because the book—called the Voynich manuscript after the rare-book dealer who stumbled upon it a century ago—is written in an unknown script, with an alphabet that appears nowhere other than in its pages. The writing system is oddly beautiful, full of looping and fluid curves. A series of distinctive letters, called “gallows” for their resemblance to a hangman’s scaffold, are sometimes conjoined with other letters, or have been embellished with elaborate curlicues by a scribe. What these glyphs signify—whether they represent phonetic information or numeric values or something else—is anyone’s guess. Judging by its illustrations, the manuscript seems to be a compendium of knowledge related to the natural world, including a section about herbs, a section apparently detailing biological processes, various zodiac charts, and pages devoted to the movements of celestial bodies, such as the transit of the moon across the Pleiades. The writing flows smoothly hesitation from one letter to the next; based on the handwriting, it’s thought to be the work of at least two and as many as eight practiced scribes, and possibly required years of labor.

I first learned of the Voynich in 2010. I was completing an M.F.A. in fiction at the University of Virginia, and, anticipating dismal job prospects, had decided to try my hand at a Dan Brown–style thriller. It was to be about “Book M,” a likely apocryphal Rosicrucian encyclopedia of arcane wisdom written, in the early fifteenth century, in “magical language and letters” by Christian Rosenkreuz and the seven other founders of the order. The protagonist of the novel discovers that the Voynich, which dates from the same time, is in fact the long-vanished “Book M,” whose secrets will, if discovered … well, you know the plot. I spent a sweltering summer in Virginia trying to learn how to write a pulpy thriller (it’s a lot harder than it looks) while devoting more and more of my time to researching the Voynich. I made an electronic facsimile of the book for my iPad using high-resolution scans of the pages, and spent hours—which turned into days and weeks—flipping through the pages, captivated by the smallest details in the margins. A tiny drawing of a corpse holding its stomach next to discarded morsels of food, on the recto of Folio 66, sent me rushing to the university library to look up poisonous plants, which led me to research medieval pharmacopeias, which led to trade routes between Europe and India crossed by Arab merchants.

By the end of the summer, my novel was no nearer to completion. But a breakthrough on deciphering the Voynich seemed closer than ever.

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I wasn’t the only one who believed that he could crack the book’s secrets. The first person said to have owned the manuscript was the Holy Roman Emperor Rudolf II, who reportedly was intrigued enough to buy it from its previous owner for six hundred ducats, around ninety thousand dollars in today’s money. (According to the manuscript’s radiocarbon dating, the book was already nearly two centuries old at the time of his purchase.) Rudolf was a devotee of the unusual—he collected dwarfs and stocked an entire regiment in his army with “giants”—and his fixation on alchemy and the occult made Prague under his rule a center for both mystical and proto-scientific inquiry. One prominent figure in Rudolf’s court was Jacobus Horcicky de Tepenec, the imperial pharmacist, keeper of the royal gardens, and the next owner of the Voynich manuscript. Tepenec had reportedly earned the emperor’s favor by curing him of some grave disease. An elixir he manufactured and sold was so in demand that he became the Renaissance equivalent of a snake-oil baron, rich enough that even the emperor turned to him for loans.

Nearly everything about the Voynich manuscript has been contested over the years, and its past ownership is no exception. But a decade ago, the indefatigable Voynich expert René Zandbergen (on whose research I’ve drawn heavily here) was browsing a set of archives from the seventeenth century when he stumbled across a letter that identified the manuscript’s next owner: Georg Baresch, an alchemist in Prague in the first half of the seventeenth century, who had spent twenty years attempting to decipher the script. Despairing of a solution, the alchemist had sent a few sample pages to the cryptanalytic celebrity of the day, a Jesuit polymath in Rome named Athanasius Kircher, who famously—and incorrectly, as it turned out—claimed to have decoded the hieroglyphics of ancient Egypt. The manuscript intrigued Kircher, and he tried to convince Baresch to part with it. Baresch refused. Instead, it fell to Baresch’s friend Marci, who inherited the manuscript when Baresch died, to pass on the rest of the manuscript to the Jesuit scholar. Marci was himself a well-known scientist, and served as physician to the Holy Roman Emperor, despite having once been branded a heretic for speculations on the science of conception and development of the human embryo. In the letter accompanying the Voynich manuscript, Marci describes his late friend’s obsession with cracking the script: “To its deciphering he devoted unflagging toil, as is apparent from attempts of his which I send you herewith, and he relinquished hope only with his life.”

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Whether the Jesuit scholar made any progress with the manuscript is unknown; after the book made it to Rome, it was hidden in Jesuit holdings for nearly three centuries. During the Church’s suppression of the Jesuits, the manuscript was likely transferred to the personal library of the head of the order, Peter Beckx, to shield it from papal confiscation. At any rate, Beckx’s ex libris adorned the book when Voynich bought it, in 1912.

Much can be written about Wilfrid Voynich. An ethnic Pole from the Russian Empire, Voynich was imprisoned in Siberia for revolutionary activities. He escaped, via Manchuria and China, to London, where he met his future wife, Ethel Boole. Boole, the daughter of the famous mathematician George Boole, who became a popular novelist, was enmeshed in Russian revolutionary activity in London; the bookshop that Voynich set up with her was rumored to be a secret front for organization against the tsarist regime. Whatever the reasons for his entrée into the rare-book business, he apparently took to this work and excelled at it. On a buying trip to a place that, in a 1921 lecture on the manuscript, Voynich described vaguely as “an ancient castle in southern Europe” (later identified as the Villa Madragone outside of Rome), Voynich stumbled upon the “cipher manuscript,” and immediately recognized the book’s significance. Based on Marci’s letter found with the manuscript, Voynich became convinced the book was the work of the brilliant thirteenth-century Franciscan friar and Englishman Roger Bacon. And, with the belief that proving Bacon’s ownership would fetch a high price for the work at auction, Voynich enlisted William Newbold, a professor of philosophy at the University of Pennsylvania and a cryptography enthusiast, to attempt to decipher it.