On April 27, 1817, Jane Austen sat down and wrote her will, leaving almost all of her assets—valued at less than 800 pounds sterling—to her sister Cassandra. In May, the sisters moved to Winchester, England, so the bedridden Jane would be near her doctor. On July 18, only a few days after dictating 24 lines of comic verse to Cassandra, Jane died.

Since at least the 1960s Austen scholars, doctors and fans have tried to retrospectively identify the curious illness that killed the 41-year-old English author. Crime novelist Lindsay Ashford thinks she has finally solved the mystery. Austen, she proposes, died of arsenic poisoning. And scientists have the tools to find out if she is right.

Ashford came to this conclusion after living in Austen's village of Chawton, England, where she had been researching a new book. While reading Austen's letters, Ashford noticed a particularly telling passage in a letter to Austen's niece Fanny Knight in March 1817: "I have had a good deal of fever at times and indifferent nights, but am considerably better now and recovering my looks a little, which have been bad enough, black and white and every wrong color."

Thanks to a background in forensics and years of research for her own novels, Ashford knew that one of the symptoms of arsenic poisoning is hyperpigmentation, or "raindrop pigmentation," in which the skin turns into a patchwork of dark and light areas with unusually high or low levels of melanin. Chronic arsenic poisoning, in fact, can warp and mottle the skin in all kinds of ways, and even cause skin cancers.

In Austen's time, as Ashford also knew, many medications included arsenic. Potassium arsenite was the main ingredient in the immensely popular Fowler's Solution, which was prescribed for diseases like syphilis and for more minor ailments like the joint pain of which Austen complained in her final letters. Ashford thinks Austen was unintentionally poisoned by arsenic-based medication.

Unlike all the other theories about Austen's death, the arsenic hypothesis can be easily confirmed or refuted by science. All that's needed is a little piece of Jane Austen herself—say, a piece of her hair. After Jane died, Cassandra cut off much of her sister's hair and distributed the locks among relatives and friends, as was customary. One lock found its way to Austen collectors Alberta and Henry Burke, who, for reasons that remain unclear, reportedly had the hair tested for arsenic. The results came back positive. Perhaps the couple, like Ashford, suspected that arsenic killed Austen and wanted evidence. Later, the Burkes donated the hair to the Jane Austen House Museum in Chawton, where it remains to this day.

Scholars had largely overlooked the Burke test, but Ashford heard about it from Elsa Solender, former president of the Jane Austen Society of North America. Ashford asked librarians at Goucher College in Baltimore, which holds the Burkes's vast Jane Austen collection, to search for records of the arsenic test. They found none.

Louise West, curator of the Jane Austen House Museum, says she and the trustees are aware of Lindsay Ashford's hypothesis, but have not yet reached any decisions about testing the Austen's hair for arsenic. If they decide to proceed, the analysis should not be too difficult to arrange.

Scientists have at least three sophisticated techniques that could detect arsenic in Austen's hair, two of which would not damage her faded follicles. The most sensitive test is probably neutron activation analysis, says analytical chemist Brian Jackson of Dartmouth College. In this technique, a few milligrams of hair are bombarded with neutrons, forcing stable elements in the hair to radioactively decay and emit gamma rays, which are unique to each chemical element in the follicles. One study notes that a single strand of human hair 12 centimeters long weighs on average 0.62 milligram, so neutron activation might require only five or fewer strands. However, only a few facilities around the world have a neutron bombarder. Oak Ridge National Laboratory in Tennessee is one: It houses the Spallation Neutron Source and High Flux Isotope Reactor.

An alternative is bulk x-ray fluorescence, which would also require around five strands of hair. Scientists subject the hair to high energy x-rays that excite the atoms within, which in turn emit their own x-rays. The frequencies of these secondary x-rays are unique to atoms of different elements, thereby revealing the hair's chemical composition. A variation of the technique, x-ray microprobe fluorescence, requires only a strand or two of hair if researchers have access to an incredibly powerful light source, such as the National Synchrotron Light Source at Brookhaven National Laboratory in Upton, N.Y., or the Diamond Light Source in the U.K.

As a last resort, scientists could try inductively coupled plasma mass spectrometry. Austen's follicles would be dissolved in acid and sprayed into a mass spectrometer—an instrument that atomizes the solution with an intensely hot flame before filtering the atoms for those belonging to a particular element, like arsenic. Jackson estimates that mass spectrometry requires about 10 milligrams of hair—between 10 and 20 strands.

Finding extremely high levels of arsenic in Austen's hair—above three parts per million—would strongly indicate poisoning as the primary cause of the novelist's death. Typical levels of arsenic in human hair do not exceed 0.5 to one ppm.

It is also possible that Austen's earliest symptoms were linked to a different illness and, only when doctors tried to treat it, was she poisoned by arsenic-laced medications. The most popular retrospective diagnosis of Austen's fatal malady is Addison's disease, a rare disorder in which the adrenal glands, walnut-size hormone factories that sit atop the kidneys, begin to malfunction. Symptoms include severe vomiting, fatigue and—as with arsenic poisoning—skin discoloration. These symptoms also match those Austen described in the letters she wrote during the year before her death, which mention "bilious attacks"—her joking name for nausea and vomiting—as well as fever, exhaustion and joint pain.

Noninvasive testing of Austen's hair could provide the clearest answer yet to a long-standing mystery. And it would certainly be less uncouth than unearthing the esteemed novelist's bones—an idea some people have earnestly suggested. Austen, whose novels poke fun at fastidious characters that obsess over appearances and exaggerate illness when convenient, would probably find all the fuss over her hair a little disturbing, but also rather comical.