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Jack has written more than 500 articles and essays for The Atlantic, Scientific American Mind, Wired, American Heritage, The History Channel Magazine, The Washington Post Magazine, Minnesota Monthly, and many other publications.

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Entries in laura ranum (1)

Monday
Jul302012

Did Abraham Lincoln Have Ataxia?

Recent research suggests that the U.S. President may have suffered from this mysterious neurological disease. 

For nearly twenty years, people who have a kinship to Abraham Lincoln have been gathering for reunions in Indiana, Iowa, and Kentucky – and medical researchers have been there along with them.The last known photo taken of Abraham Lincoln before his death.

The researchers, led by Laura Ranum, Ph.D., formerly of the University of Minnesota and now with the University of Florida, came not to hear stories of the Great Emancipator or to share potato salad and coffee, but to collect DNA samples and to learn more about the Lincoln family’s medical history. The 299 vials of blood they have carried back to Minnesota contain vital clues to the mystery of spinocerebellar ataxia, a devastating neurological condition that affects about 150,000 Americans. 

What is ataxia?

People with ataxia suffer from a deterioration of the cerebellum, brain stem, and spinal cord ― regions of the nervous system that govern muscle control. Ataxic patients are loosely defined as anyone with clumsiness and a lack of coordination from cerebellar degeneration. 

In many people, a genetic flaw causes the elaborately structured cells of the cerebellum to die off. The disease proceeds gradually, eventually robbing its victims of the ability to walk, hold objects, move their eyes, speak, and perform common activities of daily life. If patients lose control of the muscles for swallowing, they can develop pneumonia or even choke to death.

Unraveling the mystery

 Ranum began her Lincoln family gene hunt in 1992 when she received a phone call from an Ohio physician who described a patient with familial ataxia. When she called the patient, her mother, and several cousins afflicted with the disease, she learned that all were related to President Lincoln. Some even referred to the ataxia in the family as “Lincoln’s disease.” 

When a newspaper reporter in Louisville wrote a story about “Lincoln’s disease,” another offshoot of the family contacted Ranum. This time, the relative was descended from President Lincoln’s aunt Mary. The identification of this second branch of the family means that one of President Lincoln’s paternal grandparents must also have had the disease and passed it on to one or more children. In 1994 Ranum's team mapped the gene to the eleventh chromosome. 

Although the trips to Lincoln family reunions spanned more than a decade, the hardest part of the gene hunt was yet to come. Ranum and her lab colleagues studied the DNA contained in the blood vials collected from Lincoln’s extended family. The search for this gene was particularly difficult because it fell near a region of chromosome 11, called a centromere, that tends to stick together.

Everyone wondered whether the President himself either had ataxia or would have developed it later in life.

In 2005 the group finally found what they had long been seeking: the specific mutation responsible for the Lincoln family’s ataxia. “Any family member with the gene will develop ataxia if they live long enough,” Ranum says. “And their children have a 50 percent chance of getting it, too.” Because both Lincoln’s aunt and uncle on his father’s side carried the ataxia mutation, one of the President’s paternal grandparents had to carry it as well. That means that Lincoln had a 25 percent chance of carrying the mutation himself. 

Eventually the researchers demonstrated that the mutation, an accident of chemistry, affects the function of another protein called a glutamate transporter that normally regulates how much stimulation the brain’s neurons receive. Failure to control this stimulation leads to damaged neurons; in fact, it is what likely causes the death of the cerebellum cells. With the loss of enough of these cells, patients lose control of the movements of their legs, arms, and eyes. 

Inevitably, everyone wondered whether the President himself either had ataxia or would have developed it later in life. Medical historians have long speculated that President Lincoln’s tall stature may have resulted from Marfan syndrome, a disorder of the body’s connective tissue. Ranum says that family history and historical accounts of Lincoln’s gait make it much more likely that the President suffered from ataxia. Finding the mutation in his family allows researchers to conclusively test whether Lincoln had the responsible gene. 

Lincoln’s last direct descendant, Robert Todd Lincoln Beckwith, died in 1985 along with genetic evidence that might have shed light on the question. But Lincoln’s own DNA remains possibly available in tissue samples and on items splattered with blood after his 1865 assassination. 

Although some believe the question is irrelevant to the scientific study of ataxia, Ranum and her colleagues disagree. If Abraham Lincoln were found to have carried the mutation, it would help increase awareness of this devastating disorder. 

[Note: This post is adapted from articles I have previously written about Lincoln and ataxia for the Minnesota Medical Foundation. Last month in this blog I wrote about the strange fate of Lincoln's funeral car.]