Defining the Genetics and Biochemistry of Wilson's Disease

A small amount of copper ingested in food is important for healthy nerves, bones, and collagen in the body. Normally the liver eliminates any excess copper through bile. But people with Wilson's disease accumulate copper in blood cells and in the liver, brain, and other organs, leading to anemia, cirrhosis, and neurological problems that can be fatal if untreated. First described in 1912, Wilson's disease was thought to be inherited, but the details remained uncertain because no one had taken careful family medical histories of patients with this rare disorder. In the early 1950s, Alexander Bearn (1923-2009) studied patients with Wilson's disease at the Rockefeller Hospital and determined conclusively that it is inherited as an autosomal recessive trait. He also studied the biochemistry of copper metabolism in these patients.


Bearn, Alexander

Bearn studied 26 cases of Wilson's disease in 16 families. Family pedigrees revealed a high rate of first cousin marriage among the parents of Wilson's disease patients, with none of the parents affected-two clues that the disease was recessively inherited. The genetic ratios of affected and unaffected family members provided additional support for this idea. In addition, Bearn studied metabolic abnormalities associated with Wilson's disease, which could also be used to diagnose it-high levels of copper and certain amino acids in the urine, and a low level of copper (measured as ceruloplasmin) in the blood. Bearn's findings suggested that, along with limiting copper in the diet, agents to chelate the metal and remove it from the body could be effective therapies for Wilson's disease, making it one of the first genetic diseases that could be diagnosed and treated. Some 40 years later, the gene that is defective in Wilson's disease was discovered. It encodes the protein ATP7B, which helps transport copper to the bile and incorporate copper into ceruloplasmin, which carries it through the blood. 

Alexander G. Bearn received the MB, BS, and MD (1950) from the University of London. In 1951 he joined the Rockefeller laboratory of Henry Kunkel, and in 1964 he became head of his own laboratory at Rockefeller. Two years later he moved to Cornell University Medical College where he served as chairman of the department of medicine as well as physician-in-chief of New York Hospital. With colleagues at Rockefeller, Bearn initiated a joint MD/PhD program at the two institutions. In 1979 he joined Merck & Co. and was senior vice president for medical and scientific affairs of its international division until 1988. Bearn served Rockefeller as a trustee from 1970 to 1998, when he became emeritus. He also was a trustee of the Howard Hughes Medical Institute (1987-2005) and executive officer of the American Philosophical Society (1997- 2002), as well as a trustee of the Helen Hay Whitney foundation and the Josiah Macy Jr. Foundation, and an overseer of The Jackson Laboratory. Bearn was an elected member of the U.S. National Academy of Sciences (1972) and its Institute of Medicine. He also was a member of the American Philosophical Society (1972), the Harvey Society, and the American Society of Human Genetics, which he served as president in 1971. A prolific writer with an interest in the history of medicine, Bearn authored three scientific biographies (see Further Reading).

Selected Publications

Bearn AG. Genetic and biochemical aspects of Wilson's disease. Am J Med, 1953, 15: 442-449

Bearn AG and Kunkel HG. Biochemical abnormalities in Wilson's disease. J Clin Invest, 1952, 31: 616
http://www.jci.org/articles/view/102648/pdf

Bearn AG. Wilson's disease. Am J Clin Nutr, 1961, 9: 695-699

Further Reading

Wilson SAK. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain, 1912, 34: 295

Bearn AG. Archibald Garrod and the Individuality of Man. Oxford Univ Press, 1993

Bearn AG. Sir Clifford Allbutt (1834-1925): Scholar and Physician. London: Royal College of Physicians, 2007

Bearn AG. Sir Francis Fraser: A Canny Scot Shapes British Medicine. Book Guild Publishing, 2008