Book Review

Hannah's Heirs: The Quest for the Genetic Origins of Alzheimer's Disease

N Engl J Med 1993; 329:1972-1973December 23, 1993

Article

Hannah's Heirs: The Quest for the Genetic Origins of Alzheimer's Disease
By Daniel A. Pollen. 296 pp., illustrated. New York, Oxford University Press, 1993. $25. ISBN: 0-19-506809-2

Scientific truths are rarely learned instantaneously except in the movies. Nowhere is this lesson more evident than in Alzheimer's disease. Like many other neuropsychiatric disorders, it has defied attempts to unravel its biologic basis despite increasing public awareness and considerable attention from clinical and basic scientists. In the past few years, research on the proteins found in the brains of victims of Alzheimer's disease has engendered much debate about its pathogenesis and the possibilities for early diagnosis and treatment. Since 1991, when a team of British and American scientists reported their discovery of a defect in the beta-amyloid protein precursor (APP) gene on chromosome 21 in patients from two families, molecular geneticists have raised expectations that an understanding of the cause of this disorder is within reach. In Hannah's Heirs, Pollen has captured this excitement in an emotional and colorful tale of one family's struggle with this devastating disease.

The tale of Hannah, a 19th-century Russian woman who is identified as the source of familial early-onset dementia in a large kindred spread over two continents, is recounted in parallel with the history of modern genetics and the recognition of Alzheimer's disease as an organic brain disorder. By linking the plight of Hannah, a contemporary of Gregor Mendel and Alois Alzheimer, and her descendants to emerging scientific disciplines, Pollen advances a plot familiar to moviegoers and doctors alike: the patient cannot be saved, but there is hope for the next generation. Hannah's grandson Charles, a doctor who apparently escaped the family curse, is the protagonist who rallies both his family and many of the world's leading researchers to find the cause of this dreaded disease. Pollen, who collaborated with one of the teams of geneticists actively pursuing the genes for the disorder and who was physician of several of Hannah's affected descendants, made it possible for her family to become key participants in research leading to the localization of the gene causing their illness (to chromosome 14).

But the story is not as upbeat as most would prefer. Pollen offers a penetrating look at the ongoing conflicts involved in scientific research when prestige and funding are on the line. However, he does not give detailed attention to the specifics of the disputes between the investigative teams (which were discussed in an editorial in the Journal of NIH Research [1992;4:34]), and his message in this chapter thus appears diluted.

Hannah's Heirs is divided into three parts. Part I describes the history of Hannah, a Jewish matriarch whose children grew up in fear of Russian pogroms and a “biologic Holocaust,” and the work of Mendel and Alzheimer, which bears greatly on Hannah's story. Part II traces her descendants and describes classic developments in genetics and research on Alzheimer's disease from 1900 to 1980. Pollen's fine weaving of scientific facts with intriguing glimpses into the personal lives of the researchers will probably be unappreciated by readers lacking background in genetics. The foundations depicted in these middle chapters seem trivial by comparison with the leaps in the research that emerge in Part III. For example, Pollen focuses much attention on the search for Hannah's descendants who did not emigrate to America. Although it is rewarding to see the branches of the family reunited, I was selfishly disappointed to learn that the disease did not penetrate this branch, realizing that they would not be useful to the search for the gene.

When the hunt for the gene intensifies in the final chapters, it is apparent that Hannah's family is important but by no means the solitary family in the work of Pollen and his colleagues. There are glimpses of the other “Hannahs” in Italy, Nova Scotia, and Russia, including another large Jewish family that probably shares ancestors with Hannah's. The ending of the book is certainly not the conclusion of the story. The finale awaits the discovery of the culprit gene and elucidation of its aberrant properties. We can only hope that these advances are made before a new generation of Hannah's heirs succumbs to the family curse.

Lindsay A. Farrer, Ph.D.
Boston University School of Medicine, Boston, MA 02118