Decoding Darkness: The Search For The Genetic Causes Of Alzheimer's Disease

by Rudolph E Tanzi, Ann B. Parson

Overview

Working from the intriguing hypothesis that Alzheimer's dementia is the result of a renegade protein-beta amyloid-Tanzi and others set out to find the gene responsible for its production. Decoding Darkness takes us deep into the minds and far-flung labs of many a prominent researcher, offering an intimate view of the high stakes of molecular genetics, the revolution that propels it, the obstacles that threaten to derail it, and the families whose lives are so dependent upon it. Tanzi and Parson ultimately reveal that Alzheimer's, like heart disease, may be effectively treated-even prevented.

Product Details

ISBN-13:	9780738205267
Publisher:	Basic Books
Publication date:	12/27/2001
Pages:	304
Sales rank:	366,628
Product dimensions:	6.12(w) x 9.25(h) x (d)
Lexile:	1320L (what's this?)

About the Author

Rudolph E. Tanzi is Professor of Neurology at Harvard Medical School and Director of the Massachusetts General Hospital's Genetics and Aging Unit.

Science journalist Ann B. Parson is co-author, with Isaac Schiff, M.D., of Menopause, and until recently taught in Boston University's graduate program in science and journalism.

Read an Excerpt

Chapter 1: Cleave, Zap, Blot, Probe

At twenty-one and fresh out of college, I entrusted myself to the Taoist philosophy that the less you interfere in Nature's course, the more likely you will find your true path in life. This wisdom flowed from a slip of a book I'd discovered in high school-the Tao Te Ching. In retrospect, it would seem that giving myself up to "the way of things" succeeded, because that fall, out of the blue, an opportunity of a lifetime presented itself, one that introduced me to a spectacular new scientific method and later prompted my investigation into the genetic wrongs of Alzheimer's disease.

It was a cloudy September Saturday in 1980, and after the quiet of summer, Boston seemed energized by autumn's return. Beacon Hill's narrow streets were clogged with cars, its crooked-brick walks filled with residents and students who seemed all business. On the Charles River even the sailboats crossing the watery line between Boston and Cambridge flew forward at a clip. A few blocks east on Blossom Street, which curves behind Massachusetts General Hospital, members of the rock band Fantasy and I moved more like laden barges. Sleep-deprived and hungover from the previous night's fling, we nonetheless managed with an elevator's aid to move the band's musical equipment into the Flying Machine, the nightspot atop the Holiday Inn that attracted everyone from visiting Portuguese sailors to the occasional Brahmin.

Four months earlier, in May of 1980, the University of Rochester had sent me into the world with what I hoped would be sufficient padding bachelor's degrees in both history and microbiology. The one, Time Past, had filled me with an indelible impression of the patterns and trends that span recorded centuries. The other, Emergings of Time Future, had left me startled by the phoenix soaring out of the present-the molecular-genetics revolution. Biology's horizon was filled with elaborate possibilities far beyond the imaginings of such tour-de-force microbe hunters as Louis Pasteur, Robert Koch, and Paul Ehrlich.

In the course of my history studies, I'd devoured Thomas Kuhn's The Structure of Scientific Revolutions and taken away his valuable model. One set of beliefs ascends over time, then falls under the weight of a crisis, which inevitably ushers in yet another belief system that rises and similarly collapses, and so on, until there's a sense, as from a wave rolling forward, that you can extrapolate the nature of the next crisis and the new visions it will unfold. Now a scientist, I'm even more aware that the models we put our faith in are mostly wrong. Someday they will be as outmoded as the idea, imagined by Franz Mesmer in the eighteenth century, of how to relieve people of disease: Stand them across from healthy folk in a tub of water, have both groups grasp a long metal chain, and let the positive forces of animal magnetism flow from the healthy into the infirm, miraculously curing them. For scientific revolutions to take flight, current theories have to be questioned, the status quo disrupted. Since my years at Rochester, I've always wanted to induce the next crisis, inspire the next paradigm shift. This is the challenge of science-to shed dogma and get closer to the truth.

But scientific revolutions were the furthest thing from my mind that Saturday atop the Holiday Inn. I was in the throes of a postcollege existentialist crisis. Why did I exist? What was life? Living life as a bushyhaired, scruffy musician and playing keyboard once again with my musician friends from high school days seemed the best way to regain some perspective. When I was ten, my Uncle John had let me fold and unfold the huge red accordion he played in old-age centers around our hometown of Cranston, Rhode island, and from then on I'd been glued to the keys of pianos, electric organs, and synthesizers. Blues, jazz, rock, punk, improv, some classical. One form fed another. I'd come to realize that when I played music on a daily basis-even on an informal basis, as I had throughout college-life was always better. When I didn't, disaster struck...

Table of Contents

	Introduction	xiii
1	Cleave, Zap, Blot, Probe	1
2	The Core of the Matter	21
3	Candidate Chromosome	49
4	Gone Fishing	61
5	Curious Gene	85
6	From Famine to Feast	99
7	Mutations, Revelations	115
8	Of Mice and People	135
9	Gene Prix	147
10	The 42 Nidus	173
11	Untangling a Cascade	191
12	A Gamble for Hope	207
	Epilogue	241
	Resources	249
	Notes	251
	Index	269

What People are Saying About This

Matt Ridley

With the human genome mapped, the heroic age of gene-hunting is over...Rudy Tanzi was one of [its] heroes. (Matt Ridley, author of Genome)

Editorial Reviews

The story is invigorating, the progress is fantastic, and the writing is lively.

New England Journal of Medicine

So infectious is [Tanzi's] enthusiasm that, like children at a pantomime, readers happily cheer or hiss at his peculiar-sounding chemicals-especially his villain, A-beta.

Economist

At the turn of the 21st century, Alzheimer's is the fourth leading cause of death of Americans. Twenty years ago, Tanzi, now a professor of neurology at Harvard Medical School and director of Massachusetts General Hospital's Genetics and Aging Unit, worked in a study examining the genetics of Huntington's disease, and while doing so he developed a method for locating disease genes and their proteins., Starting in the 1980s Tanzi applied these methods to the search for the cause or causes of Alzheimer's, a neurogenerative disease similar to Huntington's. In this fascinating story--part mystery, part scientific treatise, and part autobiography--Tanzi recounts every step along the way of the search. His own research rests on the hypothesis that deposits of the gummy protein amyloid form millions of plaques that settle between brain cells in the cerebral cortex as the result of a genetic mutation, and he chronicles the search for the gene that contains this mutation. Tanzi's tale (told with the help of science journalist Parson) is not just another sterile account of scientific discovery, as he weaves into his narrative the poignant stories of Alzheimer's families with whom he has worked and patiently guides readers through his own process of discovery and its implications for the future of Alzheimer's patients. (Nov.) Copyright 2000 Cahners Business Information.

Publishers Weekly - Publisher's Weekly

Following Daniel Pollen's Hannah's Heirs (LJ 6/93; updated in 1996), this engrossing book is the second major account of the race to uncover the genetics behind Alzheimer's disease as told by one of its main players. Tanzi (neurology, Harvard Medical Sch.) and science journalist Parson discuss his research and the work of others that led to recent genetic discoveries associated with early-onset and late-onset Alzheimer's disease. The personal animosities and lab rivalries described here are reminiscent of the road to discovering the double helix, though Decoding Darkness lacks the crispness and clarity of James Watson's book. Tanzi and Parson also introduce a parallel thread that traces the progression of the disease in a single family, lending human interest to the subject. Written for the informed lay reader, this book will be better appreciated if the reader has some background in molecular genetics. More information on Alzheimer's is available in the "Resources" section. [Both Pollen and Tanzi are profiled in Charles Pierce's excellent Hard To Forget: An Alzheimer's Story (LJ 4/15/00).--Ed.] --Leila Fernandez, Steacie Science Lib., York Univ., Toronto, Ont. Copyright 2000 Cahners Business Information.

Library Journal

Chronicles the struggle to find causes and a possible cure for Alzheimer's disease, centering on the search for the gene responsible for the production of a renegade protein, beta amyloid. Offers a portrait of the high stakes of molecular genetics, the revolution that propels it, the obstacles that threaten to derail it, and the families whose lives depend on it. Tanzi teaches neurology at Harvard Medical School and directs the Massachusetts General Hospital's Genetics and Aging Unit. Parson is a science journalist. Annotation c. Book News, Inc., Portland, OR (booknews.com)

Booknews

Decoding Darkness charts the search for the genetic causes of Alzheimer's disease, detailing the studies which have taken place and the promising theory which could help promote new drugs in the battle against Alzheimer's. Lay readers and medical personnel alike will find this a fascinating medical detective treatise which probes molecular clues to illness and therapeutic applications.

...recommended reading for anyone interested in Alzheimer's disease.

Nature

...in all the best ways, a human account of one of the most important scientific missions of our time.

Newsday