Book Review

Cell Biology of Addiction

N Engl J Med 2006; 354:2301-2302May 25, 2006

Article

Cell Biology of Addiction
Edited by Bertha K. Madras, Christine M. Colvis, Jonathan D. Pollock, Joni L. Rutter, David Shurtleff, and Mark von Zastrow. 465 pp., illustrated. Cold Spring Harbor, N.Y., Cold Spring Harbor Laboratory Press, 2006. $125. ISBN: 0-87969-753-9

As one who deals daily with the personal tragedies of patients who have addictive disorders, I find it useful to conceptualize addiction as the “cancer of behavior.” How else could one fathom the mother who buys cocaine for herself instead of food for her children, or the patient with chronic obstructive pulmonary disease who puffs on cigarettes after inhaling oxygen, or the usually loving father who comes home in a drunken rage and beats members of his family nearly to death with a baseball bat? These examples suggest both how addiction can overwhelm all other needs of the organism and the often self-destructive trajectory of this disorder, making the analogy to cancer seem to be not at all far-fetched. The “metastasis” of addictive behavior penetrates throughout the behavioral repertoire. Moreover, for those to whom the addict is important, addiction supersedes even cancer in its consequences.

Cell Biology of Addiction, a groundbreaking and comprehensive book, describes exquisite and rigorous scientific inquiry into the molecular and cellular underpinnings of addiction, examining, as Bertha K. Madras states in the introduction, “genetic influences, biological targets of drugs, neurotoxicity, and the signaling pathways that trigger neuroadaptive processes to drive or contribute to compulsive and uncontrollable drug use, withdrawal, craving, and relapse.” The chapters are based on a course designed by leaders in the field to teach this subject at the Cold Spring Harbor Laboratory to the next generation of neuroscientists, who now have the opportunity to unravel the powerful forces that propel the addicted patient and consequently overwhelm today's society in so many ways. Madras estimates the total annual cost attributable to addictions in the United States at $544 billion. This book embodies the hope that “cellular and molecular biological research is of fundamental relevance to reducing this public health burden, by developing evidence-based insights into the etiology and neurobiology of drug addiction and contributing to novel approaches to treatment strategies.”

The emotion-laden analogy with cancer harkens back to December 23, 1971, when President Richard M. Nixon signed the National Cancer Act into law, declaring the “War on Cancer.” Addiction now carries much the same stigma and incurs the loss of life and productivity and the health care costs that were associated then with cancer, but to an even greater extent. As the biomedical community's fight against cancer led to fundamental discoveries in gene regulation, cell division, intercellular communication, and differentiation and to the development of effective medications to modify these processes, so addiction may provide the catalyst for understanding learning and memory as well as emotions and fundamental drives, and the elucidation of what motivates people both as individuals and as a society. Most important, this body of knowledge may serve finally to help physicians understand in scientific terms that addiction should be viewed as a biomedical disorder and not simply as a bad habit or as evidence of weakness of character.

Our fundamental understanding of addiction is that it is not unlike cell division gone awry. In addiction, normal human drives are overwhelmed by a desperate urge to drink or to use prescribed or illicit drugs. The pleasure involved in the use of drugs is insufficient to explain this displacement of drives. Rather, neural pathways within the brain become modified by molecular mechanisms that mediate synaptic plasticity, eventually altering the neural representations of brain functions.

The story of understanding addiction must include unraveling the complex interactions between the genome and the environment in which addiction develops. Although the structure of this book emphasizes the machinery that goes awry in addiction because of the use of drugs, rather than the contribution of the environment, it nevertheless “conveys the merits and excitement of cellular and molecular approaches to drug addiction and describes fundamental, state-of-the-art advances and major gaps in the field, as well as those within the broader context of neuroscience.”

Once we gain a better understanding of the complexities of addiction, we will come full circle back to the beginning — that is, to recognition of the role this “cancer of behavior” plays in the causation of many of the most common illnesses that affect humans, including cancer, obesity, and atherosclerotic heart disease. Readers of this exciting book will find it satisfying on two levels — the scientific and the symbolic. Scientifically, it is indeed gratifying that so much of what we have learned about the functioning of the brain has been derived from attempts to elucidate the mechanistic underpinnings of addiction. And symbolically, we have reason for optimism because of the many basic neuroscientists who are devoting themselves to the challenge of understanding a disorder that affects so many.

Peter R. Martin, M.D.
Vanderbilt University Medical Center, Nashville, TN 37232
peter.martin@vanderbilt.edu