NIDA's mandate in drug abuse science is guided by a fundamental principle: our recognition that addiction is a brain disease. We know that to develop more effective prevention and treatment strategies we must deepen our understanding of how drugs affect the complex inner workings of the brain. Thanks to remarkable advances in bioscience, and particularly in the neurosciences over the past decade, this is a realistic goal. The challenge is to create from the avalanche of new data a coherent picture of biological events interacting with environmental factors and eventuating in the dysfunction we call addiction. Our Brain, Behavior, and Health Initiative, begun this past year, is a comprehensive strategy for realizing this vision.

The way the brain works can be analyzed from a number of perspectives. At the foundation are genes, where enormous progress has been made with the mapping of both mouse and human genomes and the sequencing of functional units within them. Genes build proteins, whose structure and function are elucidated by another burgeoning scientific discipline, proteomics. Proteins and the reactions between them operate within cells, a separate field of study. The cells that make up the organ of the brain form circuits and pathways—the province of neurobiology. And the consequence of activity along these brain pathways is the full range of thought and action we call human behavior.

The reality is far more complex than even this analysis suggests. Not only do genes affect proteins and cells, brain circuits and behavior, but events on the level of behavior (such as drug taking) influence brain circuits, proteins, and genes. We cannot understand the brain fully by looking only at its parts, and the ultimate aim is a unified vision of the brain.

The more we know about the brain at each level, the greater the depth and detail in which we can study addiction. For example, specifying which genes are switched on when an individual becomes addicted to cocaine, how these genes interact and affect the development of new proteins, and how these proteins alter cellular function might guide research toward novel kinds of pharmacotherapy. We know that signaling between the ventral tegmental area and the nucleus accumbens constitutes a major brain pathway stimulated in addiction to cocaine and other drugs of abuse. A deeper understanding of this system could pave the way to a different set of intervention strategies.

Clearly, what is needed is a radical departure from the traditional scientific landscape of researchers working within the isolation of separate disciplines: geneticists identifying genes in a small area of tissue, proteomics researchers focused on single protein complexes, neurobiologists probing brain circuits—each group speaking its own language within its own closed circle.

To navigate this vast and varied territory, we need a map, and the first big step of the NIDA Brain, Behavior, and Health Initiative has been to create one: the brain project matrix. Developed by NIDA health scientist administrators, the matrix brings together an immense amount of information in a computer-interactive chart, divided into sections that correspond to the five areas that represent the entire field of neuroscience research: genes, proteins, cells, brain circuits and pathways, and behavior.

For each area, key questions are set forth. For genes, for example, what is the genetic basis of brain function and behavior? How and under what conditions do genes function differently in different parts of the brain? How do gene variants, subtly different versions of the same gene, impact brain function and disease?

The matrix then captures the scientific approaches used to address each question and lists the major research centers, consortia, Government agencies, university programs, and private companies that are engaged in this work (including some, like the Department of Energy, whose research is not explicitly biological in nature). Many of these listings are hyperlinked to Web sites where the details about the program, and in some cases many of its data, can be accessed. The next column of the matrix lists the current technology applied to exploring the question, and the last indicates the technology and other resources needed to pursue answers more fully.

Simply moving among sections of the matrix conveys the multidimensional depth and breadth of neuroscience. Researchers can survey ongoing projects relevant to their work, in their own and other disciplines. Policymakers and others charged with planning and developing the research enterprise can assess more deftly the needs of the future. The matrix is a work in progress. To bring the full light of neuroscience to bear on research into addiction and other brain diseases, a future map will have to make data from diverse disciplines broadly accessible and comprehensible—a neuroinformatics effort that will bring computer scientists and mathematicians into the mix. The task is just beginning, and NIDA is proud to be at its cutting edge.

Volume 19, Number 2 (July 2004)