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The aim of this paper is to present a concise account of the history, mission, structure and some recent achievements of the US National Institute on Alcohol Abuse and Alcoholism (NIAAA). Created by the US Congress 40 years ago, the NIAAA has evolved from an entity charged mainly with building a national system of alcoholism treatment services to one with responsibility for developing, nurturing and supporting the biomedical and behavioral science foundation necessary to reduce the significant domestic and global public health impact of alcohol use disorders. The NIAAA is unique in that it functions both as a funding agency, supporting research at universities and other external, or ‘extramural’ research institutions, and is also a research institution itself, where alcohol research is carried out in-house, or ‘intramurally’. Of a $450.2 million 2009 Congressional Appropriation, approximately 90% was devoted toward the former and approximately 10% towards the latter objective. The current NIAAA Strategic Plan builds on a new organizing principle for long-range research planning, based on a life-span perspective that recognizes that human biology and behavior continue to change throughout life and changes occurring throughout the life-span affect individuals’ drinking patterns as well as the decisions they may make to change their drinking habits or to seek help for alcohol use problems. Within this framework, major efforts are currently being devoted to educating practitioners on clinically useful, science-based assessment and treatment methods that exist today, and development of personalized new treatments for tomorrow.
The National Institute on Alcohol Abuse and Alcoholism (NIAAA), an institute of the US National Institutes of Health, is the lead agency for US research on the health-related impact of alcohol use. Created in 1970 by the US Congress by the Comprehensive Alcohol Abuse and Alcoholism Prevention, Treatment, and Rehabilitation Act (P.L. 91–616) , NIAAA was the first US federal agency committed exclusively to alcohol issues since the abolition of the Prohibition Bureau in 1933 . During its 40-year history, the NIAAA has seen changes to its structure, mission and organizational home and has evolved from an entity charged mainly with building a national system of alcoholism treatment services to one with responsibility for developing, nurturing and supporting the biomedical and behavioral science foundation necessary to reduce the significant domestic and global public health impact of alcohol use disorders. In this paper we will provide an overview of NIAAA’s history and evolution, and discuss its current mission, organization, budget and scientific activity. We were asked to provide a sense of how the Institute is likely to function and develop over the next 5 or 10 years. This discussion may be moot; as of writing, the Institute is facing questions as to whether science might be better served by folding alcohol into an organization with broader responsibility for the study of addictive disorders. These are not new questions; such have been raised, studied and ultimately discarded three times over the course of NIAAA’s history. However, as the answers to these questions may change profoundly the structure and function of NIAAA, we will withhold commentary on these aspects of the Institute’s future and confine our comments to the continued evolution of alcohol science over the near term.
NIAAA’s creation in 1970 represented the culmination of a decade’s long struggle by recovering alcoholics to achieve national recognition of alcoholism as a medical condition, rather than a moral failing. Although support for medical research in general was in ascendance during the post-World War II era, alcohol problems were still seen largely as moral problems requiring punitive rather than medical treatment. The success of Alcoholics Anonymous (AA), founded in 1935, demonstrated that alcoholics could recover, providing a crucial impetus to acceptance of alcohol use disorders as health problems. Beginning in the 1950s, major health care organizations, such as the American Medical Association and the World Health Organization, had begun to address health care aspects of alcoholism, supporting further the transition to medical/scientific acceptance of alcohol problems as health problems. In the late 1960s, a number of prominent individuals influential in business and industry, many of whom were recovering alcoholics, coalesced around a United States Senator, Harold E. Hughes, himself a recovering alcoholic, to advocate for legislation to create this federal entity. As noted by Senator Hughes, ‘Establishing NIAAA to provide national leadership in the alcohol field’ involved ‘dozens of recovering alcoholics, their family members, treatment professionals, and researchers who risked everything to stand up with me and make their voices heard … the stigma associated with alcoholism was so great in the early years that we [individuals involved in advocating for legislation] were literally putting our reputations on the line’ .
Created by P.L. 91–616 as an Institute within the National Institute of Mental Health (NIMH), in 1973 NIAAA became one of three Institutes of a newly created agency, the Alcohol, Drug Abuse and Mental Health Administration (ADAMHA) along with NIMH and a National Institute on Drug Abuse (NIDA). Initially, NIAAA was charged primarily with developing and supporting treatment and prevention services and clinical training. Although research was clearly intended in NIAAA’s authorizing legislation, for almost a decade support for scientific investigations and investigators took a back seat to establishing a national system of community-based alcohol programs and developing the human resources to serve it. By the late 1970s, the United States had assumed the principal responsibility for developing and monitoring community-based services programs and NIAAA’s mission shifted to focus increasingly on science and on disseminating scientific information. This shift was accelerated between 1981 and 1986 when funding for NIAAA, NIDA, and NIMH service programs was transferred to a block grant program. (Block grants provide funds to the States based on a formula, providing each State the flexibility to manage its own alcohol, drug, and mental health programs.) In 1992, ADAMHA was abolished by the ADAMHA Reorganization Act of 1992 (P.L. 102–321), and NIAAA (along with NIDA and NIMH) was transferred to the NIH. Our evolution into a science institute is now fully realized. NIAAA research dollars have grown from $9.2 million in 1971 to $171.5 million in 1992, the year of transition to NIH, to our current funding level of $450.2 million. A comprehensive account of the history of NIAAA’s evolution is described in our previous research center report for this journal .
NIAAA is one of 27 Institutes and Centers of the National Institutes of Health (NIH), which is a part of the US Department of Health and Human Services. The Institute is comprised of two major components, one providing support for extramural research primarily through grants and contracts to individual investigators and collaborative research centers, the other supporting science through in-house laboratories. NIAAA receives its annual operating budget as a part of an appropriation for the NIH from the US Congress. Some portions of the NIAAA budget (as is the case with all NIH Institutes) is provided for cross-cutting projects initiated by the Office of the Director, NIH. NIAAA’s current organization is shown in Fig. 1 and described below. The budget for fiscal year (FY) 2009 is $450.2 million; a comparison of NIAAA’s appropriated budget with that of other NIH Institutes and Centers is shown in Fig. 2.
The Office of the Director leads the Institute by setting research and programmatic priorities and coordinating cross-cutting initiatives. Three staff offices provide long-range planning, coordination of activities that cut across Divisions and day-to-day management of the Institute on behalf of the Director.
The intramural research component of NIAAA is a single Division, the Division of Intramural Clinical and Biological Research (DICBR). In terms of number of personnel DICBR is the largest division in NIAAA, but its budget is about only about 10% of the Institute total. An intramural research budget of about 10% of an Institute’s budget is roughly average for those NIH Institutes that have intramural programs. The DICBR is comprised of 10 laboratories, most of which are divided further into sections/units. The chief of each laboratory is a doctoral-level scientist who is tenured at NIH. Sections/units within laboratories are also headed by doctoral-level scientists, some of whom have achieved tenure (and are section/unit chiefs) and some of whom are not yet tenured but are on tenure track (and are section/unit acting chiefs). The process of achieving tenure at NIH involves rigorous review by a board of outside scientists expert in the relevant field(s) and, unlike extramural grant review, past scientific achievement is weighted much more heavily than future plans in reaching the tenure decision.
The DICBR has as its overall goals understanding the biological basis of alcohol use disorders and alcohol-induced morbidities, and developing novel strategies and tools for the prevention and treatment of these disorders. Research is conducted at multiple levels: cellular/molecular, animal studies in rodents and non-human primates, human studies of the genetics and epidemiology of alcoholism and comorbidities and validation of novel molecular targets for alcohol use disorders. Collaborations among the various units and between these units and investigators from other NIH institutes or extramural institutions reflect the integrative, multi-disciplinary nature of ongoing research. Research into the causes and consequences of alcoholism is not a discipline in its own right; rather, it relies upon and employs the tools of a wide range of biological disciplines. The outstanding scientists heading the various research units of our intramural program are recognized for their contributions to their chosen research fields, be it molecular biology, neuroscience, biochemistry, physical chemistry, physiology, genetics, epidemiology or psychiatry, and apply their expertise to answer questions related to alcohol use disorders.
The Laboratory of Clinical and Translational Studies (LCTS) is the primary clinical laboratory of our intramural program. It focuses upon developing novel pharmacological treatments for alcohol use disorders through a combination of pre-clinical studies aimed at discovering and validating new molecular targets using rodent and primate models, and clinical proof-of-concept studies that test these novel targets through the use of therapeutic agents directed against such targets. This work also takes advantage of state-of-the-art functional brain imaging techniques. Through agreements with industry partners, LCTS has been able to leverage government dollars and gain access to compounds of interest that would otherwise have been unattainable. None the less, due to budgetary constraints, the NIAAA contribution to NIH’s long-standing primate research program had to be ended in FY 2007.
The Laboratory of Membrane Biochemistry and Biophysics (LMBB) explores the relationship between alcohol-induced changes in membrane structure and function and investigates the biological functions of polyunsaturated fatty acids, with special emphasis on docosa-hexaenoic acid (DHA). This laboratory utilizes diverse methodological approaches, ranging from spectroscopy to biochemistry and nutritional neuroscience to psychiatry.
The Laboratory of Neurogenetics (LNG) aims to identify genes that predispose to or protect from alcoholism and comorbid disorders. Their approach combines functional genomics in in vitro systems, large-scale analyses of gene expression and linkage analyses, including both candidate gene and genome-wide approaches.
The Laboratory of Epidemiology and Biometry (LEB) designs, conducts and analyzes the collected data from national epidemiological surveys on alcohol use disorders and related conditions, in order to gain insight into their prevalence, comorbidities, prevention, treatment needs and societal costs.
The unifying theme of research in the Laboratory of Integrative Neuroscience (LIN) is forebrain mechanisms of cognition and behavioral control that play a role in addiction, which are investigated using a combination of electrophysiological, cell and molecular biological and whole animal behavioral techniques and paradigms.
The Laboratory of Molecular Signaling (LMS) explores the signaling pathways involved in the effects of poly-unsaturated fatty acids on neuronal survival and their modulation by ethanol, using a combination of cell biological and mass spectrometry-based proteomic approaches.
Research in the Laboratory of Physiologic Studies (LPS) focuses upon neuroendocrine mechanisms that regulate appetitive functions, including alcohol drinking behavior, on liver biology and on mechanisms of oxidative and nitrosative stress. A shared interest among the three sections of this laboratory is the role of the endocannabinoid system in the above functions.
The Laboratory of Metabolic Control (LMC) studies how the flux through various metabolic pathways is involved in controlling cellular energy status, with particular emphasis on the metabolism of ketone bodies and its therapeutic implications.
The Laboratory of Molecular Physiology (LMP) investigates cellular, subcellular and molecular mechanisms underlying synaptic transmission in the nervous system, using electrophysiological and advanced cellular imaging techniques, as well as zebrafish genetics.
Finally, the Laboratory of Neuroimaging (LNI) uses in vivo brain imaging to gain insight into the neurochemical basis of addictive disorders, including drug-seeking behavior, alcoholism and alcohol dependence. It is unusual that the chief of the LNI is the Director of another NIH Institute (NIDA); NIH requires that an Institute Director’s intramural laboratory be located administratively in another Institute to avoid a potential for conflict of interest. As is common among all NIH research institutes, LNI staff interacts scientifically with other DICBR and NIH researchers.
NIH, including NIAAA, is very much engaged in the training of future scientific leaders. In addition to its primary research role, the NIAAA Intramural Program has an active training program with trainees at undergraduate, post-baccalaureate, graduate and postdoctoral levels. Trainees come from throughout the US and many other countries through a variety of training mechanisms; at any given time, there are a 100 or more trainees working in DICBR laboratories.
After a period of rapid budgetary growth (‘the doubling’) the NIH budget has been flat for a number of years, with budget growth less than inflation. The DICBR budget has paralleled that of NIH. Despite the budgetary pressure, research productivity has reached new highs in the intramural program. Recent significant scientific advances illustrate this fact, and also the broad and interdisciplinary scope of the research:
The key to continued success in the DICBR lies in the creative ingenuity and hard work of our investigators who are guided by the principle enunciated by the Nobel laureate, Albert Szent-Györgyi: ‘Discovery consists in seeing what everyone else has seen and thinking what no one else has thought’.
The NIAAA Extramural Research Program consists of four Divisions, each focusing upon a specific scientific area: epidemiology and prevention research, metabolism and health effects, neuroscience and behavior, and treatment and recovery. The principal role of the NIAAA Extramural Divisions is to provide ongoing support for NIAAA-funded investigators and to create opportunities for enhanced and expanded areas of investigation. NIAAA’s current extramural research portfolio is shown in Fig. 3. The research areas for which the extramural divisions have responsibility are briefly described below along with each Division’s FY 2009 budget.
DEPR supports research on the etiology and course of alcohol use disorders (AUDs) and the relationship of alcohol consumption and AUDs to unintentional and intentional injuries and other diseases and disorders and on the efficacy and effectiveness of a variety of individual, family-, school- and community-based prevention interventions ($83.8 million).
DMHE deals with basic research aimed at expanding understanding of the genetic, metabolic and immunological mechanisms involved in alcohol-induced tissue injury and alcohol’s potential beneficial effects. Among the objectives is to develop biomarkers for the early stages of disease, and medications to prevent or treat alcohol-induced organ damage ($73.6 million).
DNB focuses upon research investigating neuronal and behavioral systems and how these are influenced by genetic, developmental and environmental factors to produce harmful drinking and alcohol dependence, including how neurobiological processes promote the initiation and maintenance of drinking and the subsequent neuroadaptative changes leading to excessive alcohol use dependence. The Division also supports pre-clinical research to identify compounds that may be effective therapeutic agents in preventing/treating alcohol use disorders and research factors that mediate behavioral responses such as alcohol dependence, tolerance, sensitization, withdrawal and relapse ($129.9 million).
DTRR supports research, the bottom line of which is to improve how alcohol use disorders are treated clinically and recovery supported to prevent relapse to harmful drinking patterns. DTRR’s research responsibilities include understanding mechanisms of behavioral change; models of disease management for chronic alcohol use disorders and comorbid medical or mental disorders; health services research, including the impact of alcohol-related services on health care economics; the implementation of evidence-based practices and quality improvement in treatment settings; and the development of medications that diminish the craving for alcohol and reduce risk of relapse ($65.9 million).
During NIAAA’s last major reorganization (2003) several transdisciplinary teams were established to enhance collaboration across NIAAA. These teams are flexible, being formed or disbanded as research needs dictate. Two significant outcomes of this cross-pollination have been the acceleration of NIAAA’s medications development efforts and a major initiative reaching across US Federal agencies to prevent underage alcohol use and the consequences of that use. Current transdivision teams are shown in Fig. 1.
Alcohol use disorders are significant global health problems, and NIAAA has an ongoing program of international collaborative research to facilitate improved knowledge and care in this area. For example, NIAAA has an active program of scientific exchange with the French Institut National de la Santè et de la Recherche Mèdicale (INSERM), and has signed letters of intent to foster research cooperation and scientific exchange with the National Institute on Alcoholism in Japan; the Peking University Institute of Mental Health and the Institute of Nutritional Sciences in Bejing, China; the National Health Research Institute in Taiwan; and the South Korean Centers for Disease Control and Prevention.
In 2006, NIAAA introduced the NIAAA Strategic Plan for Research, a new organizing principle for long-range research planning based upon a life-span perspective that recognizes that human biology and behavior continue to change throughout life, and changes occurring throughout the life-span affect individuals’ drinking patterns as well as the decisions they may make to change their drinking habits or to seek help for alcohol use problems. The Plan focuses research attention upon alcohol problems among across segments of the human life-span (the fetus, childhood, adolescence, young adulthood, middle-age and seniors). Included in the strategic plan are lifespan-transcending themes—scientific issues that impact all stages of life, but affect individuals differently depending upon the life stage. These include alcohol metabolism, genetic and environmental influences including epigenetics, neurobiological effects of alcohol and improvements in the diagnostic recognition of alcohol use disorder. Planning occurs annually and includes input from NIAAA’s intramural and extramural divisions, staff offices, National Advisory Council on Alcohol Abuse and Alcoholism and panels of distinguished scientists, who review individual areas of research to recommend future research priorities.
The most important mechanism through which NIAAA as a funding agency can nurture scientific creativity and excellence is by emphasizing the investigator-initiated nature of the research it supports. NIAAA has been able to impact positively the inherently multi-disciplinary field of alcohol studies by attracting the best academic researchers from a diverse range of areas to the field and funding their best ideas, be they in the realm of neuroscience, genetics or elsewhere. The alcohol research centers that NIAAA funds take the same concept to another level. These centers provide incentives for the best scientists to come together in thematic constellations that benefit from the interactions between the investigators, and from building a joint infrastructure. Finally, the same approach permeates the ‘virtual centers’ that NIAAA supports, such as the Collaborative Studies on Genetic of Alcoholism (COGA), the two Integrative Neuroscience Initiatives on Alcoholism (INIAs) and the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), which aim to create the same type of synergies across geographical space. In each of these mechanisms, the content of the research remains determined by the best ideas of the scientists, as evaluated by their peers. This reflects the philosophy that only one thing can be known about the best research results of tomorrow: that we do not know them today. By applying these strategies, the NIAAA has been instrumental in transforming alcohol research into a highly competitive field, where some of the most important advances of, e.g. addiction neuroscience have been achieved in the last decade.
The research carried out within the NIAAA intramural program reflects the same basic strategy, but adds some critical components. The first of these is the ability to pursue scientific ideas that are inherently ‘high risk/high gain’. Because of the unique, retrospective nature of review through which intramural investigators are evaluated, they can move quickly to pursue ideas that are unorthodox. It is understood in this setting that a certain amount of failure is inevitable. If hypotheses that are evaluated are not frequently disproved, they are unlikely to be innovative enough. Secondly, a hallmark feature of the intramural program is the presence of well-integrated basic science and clinical research groups. This greatly facilitates translational research, as exemplified by the identification of novel molecular targets for pharmacotherapy, both for modifying the drive to drink and for attenuating its pathological consequences. The availability of advanced imaging and genetic methodologies (e.g. parallel deep sequencing) to our intramural researchers make the program ideally suited for mechanistic or proof-of-principle studies, whereas large, Phase III studies are best conducted in the extramural environment. A third component that adds to nurturing scientific creativity in the intramural program is that it is immersed in an environment that is built up collectively by intramural programs across the NIH institutes. The conceptual and methodological richness of that environment, on and around the NIH campus, is truly unique world-wide. It creates a critical mass where new ideas can be born, and hypotheses that were impossible to evaluate yesterday can be addressed. It also facilitates translation by providing access to NIH-wide mechanisms such as, e.g. the Rapid Access to Interventional Development (RAID) program, which facilitates proof-of-principle studies of novel compounds by providing the toxicology evaluation required by the Food and Drug Administration.
NIAAA-supported research has not, to date, produced a cure for alcoholism. For those of us who realize the chronic, relapsing nature of this disease, and its many biological, social and psychological determinants, frequently expressed hopes for such a cure frankly appear naive. Nevertheless, NIAAA-supported research has had an impact in the real world in more areas than can be covered here, and a few examples will have to suffice. Knowing the extent of a problem is the beginning of addressing it, and outstanding NIAAA supported epidemiology research provides that knowledge. NIAAA-sponsored research has also been critical to creating an awareness about alcohol as a risk factor, perhaps most importantly for the unborn fetus. A critical factor in addressing alcohol problems is getting away from widespread moralizing attitudes that blame the problems on character flaws. Research funded by the NIAAA has provided decisive evidence for a key role of genetic susceptibility factors, which effectively prompts a realization that blaming the patient is not only unproductive, but also unwarranted. Next, NIAAA-supported research has been translated into highly practical tools for effective clinical evaluation of patients and manual-based behavioral interventions. Finally, the neuroscience of alcohol addiction has established several key neurobiological mechanisms underlying excessive alcohol use and relapse to this behavior. Novel mechanisms involved in alcohol-induced tissue damage have also been uncovered that have provided druggable targets and novel chemical compounds that target them selectively for therapeutic gain. The wave of the near future is an ongoing translation of these findings into medications that can facilitate recovery and alleviate alcohol-induced tissue injury. Over the last 5–7 years, several innovative pharmacotherapy mechanisms have advanced quickly from animal studies to early human evaluation, and appear promising.
The NIAAA is an agency of the US government, and ultimately the American people. Its overall charge is given by Congress, and input from the field is continuously provided by a National Advisory Council. The direction of the institute can therefore never reflect the vision of a single individual, or group of individuals. Instead, rather than pursuing any narrow agenda, the role of directors, staffers and investigators is to amalgamate the input from these stakeholders with the best possible science, with the ultimate goal of addressing the unmet medical needs created by alcohol use and alcohol use disorders. This is certainly different from a more focused approach that could be taken by a smaller entity, or one funded by other means. Nevertheless, we believe the NIAAA has been a key force in transforming alcohol research world-wide, and attracting the best scientists to focus upon addressing the needs of people with alcohol problems.
NIAAA-supported biomedical and behavioral research is well positioned to make a major contribution to reducing the national and global burden of harmful drinking. Ongoing studies, as well as new initiatives, will provide the scientific knowledge and tools, especially biomarkers and epigenetic information, to improve our ability to predict individuals at increased risk for alcohol dependence and other alcohol-related problems, pre-empt the harm from alcohol misuse and provide personalized treatment.
Areas that we believe will continue to be highly productive include the development of teaching and training tools, such as NIAAA’s ‘A Clinician’s Guide: Helping Patients Who Drink Too Much’ (http://pubs.niaaa.nih.gov/publications/Practitioner/CliniciansGuide2005/clinicians_guide.htm), to move dealing with alcohol problems more firmly into the primary health care system. We will also continue to place a priority on our robust medications development program. Emerging data are changing the way we look at alcohol dependence, thereby guiding us to be more strategic about the medications we test, the way we test and design them and how we determine the subpopulations of patients who are most likely to benefit from them. NIAAA will also continue to investigate the process of leading to a decision to stop drinking or to seek help. The Institute is currently supporting studies to understand mechanisms of change in regard to alcohol as well as other behaviors that are harmful to health. Given our current state of knowledge and what we are learning from ongoing studies, the outlook for the future is bright. We can reduce substantially the burden of illness for alcohol-related problems, and our research is showing us how.
Declarations of interest