35th International Medical Advisory Group Conference

Halifax, Nova Scotia—October 14–16, 2007

The 35th International Medical Advisory Group Conference (IMAG) was hosted in October by ABMRF/The Foundation for Alcohol Research in conjunction with the Brewers Association of Canada (BAC) in Halifax, Nova Scotia. In 1982, the 10th IMAG was also held in Halifax, marking the first of these meetings at which ABMRF existed as an independent foundation rather than the predecessor advisory committees which had represented the U.S. and Canada. The 1982 IMAG also formalized ties between the Canadian and U.S. delegations, whose representatives joined under the banner of ABMRF to discuss many of the same issues relevant in the field of alcohol studies today. In his remarks during the meeting, Foundation President, Dr. Mack Mitchell, noted that for over 35 years the IMAGs have helped solidify our understanding of how alcohol affects health and behavior and to identify exciting new areas and trends in alcohol research. Moreover, they have provided a unique opportunity for building effective working relationships between biomedical and behavioral scientists and for promoting the partnership of academia and industry in seeking new knowledge regarding the effects of alcoholic beverages.

A theme of this IMAG was to illustrate how scientific knowledge is developed as research is advanced from one generation of investigators to the next through training and mentorship. Several examples of research “lineage” were presented by having investigators representing different generations highlight their work showing how each new discovery is derived from earlier work. Many presentations were made by current or former grantees or members of the Foundation’s Advisory Councils. In the last 15 years, ABMRF has made a concerted effort to identify and support promising new investigators in alcohol studies and they were well represented this year. The multi-generational theme was also evident in the brewing industry by the participation of both Derek Oland of Moosehead Brewery and his son, Andrew, the company’s sixth generation. The late Philip Oland, Derek’s father, helped host the 1982 Halifax IMAG and provided many delightful stories about the city’s history.

This year’s IMAG was opened by BAC President, Ian Faris. The first session featured highlights of ABMRF-sponsored research examining how the metabolism of alcohol and its metabolite acetaldehyde might contribute to the risk of alcohol use disorders (AUD) and alcoholism. Dr. David Crabb, a member of the Medical Advisory Council (MAC) and professor at Indiana University, started the session by discussing alcohol and aldehyde dehydrogenases, the enzymes primarily responsible for metabolism of alcohol and the risk of alcoholism. His review of these enzymes and how they might influence overall risk of alcoholism and associated disorders provided insight into understanding this important area. He also cited the work of ten previous ABMRF grantees in this area. Dr. Tamara Wall from the University of California San Diego, presented evidence for a low risk of AUD in Jewish Americans that may be related to an allele (ADH1B*2) coding for alcohol dehydrogenase. Although previous studies have hypothesized that the low rate of AUD was based on cultural and religious traits, the ADHB1*2 allele is found in a relatively high prevalence in Jewish Americans and is associated with a lower risk of AUD. Dr. Wall underscored the importance of understanding the interactions between genes and environment. Following her presentation, Dr. Crabb provided more detailed information regarding variants of ADH and ALDH2 that appear to be associated with an altered risk of AUD. In some instances, the risk is higher whereas in others it is lower. Clearly the inability to drink more than small amounts of alcohol without adverse effects is somewhat protective against developing alcoholism for many Asians who have an abnormal aldehyde dehydrogenase gene (ALDH2*2), so that acetaldehyde accumulates in relatively high concentrations following consumption of alcohol. Dr. Susan Luczak of the University of Southern California described preliminary findings correlating real-time drinking behavior in individuals with their ALDH2 genotype. Her work utilized frequent measures of breath alcohol levels during real-time drinking sessions with the hypothesis that peak blood alcohol would be significantly influenced by the ALDH2*2 genotype. The work will likely yield important findings.

In the second session entitled Building a Body of Knowledge, Dr. Sherry Stewart, a member of the Foundation’s Behavioral and Social Advisory Council (BSAC) and professor at Dalhousie University, chaired a review of the contributions of Dr. Anne-Marie Wall, a former ABMRF grantee whose presentation opened the 31st IMAG Conference in Niagara-on-the-Lake. Dr. Wall died unexpectedly in 2005. Dr. Marvin Krank, Professor at the University of British Columbia, Okanagan, described Dr. Wall’s important research contributions, her role as a mentor, and her work with collaborative studies. The session served to illustrate the value of research networks and the catalytic effect Foundation funding has had in assisting career development of promising young investigators.

Interaction between alcohol and nicotine was explored in session three moderated by Dr. Ken Sher, professor at the University of Missouri and former BSAC chair. The association between heavy drinking and cigarette smoking has long been recognized by the lay public as well as the scientific community, but the depth and impact of the association is not fully known. Three former grantees presented work on alcohol and tobacco. Dr. Kristina Jackson of Brown University presented evidence showing the relationship between smoking and drinking is bi-directional. Smokers are more likely to initiate heavy drinking and to continue heavy drinking than nonsmokers. Conversely, regular and heavy drinkers are more likely to continue smoking than non-drinkers. Furthermore, “social smokers” are more likely to engage in smoking during drinking than at any other time. Whether these relationships are due to underlying common factors is not fully understood, but is clearly important. Dr. Sherry McKee from Yale University, presented evidence linking non-daily smoking with heavy, episodic drinking, showing preliminary evidence that heavy drinking potentiates the subjective reactivity associated with smoking in a relatively inexperienced group of smokers. Dr. Julie Staley, also from Yale, used SPECT brain scanning to show gender differences with regard to the effects of alcohol and smoking on the nicotine receptor. Alcohol and nicotine have opposing effects on the receptor in women, but not in men, which may explain, in part, why women smokers report less subjective intoxication than women non-smokers when drinking alcohol. Although much remains to be understood about the interactions between alcohol and nicotine, this area of research holds important clues to understanding some long-standing observations regarding alcohol-related behaviors.

Dr. Alan Marlatt, professor at the University of Washington and former BSAC member, moderated session four featuring grantees exploring intervention. Dr. Joseph LaBrie from Loyola Marymount University presented results from his study of group social norms motivational intervention. The strategy is that one’s perceptions of the acceptability or frequency of a particular behavior among a group of peers will determine the probability of an individual engaging in that behavior. Providing feedback about the actual frequency of the behavior can have a powerful effect on the future likelihood of someone engaging in the behavior. His study extends this theory by asking members of Greek organizations on a college campus or student athletes to make decisions about potential behaviors such as high-risk drinking and then providing real-time feedback from the peer group to all its members. They found that members of the test intervention group reduced high-risk drinking behaviors. Dr. Thomas Brown of McGill University described work using ultra-brief motivational interviews to reduce recidivism among DUI recidivists who were not otherwise involved in remedial measures. He showed reductions in high-risk drinking behaviors in the intervention group compared to the control group with a technique that was both straight forward and effective in this high-risk population of drinking drivers, holding promise for use in larger populations. Dr. Brad Krevor of Brandeis University presented information about best practices for the reduction of sales of alcoholic beverages to underage drinkers by retail store clerks. His results indicate that 87% of Americans support a drinking age of 21 and do not mind waiting while clerks spend extra time verifying age-identification among potential underage customers. By using mystery shoppers, they were able to verify that training clerks in responsible retailing methods was an effective method to reduce underage sales. These findings have potential to be expanded to many outlets in the U.S. and Canada.

Dr. Fulton Crews of the University of North Carolina and MAC member, chaired session five highlighting successful career mentorship in work by grantees focused on the effects of alcohol on neural stem cells. The cells are located within the central nervous system and possess the potential to differentiate into nerve cells in the brain. These “adult stem cells” are found in specific organ systems and are different from embryonic stem cells that can develop into a multitude of different cell types. Dr. Kimberly Nixon of the University of Kentucky offered evidence that alcohol intoxication in animals resulted in a significant inhibition of neurogenesis, the process by which neural stem cells become functioning brain neurons. Interestingly, abstinence reverses this process. However, the inhibition is most significant in a model of chronic binge drinking which inhibits not only proliferation, but also survival of the neural stem cells. Dr. Tod Kippin of the University of California Santa Barbara reported that prolonged voluntary intake of alcohol in mice reduced the proliferation of neural stem cells, even in relatively mild levels of intoxication. Current studies to explore the mechanism and full impact of this observation are underway. Dr. Brian Christie of the University of Victoria presented work focused on alcohol’s effects on neural stem cells in a prenatal rat model using high alcohol levels that usually result in impaired neurogenesis in offspring. However, he presented a fascinating observation that permitting those “fetal alcohol” rats to exercise could negate many of the adverse findings. Rats born to mothers that were given large amounts of alcohol during pregnancy were less impaired when allowed to exercise than were control animals based on a variety of learning parameters. The observation implies that some adverse effects of alcohol may be reversible or modified.

On the second day, Dr. Mack Mitchell presented an overview of ABMRF’s history and mission over the last 25 years. The unique partnership between the brewing industry and the alcohol research community grew out of a shared concern about the lack of information about the health effects of moderate consumption of alcohol. Since ABMRF’s inception, the number of publications on the health effects of moderate consumption has grown from around 8-10/year to more than 250. Relying on a tradition of excellence in selecting the best scientists and investigators in both biomedical and behavioral research to serve on its Advisory Councils and Board, the Foundation has funded more than 450 individuals, many in the early years of their research careers. Most have been successful in obtaining federal funding to extend the work started
with ABMRF support. The presentation also highlighted the catalytic effect in bringing together scientists from many disciplines. By preserving the arms-length relationship between the funding source and the decisions regarding which individual applications were most worthwhile, ABMRF has provided important support to the alcohol research community.

Dr. Louise Nadeau, Professor at the Université de Montréal and Foundation Board member, moderated a session exploring work undertaken over 25 years by three “generations” of grantees focused on the behavioral responses to alcohol in social drinkers. Dr. Muriel Vogel-Sprott represented the first generation. She is professor at the University of Waterloo and began the session by describing the phenomenon of alcohol tolerance, explaining that her early observations that tolerance appeared dependent on the situation seemed to challenge the traditional view it was purely a physiological adaptation to the drug. She described her findings showing alcohol tolerance resembles a learned response that becomes dominant if associated with a reward, and subsides when the reward is withdrawn. Her work provided a compelling demonstration of how the expectation of some favorable outcome for the display of sober behavior can be a critical motivator in the development and maintenance of alcohol tolerance. Dr. Mark Fillmore began in the field under the direction of Dr. Vogel-Sprott and is now professor at the University of Kentucky. He described his work that focused on the kinds of behavioral effects from alcohol that drinkers expect. Individuals differ considerably in the type of effects that they expect from drinking and how these expectancies influence aspects of alcohol-related behavior, including the drinker’s patterns of alcohol use and the drinker’s actual response to alcohol. He showed how a drinker’s impairing response to alcohol can be reduced by providing information that alters the drinker’s expectancies about alcohol’s effects. The work has important implications in areas such as harm-reduction. Dr. Cecile Marczinski, assistant professor at the University of Kentucky who trained under Dr. Fillmore, opened her talk by saying none of the work described by her mentors would have been possible without the support provided by ABMRF because no government agencies in their time were funding the kind of innovative work they proposed. Her work focuses on how alcohol impairs specific mechanisms of behavioral control and which mechanisms can adapt or compensate for impairment, based on a cognitive behavioral control model that postulates that two distinct processes govern behavioral control: one that activates behavior and one that inhibits behavior. The work offers promising insights into understanding why binge drinkers are 14 times more likely to drive while impaired than non-binge drinkers.

The closing session explored drug development for alcohol use disorders, underscoring the long-term gains from funding basic research and it also demonstrated the tremendous talent of Board and Council members working at the forefront in bringing science into clinical practice. Dr. Ivan Diamond, Foundation Board member and Vice-President of Neuroscience for CV Therapeutics, offered insight into how drug development for a condition such as alcoholism proceeds from observations made in basic science. He was the founding Director of the Gallo Clinic and Research Center and was heavily engaged in pioneering work to understand the biochemical basis for AUD. In his current biotech industry role, he is leading a team to develop an effective drug to limit excessive alcohol consumption. Preliminary results suggest that a novel compound that reversibly inhibits aldehyde dehydrogenase may reduce consumption in an animal model of excessive drinking. Interestingly, this compound does not appear to influence alcohol consumption in “non-alcoholic” rats. His presentation outlined the value of basic science in drug development and promise for selectively reducing problems related to heavy consumption. Dr. Raymond Anton, Vice-Chair of the ABMRF Board and professor at the Medical University of South Carolina reviewed data from the recently published COMBINE Study sponsored by NIAAA. He was a lead investigator examining the efficacy of naltrexone, a currently available medication in alcoholism treatment used as a single agent or in combination with motivational or other psychosocial interventions. Most importantly, his presentation emphasized the need for large scale clinical trials to demonstrate efficacy of interventions, even when smaller, uncontrolled studies are highly suggestive. This principle of clinical investigation is likely to play a major role as more medications and other interventions are developed to treat alcohol use disorders.