1. You were a medic taking on a career in alcohol research. Was that usual at the time? Were there many psychiatrists going into research?
I was constantly amused, but never felt threatened at how some physicians outside the alcohol field seemed to look down on this line of work as a badway to spend time. However, as I looked around, I saw some awesome people who were studying alcoholism. I could hardly think of a more important public health problem, and I thought, my goodness, what are you other docs missing? Alcohol is a fascinating field.
2. How was your introduction to alcohol issues?
My interest in alcohol problems really began when, as a first-year medical student, I got a job with Lee Robins* at Washington University. Until then I had no idea I was interested in alcohol and no idea that I was going to go into research. So I was lucky in my first year of medical school, 1964, to find a job posted on a bulletin board for someone to help in a study interviewing men for a follow-up project. That was my introduction to Lee Robins, a woman who became an important part of my life. She taught me how to ask a question and how to gather data to try to address the question. It was further luck that the question she was addressing at the time had something to do with alcohol.
3. I have been privileged to look at your list of publications. There are about 600 of them. You have probably published about 20 research papers each year of your professional life. It is difficult to read one’s way beyond the detail and discern the deeper story. Can you help?
I have been fortunate to have had consistent funding for my own research from the National Institute of Alcoholism and Alcohol Abuse (NIAAA) over the years. Also, I have been associated with groups of people who have been very productive, such as the Collaborative Study on Genetics of Alcoholism. So there are papers directly from my own laboratory and others that I contributed to, but with someone else as senior author. My research has followed a series of issues over the years. First came the question of whether alcoholism is a psychiatric disorder, a medical condition or a manifestation of pre-existing psychiatric disorders, as many people believed. So my early work related to trying to learn more about the natural history and the relationship of severe and repetitive alcohol problems to major psychiatric disorders.My research has followed a series of issues over the years. First came the question of whether alcoholism is a psychiatric disorder, a medical condition or a manifestation of pre-existing psychiatric disorders, as many people believed. So my early work related to trying to learn more about the natural history and the relationship of severe and repetitive alcohol problems to major psychiatric disorders. The second phase started after I became convinced that alcoholism is a condition that is distinct from other psychiatric disorders, not just a variation of pre-existing conditions. Next came the question of what causes it. Science might never answer that question in its entirety, but the beauty of research is that it gives you the opportunity to ask a series of questions, contributing to a body of knowledge where you are only a small part of a fascinating larger question. The second phase started after I became convinced that alcoholism is a condition that is distinct from other psychiatric disorders, not just a variation of pre-existing conditions. Next came the question of what causes it. Science might never answer that question in its entirety, but the beauty of research is that it gives you the opportunity to ask a series of questions, contributing to a body of knowledge where you are only a small part of a fascinating larger question.
4. Beyond that?
The next phase asked how might the genetic factors operate to affect the risk for heavy drinking and alcohol problems.To me, one important breakthrough came from T.-K. Li, Jean Pierre vonWartburg and others, who identified changes in genes that affect alcohol metabolism, especially in Asians, and were protective from alcoholism. So, at the time in the 1960s when I was beginning to become interested in this problem, it was obvious that variations in genes for aldehyde dehydrogenase contributed, at least in Asians, to whether someone is more or less vulnerable to this disorder. So I started to say, OK, one possible mechanism is protective, perhaps I could help to study other mechanisms that relate to the vulnerability for alcoholism. For that, I was impressed by papers published in the 1960s and 1970s that described early-onset alcoholism in the context of antisocial behavior.
Because such impulsivity ran in families and contributed to a wide range of problematic behaviours, it seemed to indicate a second, potentially genetically influenced, characteristic that might impact on the alcoholism risk. Evidence for this idea had been there since at least the 1940s. Regarding the next phase of my work, asking what is it that might be inherited, there was already evidence for one protective factor and a different vulnerability factor that increased the risk for both alcoholism and drug dependence.
The next phase came from the fact that I am a clinician. I started to ask my patients to tell me about how alcohol initially affected them early in their drinking careers. Most of them said, ‘Early on I could drink everyone under the table’. Many said, ‘I would be the designated driver even though I was drinking twice as much as other people’. Those answers surprised me and got me to the current phase of my work. We conducted evaluations of 18–25-year-old children of alcoholics and controls, matched on demography and drinking history, which showed that young subjects with alcoholic relatives had a lower level of response to alcohol . A 10-year follow-up of 99% of these subjects, combined with additional work, revealed that the low level of response predicts later alcohol dependence , and that this low response was familial, biologically based and potentially genetically influenced [6–8]. We also conducted a series of studies searching for genes contributing to the low alcohol response [9,10] and developed models that identified some environmental factors mediating the impact of a low response on alcohol outcomes [11,12]. Our current efforts are beginning to use the mediators and genetic results to develop preventative trials to diminish the alcoholism risk in adolescents with low alcohol responses.
6. Before we close I want to ask you about the DSM system, because you have played an important role in its development. Where do you want to see it going now?
My bias is that our approach to diagnostic criteria for major psychiatric disorders is, in some ways, the equivalent of bright but somewhat blind people feeling an elephant. Currently, we do not fully understand the disorders we work with and no one view generated from a particular vantage point is necessarily more accurate. Since 1980 (DSM-III), we have looked increasingly to data to help with our decisions, and that is a good thing. However, we may not have enough new information yet to justify major changes from DSM-III-R and DSM-IV to DSM-V. I fear that if we are not careful, we could change the names and shuffle the criteria, so there might be different blind people feeling the elephant, but now from the front rather than from the back. However, I am not so sure we need a radically different DSM-V now. The new diagnostic manual is being put together and I am participating, but I want to be sure that if we are going to do it, it be done in a way that is doing the most good with the least harm.