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Meet Clive Harper, M.D., FRCPA

Clive HarperWinner of the Begleiter Research Award at the 2009 annual meeting of the Research Society of Alcoholism held in San Diego. Writer Sherry Wasilow interviewed Dr. Harper via e-mail while he was en route from Oman to his home country of Australia for this profile.

SW: What has been your research focus?

CH: My colleagues and I have established a “brain bank.” We have gathered a wide cross-section of the population – that is, people who have brain disorders as well as people without disorders (controls). In 2002, we started a brain donor program called “Using our Brains”. People commit to donate their brains to medical research after they die, in much the same way as you might commit to donate your organs for transplantation. Consented donors have repeat neuropsychological assessments throughout their life with health, lifestyle, and clinical work ups. The detailed profiles that result from this program are extremely useful for researchers using the New South Wales Tissue Resource Center (TRC) tissues. This brain bank is an important resource that will become even more valuable as new techniques are developed for the study of neuropsychiatric diseases. The TRC encourages neuroscience research, particularly into alcohol-related brain damage.

SW: How did you arrive at this research focus?

CH: I first became interested in alcohol research when I worked in Glasgow University and the Southern General Hospital, in Scotland, in 1972. I had finished my medical degree and postgraduate training in pathology in Australia and had just begun to train as a neuropathologist. As many readers may already know, a neuropathologist specializes in the study of disease of the brain and spends most of his/her time studying brains from autopsies or looking down a microscope at samples of brains taken and processed in a laboratory. Part of my job in Scotland involved the study of the brains of people who had become Coroner or Medical Examiner’s cases.

I was astounded by the number of cases that we saw that had severe, permanent brain damage caused by, what was presumed to be, thiamine (vitamin B1) deficiency. This disease is known as the Wernicke Korsakoff Syndrome (WKS). When I returned to Australia, I took up the position of neuropathologist in Perth, Western Australia and was again involved in the study of the brains of thousands of cases each year from the Coroner’s office and public hospitals. There were even more cases of chronic brain damage caused by thiamine deficiency in Australia. We published these data in peer-reviewed articles in national and international journals; thus began my research career. I had made a scientific observation about the apparent high prevalence of a particular disease in Scotland, taken this knowledge back to Australia, and made the same surprising observation. WKS was even more common in Australia than in Scotland. Why was this so? The critical issue that we identified was that more than 90 percent of the Australian cases were associated with alcohol abuse.

Subsequently, my colleagues and I reviewed all of the hospital files of these cases and were able to show that the diagnosis of approximately 80 percent of the WKS cases had been missed or overlooked in major teaching hospitals. Although the standard textbooks of the day indicated a particular pattern of clinical signs for WKS, we showed that these were rarely all present in our cases. We suggested that clinicians needed to be very alert to make the diagnosis of WKS and that, if cases were admitted where there was a history of alcohol use/abuse, they should be treated with thiamine “just in case.” It could do no harm and thiamine supplements have been shown to quickly reverse the clinical signs and symptoms of WKS and reduce the brain damage. There are still many people each day developing this type of preventable brain damage (WKS), particularly in countries where alcohol use/abuse is becoming more common, and clinicians still need to be alert and consider the possibility of this diagnosis.

These prevalence studies provided the main impetus for 1991 Australian legislation that mandated thiamine supplementation of foodstuffs (bread flour). This has led to a dramatic reduction in the prevalence of WKS in Australia. It is, however, important to realize that the research is just the beginning. Translation of research outcomes to clinical practice and effective public-health measures is probably more difficult than the original research. One must be prepared to debate with health-care professionals and politicians to achieve these goals. I feel that this has been one of my major career achievements. We were able to take our research out of the pathology laboratory and into the clinic and public-health arena.

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