like the red and green ivy cover the best [that was the Fall 1983 issue of DM—see "Turning Thirty" for it and other past covers].

2) After I left DMS, I earned an M.S.J. from Ohio University. For my thesis, I examined the coverage in the U.S. of the flu pandemic of 1918 and offered some ideas as to why an event of such magnitude didn't have a proportional impact on recorded history. So the article on that event was also very interesting to me. When I was writing about it in the late 1980s, there was still no clue as to the makeup of the virus involved.

I've enjoyed keeping up with the magazine for the last 20 years—it's an impressive periodical.

Steve Adams
Durham, N.H.

Adams, editor of the magazine from 1977 to 1986, is now the communications coordinator of the New Hampshire Sea Grant Program.

The whole picture
Dean Spielberg's essay on pharmacogenetics in the Fall 2006 issue ("On the cusp of change") opened a window into understanding and predicting individual differences in response to medications. Unfortunately, he allowed many other influences on the effects of drugs to take flight out the window—socio-behavioral factors that have been empirically validated for explaining individual variation in drug response but that lack the attraction of high-tech, bench science. The fact that these social and behavioral factors are less scientifically glamorous than pharmacogenetics does not make them any less important to practitioners and patients struggling to make the medicine fit the person.

Medication is never taken in a socio-environmental vacuum. Stress, as well as protective factors, influence the ways medications are ingested and metabolized and find their way to target organs, cells, and receptors. These include expectancies; adherence; nutrition; activity and exercise; concomitant use of alcohol, cigarettes, and illicit drugs; family relationships; the emotional climate in work and home settings; and the doctorpatient relationship. As stated by Dr. Antonia Novello in the same issue of Dartmouth Medicine, "Health-care professionals certainly have an obligation to advance the technology and science of medicine . . . but it is just as important to preserve the human element of medicine."

Robert P. Liberman, M.D.
DC '59; DMS '60
Lake Sherwood, Calif.

Be sure to tell us when you move! If your address changes and you want to keep getting Dartmouth Medicine, just tear off the address panel from the back of a recent issue, write your new address next to the old one, and mail it to: Dartmouth Medicine, 1 Medical Center Drive (HB 7070), Lebanon, NH 03756. It helps us greatly— since our mailing list is drawn from six separate databases—if you send the actual cover or a copy of it. If that's not possible, please include both your old and new addresses. Note, too, that if you receive more than one copy of the magazine, it's because of those six databases (which are in different formats, so they can't be automatically "de-duped"). We're happy to eliminate duplications, but it's a help to have the address panel on all the copies you get, not just the one(s) you'd like deleted.

Liberman is a Distinguished Professor of Psychiatry at the University of California-Los Angeles. We invited Dean Spielberg to respond to his observations, and he replied as follows: "I would like to thank Dr. Liberman for his thoughtful letter; it allows for the continued dialogue that no short, targeted article can achieve. He is truly correct that socio- behavioral factors have a huge impact on pharmacotherapy. The single largest reason for failure in effectiveness of a medicine is failure to take that medicine properly; many side effects result from the failure to take a medicine correctly (whether it be a matter of dose, with or without food, drug-drug interactions, etc.). The most important determinant of successful therapeutics is the therapeutic relationship between doctor and patient, the mutual teaching and learning that occur over time, and, indeed, the time spent working together to achieve optimum health and treatment of illness.

"The future of medicine depends on an integrative approach to the science and art of medicine—and it always has—but due to advances in scientific understanding, the nature of 'temporary facts' replaced by new insights is moving at an ever-greater pace. The old, and useless, arguments about 'nature versus nurture' need to be replaced by an integrated view of human biology and life. We think and feel using chemicals in our brains; our experiences modify that

chemistry (not to speak of neuroanatomy and physiology) and future responses, and medicines also modify chemistry as well as behavior. Yet the impact of both life experiences and of medicines is modified by genetic background. The likelihood of developing depression has been related both to genetic differences (for example, in serotonin reuptake mechanisms) and to 'traumatic events' in life; the interaction of genes and environment is particularly striking in this case.

"What perhaps has not been as well explored in an integrated manner from these data is the implication that both medicines and 'environmental modification' (behavioral and other) also will likely impact outcomes. The impact of both medicines and behavioral modification is, in turn, likely to be modified by genetic background. If doctors are to truly benefit patients, we need to be able to integrate the 'heart and head' of medicine. I hope that Dartmouth Medical School is preparing our students for just such a lifelong journey. May the dialogue continue."

Tuskegee redux
An article in your Fall 2006 issue ("Genetic testing may reveal a quagmire of complex questions") referred to "research scandals such as the federally funded Tuskegee study, in which poor black males were denied effective treatment in order to study the natural history of syphilis."

Let me try to set the record straight. In the 1920s, Brusgaard published a classic study on the fate, after many years, of patients who contracted syphilis but were never treated. He found that a third were seronegative, a third were seropositive but otherwise well, and a third had active tertiary syphilis—usually with central nervous system (CNS) or skin involvement.

The Tuskegee study was instituted because it was not known what the outcome of the disease would be in seropositive black men, who have a high incidence of cardiovascular complications from tertiary syphilis. Remember, at the time syphilis was endemic in the rural South.

When penicillin was introduced widely in 1946-47, it was soon learned that the rapid killing of the syphilis spirochete, especially in patients with tertiary disease, frequently resulted in a severe Herxheimer reaction and possible death.

During 1946-47, I was a corpsman in the U.S. Navy and observed this reaction frequently. Most of the patients I saw were white men with CNS involvement.