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HarvardMedicine SPRING 2010

the science & the art of healing

Savoring

the

5 Senses

Harvard doctors explore the depths of our perception


SPRING 2010

VOLUME 83

32

NUMBER 1

Special Report

Contents

BEYOND THE FIVE SENSES

10 Sight Amazing Grace A man loses his sight—and finds himself. by Elissa Ely Vision Research Buffet

18 Hearing

The Sounds of Silence A psychiatrist explores the richness of communicating without voice. by Sanjay Gulati Auditory Research Buffet

10

26 Smell

Catching the Bouquet What can wine connoisseurship teach doctors about diagnosis? by Michael A. LaCombe Olfactory Research Buffet

32 Taste There’s No Accounting for Taste Is picky eating simply in poor taste? by Perri Klass Gustatory Research Buffet

38 Touch The Man in the Mirror What can phantom sensations teach us about how our brains talk to our bodies? by Atul Gawande Somatosensory Research Buffet

44 Beyond the Five Senses

 Aristotle missed the mark. by Alice Flaherty

50 The Sixth Sense

She was clinically dead, but she still heard— and remembered—the surgical team’s words. by Allan J. Hamilton 

Departments 2 From the Dean 3 Letters to the Editor

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4 Pulse

Harvard in Haiti, health care reform, a new executive dean for research, and a new approach to brainstorming new research approaches

7 Benchmarks

Predicting strokes, treating trauma, mapping cancer, understanding sudden infant death syndrome, and weighing in on aspirin

52 Assembly

Instructions

How to Build a Better Doctor

54 Smart Science Harvard doctors design smart clothing with all the right accessories to diagnose, monitor, and treat patients with a range of conditions

56 Five Questions The Coming Revolution: Five Questions on Neuroscience for Michael Greenberg

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HarvardMedicine

From the Dean

THOUGHTS ON INNOVATION

Letters to the Editor

Editor Paula Brewer Byron Associate Editor Ann Marie Menting

SECOND OPINIONS FROM OUR READERS

Assistant Editor Jessica Cerretani Editorial Interns Erin Long, Molly Marcot

The last time this magazine was redesigned, more than a decade ago, the editor felt justified trepidation. The late Francis Moore ’39, a giant in the surgical field and the commanding mentor of generations of Harvard surgical residents, was monitoring her plans closely. He warned her against making drastic changes. The Harvard Medical Alumni Bulletin was sacrosanct, he told her, and must be treated reverently. “The Bulletin,” he explained, with sonorous emphasis, “is like Shakespeare and the Bible.” He ended up applauding the redesign but cautioned the editor: “Don’t let your designer go wild.” While the editor and designer have remained the same, this issue of the magazine bears not

Contributing Writers David Cameron, Elizabeth Dougherty, Karin Kiewra, Alyssa Kneller, Emily Lieberman, Veronica Meade-Kelly, Carol Cruzan Morton

Editorial Board JudyAnn Bigby ’78; Emery Brown ’87; Rafael Campo ’92; Michael Chernew, PhD; Nicholas Christakis ’88; Elissa Ely ’88; Paul Farmer ’90; Daniel D. Federman ’53; Timothy G. Ferris ’92; Alice Flaherty ’94; Atul Gawande ’94, Robert M. Goldwyn ’56; Jerome Groopman, MD; John Halamka, MD; Donald Ingber, MD, PhD; Sachin H. Jain ’06; Perri Klass ’86; Jeffrey Macklis ’84; Victoria McEvoy ’75; Barbara McNeil ’66; Lee Nadler ’73; James J. O’Connell ’82; Nancy E. Oriol ’79; Anthony S. Patton ’58; Mitchell T. Rabkin ’55; Eleanor Shore ’55; Rachel Wilson, PhD Dean Jeffrey S. Flier, MD

that some of our readers have been receiving this magazine for more than seven decades. That’s

Executive Dean for Administration Daniel G. Ennis, MBA, MPA

quickly learns. But at Harvard Medical School we’re trying to improve on many wonderful, solid foundations. This issue looks beyond the five senses—an improvement on the Aristotelian tradition of vision, hearing, smell, taste, and touch. Throughout its pages you’ll find inextricable links between the senses: the feeling of sound, the drawing of objects by feeling them rather than seeing them, [third example]. And you’ll find an examination of how the five senses fail to capture our full sensory experience. The success of the new chapter of this magazine’s history will rely on your feedback. We encourage you to join our Readers’ Panel—which allows you to receive all magazine surveys, requests for ideas, and easy communication with our expanded Editorial Board. One of our Editorial Board members described our plan for redesigning the magazine “Bulletin plus”— and that’s what we hope it will prove to be.

[need signature] Jeffrey S. Flier Dean, Harvard Medical School

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Associate Dean for Communications and External Relations Gina Vild Harvard Medical Alumni Association Steven E. Weinberger ’73, president Gilbert S. Omenn ’65, president-elect 1 Phyllis I. Gardner ’76, president-elect 2 Kenneth Offit ’81, vice president Neil R. Powe ’80, secretary Deborah C. German ’76, treasurer H. Thomas Aretz ’76; JudyAnn Bigby ’78; Rosa M. Crum ’85; Laurie Glimcher ’76; Elizabeth Petri Henske ’85; Katherine Janeway ’00; Jim Yong Kim ’86; Triste N. Lieteau ’98; Eileen Reynolds ’90; Michael Rosenblatt ’73; David H. Sachs ’68 Rahul Sakhuja ’03 Chair of Alumni Relations A. W. Karchmer ’64 Harvard Medicine, formerly known as the Harvard Medical Alumni Bulletin, is published three times a year at 25 Shattuck Street, Boston, MA 02115 Publishers: Harvard Medical School and Harvard Medical Alumni Association © President and Fellows of Harvard University Phone: 617-432-7878 • Fax: 617-432-0089 Email: harvardmedicine@hms.harvard.edu Web: http://magazine.med.harvard.edu Third class postage paid at Boston, Massachusetts. Postmaster, send form 3579 to 25 Shattuck Street, Boston, MA 02115 ISSN 2152-9957 • Printed in the U.S.A.

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charles hartness ’82 portland, oregon

Magical Mystery Cure Your article on medical mysteries in the Autumn 2009 issue brought to mind a curious case I encountered early in my career. In the early 1960s, a family brought their five-year-old daughter to my new practice in Maine. Her staggering gait and slurred speech alarmed me. Thinking it might be a brainstem tumor, I referred her to Children’s Hospital in Boston, where I had recently completed my training. There, the neurologist and residents checked her over as best they could in the days before MRIs. She gradually improved and they eventually discharged her, assuming that she had suffered some sort of transient cerebellitis. Several weeks later she was back in my office with the same symptoms. After reviewing the thorough family and social history I had taken (in proper Harvard fashion), it occurred to me that an aunt who lived with the family might be taking Dilantin for her epilepsy; an overdose of the drug could certainly cause the girl’s

symptoms. My simple suggestion to the family produced another recovery and prevented other recurrences. charles e. burden ‘59 augusta, maine

A Whiter Shade of Pale The introduction in the “Skeletons in the Closet” issue caught my eye, especially the mention of how John Collins Warren’s bones had been “carefully preserved” and “whitened” according to his own instructions. While studying for an anatomy exam at Dartmouth Medical School in 1951, before I transferred to HMS, I spent an afternoon in a darkened museum surrounded by specimen cabinets. In one cabinet I found a strikingly white, porcelain-light skull with hinged trapdoors that opened to labeled cranial nerves and foramina. Arteries and veins had been removed, and their paths along the skull’s inner surface had been diagramed in red and blue. I later revisited the skull and

found a trapdoor I had overlooked. Beneath it was inscribed “Prepared by Oliver Wendell Holmes—1840.” Holmes, HMS Class of 1836, had been an anatomy professor at Dartmouth for two years before returning to Harvard in 1840. I have been teaching anatomy at the Florida State University College of Medicine since retiring from general surgery in 1997. I have seen many skull preparations but none as exquisite as that one. Holmes’s whitening process was special; a demineralization likely explained the lightness. Unfortunately, the skull can no longer be found. There is a good chance, though, that a similar trapdoor skull that Holmes produced is in a specimen cabinet at Harvard. Such a skull would be a welcome addition to the School’s Warren Anatomical Museum. Meanwhile, I suspect that Holmes helped orchestrate the whitening of Warren’s bones. james cavanagh ’54 tallahassee, florida

A Pressured Gage The Autumn 2009 Bulletin brought back memories from 50 years ago, when I was based at the Warren Anatomical Museum, where Phineas Gage’s skull and tamping iron were on display. The trajectory of the wound suggested injury to the left frontal lobe and perhaps to the medial aspect of the right frontal lobe. After his accident, Gage was reported to have experienced changes to his personality but not to his language function. The newly discovered photograph of Gage shows him holding his tamping rod as would a left-handed baseball batter—at the left shoulder, left hand on top—and with his hair parted on the right in the style of a lefthanded man of that era. He may have adopted his hairstyle after his injury, of course, to conceal his cranial defect. If, as the photograph suggests, Gage was right-cerebral dominant, that would better help explain his personality change and his intact language function. simeon locke, md boxford, massachusetts

harvard medicine ~ spring 2010 3


CAPTION: to come to come to come to come to come

PULSE

“Insurance is the most administrative, costly, financially distortive form of financing that exists.This is why, outside of health care, insurance is only used for things that are rare, unpredicatable, and major.

MAKING THE ROUNDS AT HMS AND BEYOND

CAPTION: to come to come to come to come to come

HARVARD IN HAITI

More than 500 doctors and nurses have pitched in to help

o

n January 12, the ground began to shift under Louise Ivers. The HMS assistant professor of medicine and clinical director in Haiti for Partners in Health was in Portau-Prince discussing, ironically, disaster preparedness when a 7.0-magnitude earthquake struck. Dazed, Ivers watched nearby buildings collapse around her. As she picked herself up off the floor, she was snapped from her trance with a bystander’s six simple words: “I wish someone was a doctor.” Within days, she was attending to acute injuries in the local hospital. Stories such as this illustrate

4 harvard medicine ~ spring 2010

the “living links between Harvard and Haiti,” says Paul Farmer ’90, cofounder of Partners In Health (PIH). Such a relationship has long existed between PIH and the impoverished country. The nonprofit organization has been working in Haiti for more than 20 years to help prevent and treat such diseases as AIDS and multidrug-resistant tuberculosis. When the quake hit, PIH—with its existing network of health services and workers—became a chief international resource for coordinating the emergency response. Although the group’s own facilities were largely

untouched by the disaster, other medical institutions weren’t so lucky: A nursing school—one of only three in the country—was destroyed, killing some 150 students. Losses like this reinforce the need for international aid, says HMS Dean Jeffrey Flier. Much of that help has come from the Harvard community, with roughly 500 medical professionals offering assistance. The Harvard Humanitarian Initiative has coordinated a group of medical, surgical, and public health volunteers within Partners HealthCare System who have deployed to Haiti.

Massachusetts General Hospital and Brigham and Women’s Hospital have sent similar teams. Back at home, the University has established the Harvard Haiti Emergency Relief Fund for Employees, which uses donations from the Harvard community to provide financial assistance to the nearly 100 employees with direct ties to Haiti and their families. Meanwhile, PIH has expanded its focus to include not only immediate medical assistance for those affected by the quake, but also long-term recovery and rebuilding initiatives. To that end, PIH has created the Stand with Haiti Fund, aimed at supporting a strategy for improving the country’s public health system. “Haiti needs to be built back better and stronger than before,” says Farmer, who stresses the importance for Harvard to continue to play a key role in that process. “A university like ours,” he adds, “can offer its own brand of pragmatic solidarity and set the highest standards for research, teaching, and service.”

TO READ MORE ABOUT HAITI website information goes here website information goes here website information goes here website information goes here website information goes here website information goes here website information goes here website information goes here website information goes here website information goes here

HEALTHY DEBATE

A panel of experts wrangled with health care reform

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or those who enjoy political theater, the national health care debate has not disappointed. But good theater and cogent debate rarely coexist. To add a measure of thoughtful discussion to the mix, HMS Dean Jeffrey Flier invited a group of experts to debate the subject at the School in January. The presenters, with one exception, were not hopeful about the prospects of meaningful reform, citing everything from a flawed funding structure to a dysfunctional political process. According to Allan Detsky, professor of health care policy at the University of Toronto, governmental structure is the main problem facing health care reform in the United States. He contended that it is far easier to approve legislation under a

parliamentary system in which the executive and legislative branches are “always together” when there is a majority government. David Goldhill, author of a recent article in The Atlantic, which indicts the nation’s health care system, began exploring the health care industry in depth after his elderly father died from a hospital-acquired infection. He views the recent bill as simply expanding a broken system focused on coverage, not care. “Insurance is a form of finance,” he explained. “It is the most administrative, costly, financially distortive form of financing that exists,” he said. “This is why, outside of health care, insurance is only used for things that are rare, unpredictable, and major. In health care we use insurance for

everything.” Goldhill’s recommendations for reform include establishing a national catastrophic policy that would require people to save for their health care and pay for part of it, and drawing consumers back into the system. David Cutler, a Harvard University professor of economics who was senior health care adviser to Barack Obama’s presidential campaign, expressed cautious optimism. The answer to inefficiency and waste in the health care system is to target the supply side, which is more precise and effective than targeting the demand side, he said. Data show that hospital admissions drop when hospitals receive incentives not to keep patients for long periods. But if you target the demand side with price incentives, Cutler

explained, patients will often not act in their best interests and may switch to cheaper and less effective medications and therapies. The current plans, which include some supply-side incentives, represent “a path, not a leap,” he cautioned. “Passing the legislation is only 15 percent of the challenge. The remaining 85 percent is making it work.” Daniel Kessler, the final speaker, disagreed almost entirely with Cutler. A professor of management at Stanford University, Kessler claimed that the proposals would cause fiscal problems and that health insurance does not necessarily improve health. The plans, he contended, would create another middle-class entitlement program, massive work disincentives by generating an implicit marginal tax rate, and openings for increased government involvement in people’s private lives. Kessler conceded, however, that he could

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harvard medicine ~ spring 2010 5


BENCHMARKS

BACK TO SCHOOL

Chin will lead the effort to find new ways to translate research

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his May, one of Harvard Medical School’s notable graduates will return to the fold. After a decade-long stint at Eli Lilly and Company, where he served most recently as president for discovery research and clinical investigation, William Chin ’72 will rejoin the HMS community in a full-time capacity. The molecular endocrinologist was recently named HMS executive dean for research, a newly created position with overarching responsibility for biomedical investigations at the School. In this role, Chin will spearhead efforts to design and implement a vision for research at HMS, focusing specifically on interdisciplinary investigations that cross departmental and institutional boundaries. He will also hold an academic appointment as an HMS professor of medicine. Chin has had a longstanding relationship with his alma mater and its affiliates. After training at Beth Israel Hospital and Massachusetts General Hospital, he served on the faculty in the Department of Medicine at Brigham and Women’s Hospital. He later became chief of the Genetics Division at that hospital, as well as a Howard Hughes Medical Institute investigator

and a professor of medicine and of obstetrics, gynecology, and reproductive biology at HMS. Chin has published nearly 300 papers, chapters, and books and received numerous awards for his research and mentorship. Many of Chin’s investigations have embraced the concept of translational research, connecting basic scientific discoveries to their relevance in animals and humans. This approach makes Chin a fitting choice to develop and guide new research initiatives. “One of Bill’s highest priorities,” says HMS Dean Jeffrey Flier, “will be to help find new ways to transform the world’s most vital biomedical research into therapies that can directly improve human health.” At a time when industry ties to research are in the spotlight, Chin’s past experience at Lilly is also a benefit: He will develop a coherent strategy for the School’s scientific interaction with industry, ensuring it is aligned with the HMS Faculty Policy on Conflicts of Interest and Commitment. “There are very few people capable of rising to meet such challenges,” says Flier. “I’m thrilled that Bill will be joining the HMS leadership team.”

“One of Bill’s highest priorities will be to help find new ways to transform the world’s most vital biomedical research into therapies that can directly improve human health.” —Jeffrey Flier

WILLIAM CHIN

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DISCOVERY AND INNOVATION AT HMS

Tricks of the Light

For spiritualists, auras can provide luminous insight, but for those who suffer migraines, auras can have sinister connotations. Nearly 20 percent of the population suffers migraines, with one-third of them experiencing pre-migraine auras. Past studies have linked the risk for vascular ischemic events to migraines with aura. But a study of more than 27,000 women in the January issue of Headache found more nuanced associations. Led by Markus Schürks, an instructor of medicine at Brigham and Women’s Hospital, researchers found a doubled risk for cardiovascular disease, myocardial infarction, and ischemic stroke among women who experience migraines with auras compared with those whose migraines are aura-free. The link with ischemic stroke, however, was actually stronger when there were no migraine features, such as aura, nausea, and sensitivity to sound or light.

Thought that Counts

Got a bright idea? Harvard Catalyst, the Harvard Clinical and Translational Science Center, wants to know. Using federal stimulus funding from the National Institutes of Health, the group has joined with InnoCentive, a global platform for innovation contests, to launch a series of challenges aimed at uncovering novel solutions to thorny scientific problems. Such contests, which have been used to foster innovation in the business sector, may spark investigations in medicine, as well. The first contest, which concluded in March, challenged the entire Harvard community—including faculty, students, administrators, and staff—to brainstorm fresh ideas related to type-1 diabetes. This condition “has touched many people at Harvard and elsewhere,” says Dana-Farber Cancer Institute’s Eva Guinan, one of the project’s leaders. “As a result, they may have questions or ideas that could help spawn new collaborations and areas for research.” To sweeten the deal, Harvard Catalyst is offering between $2,500 and $10,000 in prize money to people who submit the ideas a review panel deems most innovative. For more information on this and future contests, visit www.innocentive. com/HarvardCatalyst.

BRAIN STORM WARNINGS

A new forecast for early stroke recurrence goes by the numbers

a

Web-based tool developed at Massachusetts General Hospital may provide a much-needed 90-day forecast on the risk for a second stroke among people who have suffered one such calamity. A stroke soon after an initial one

increases the chance of death or severe disability, writes Hakan Ay, an HMS assistant professor of radiology, in his January 12 article in Neurology. The tool—the recurrence risk estimator at 90 days—scores risk by assessing data such as age, type of first stroke, and

brain scans. The higher the score, the greater the likelihood of a repeat attack. The study also showed that long-term stroke predictors—smoking, diabetes, and hypertension— are not predictive of short-term recurrences.

Anorexics have been found to have excess fat—in their bone marrow. * www.magazine.hms.harvard.edu

harvard medicine ~ spring 2010 7


THE INSULTS OF INJURY Mitochondria may

be at the root of dangerous complications stemming from trauma

i

nflammation is at the root of most serious complications occurring after both infection and injury. But while the molecular course of events that leads from microbial infections to the inflammatory condition called sepsis is fairly well understood, it is far less clear how and why physical injury can result in a similarly dangerous inflammatory response. Now a study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) suggests that mitochondria—the body’s cellular “power plants”—are released into the bloodstream following physical injury. And because mitochondria closely resemble the bacteria from which they originated, they appear to elicit a sepsis-like immune response, changing from a vital source of cellular injury to a dangerous “enemy within.” Appearing in the March 4 issue of Nature, the findings could eventually lead to new strategies in the management of trauma as well as to the development of new tests to help clinicians discriminate between infective and non-infective

Untangling Clues

Researchers at Children’s Hospital Boston have linked sudden infant death syndrome (SIDS) with low production of serotonin in the brainstem, based on a comparison of brainstem samples from infants dying of SIDS compared to brainstems of infants dying from other, known causes. The findings, published in the February 3 issue of The Journal of the American Medical Association, may give a concrete approach to identifying babies at risk for SIDS, the leading cause of death for infants in the United States. In the brainstem, serotonin helps regulate some of the body’s involuntary actions, such as breathing, heart rate and blood pressure during

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inflammation. “The body’s vital organs can become dysfunctional when traumatic injury triggers the Systemic Inflammatory Response Syndrome, or SIRS,” explains senior author Carl Hauser, an HMS visiting professor of surgery at BIDMC. “Trauma kills 5 to 10 million people worldwide per year and among U.S. individuals under age 35, trauma accounts for more deaths than all other illnesses combined. Inflammatory complications are directly responsible for about one-third of those deaths.” Hauser, whose laboratory studies focus on neutrophils, circulating white blood cells that can attack the body’s organs, wanted to find out how neutrophils might be participating in this dangerous inflammatory cascade. The mechanisms that underlie both SIRS and sepsis are rooted in the body’s “innate immune” response. Unlike “acquired immunity,” which develops over time, innate immunity is present from birth, ready to immediately respond whenever immune cells encounter molecular patterns typical of external pathogens such

Mapping Cancer

An international team of researchers has created a genome-scale map of 26 cancers, revealing more than 100 genomic sites where DNA from tumors is either missing or abnormally duplicated compared to normal tissues. The study, the largest of its kind, finds that most of these genetic abnormalities are not unique to one form of cancer, but are shared across multiple cancers. “Our findings show that many genome alterations are universal across different cancers. Although this has been known for some types of changes, the degree to which so many alterations are shared was pretty surprising to us,” says senior author Matthew Meyerson, a HMS professor of pathology at the Dana-Farber Cancer Institute. “It suggests that, in the future, a driving force behind cancer treatment will be common genomic alterations, rather than the tumors’ tissue of origin.” The work appears in the February 18 issue of Nature. “These data signify an important resource for cancer gene discovery, but they’re only a first step,” says Meyerson. “With the ongoing revolution in genome technology, it will become possible to decode the genomes of thousands of cancers to reveal every genomic change.”

“Our findings suggest that, in the future, a driving force behind cancer treatment will be common genomic alterations, rather than the tumors’ tissue of origin.”

Facebook Doctoring

A Web-based tool developed at Massachusetts General Hospital may provide a much-needed 90-day forecast on the risk for a second stroke among people who have suffered one such calamity. A stroke soon after an initial one increases the chance of death or severe disability, writes Hakan Ay, an HMS assistant professor of radiology, in his January 12 article in Neurology. The tool—the recurrence risk estimator at 90 days— scores risk by assessing data

Aspirin and Hearing MICHELLE HOLMES

ONE A DAY

Regular use of aspirin-like compounds have been found to halve the risk for breast cancer recurrence or death

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he “take an aspirin” part stays intact, but there’s no need to call in the morning, at least not for women interested in the benefits found in research from Brigham and Women’s Hospital. According to data gathered from more than four thousand women who had received diagnoses of breast cancer, those who took aspirin and other nonsteroidal anti-inflammatory drugs had a significantly reduced risk of either dying from the disease or experiencing a recurrence. The study, published in the February 16 issue of the Journal of Clinical Oncology, also suggested that the protective effect was associated with the number of days per week that the women took the agents, with more days equaling lower risk. The study used data collected from more than 4,000 female nurses who had enrolled in hospital’s landmark Nurses’ Health Study and had been diagnosed with Stages I, II, or III breast cancer between 1976 and 2002. By analyzing selfreports from these women about their frequency

of aspirin use one year after their first diagnosis of breast cancer through June 2006 or their death, whichever came first, and then adjusting for stage of cancer, menopausal status, body mass index, and cancer treatments, the investigators found a 50 percent lower chance of death and a 50 percent lower risk of recurrence among those who took the drug. Women in the study reported taking the agents between 1 and 7 days each week, with improved risk found with 2 to 5 days of aspirin and 6 to 7 days of other NSAIDs. “More than 2 million women in the United States live with breast cancer and their risk of death from this disease is elevated even up to 15 years after diagnosis,” says Michelle Holmes, an HMS associate professor of medicine at the Channing Laboratory at Brigham and Women’s Hospital and lead author on the study. “More research is needed to determine how aspirin and other nonsteroidal anti-inflammatory drugs may work to prohibit the recurrence of this disease.”

If the man in your life doesn’t respond to your request to pass the pepper, his deaf ear may not be bad form. It might be the painkiller he takes. According to research led by Sharon Curhan, an HMS instructor in medicine at Brigham and Women’s Hospital, men under the age of 50 who took over-the-counter painkillers containing acetaminophen or aspirin or other nonsteriodal anti-inflammatory drugs increase their risk for hearing loss. Curhan found that 40-something men who took two or more doses each week of acetaminophen doubled their risk for hearing loss. Similar doses of aspirin raised risk more than 30 percent while for other NSAIDs, the risk increased 61

Delaying radiation after breast cancer surgery increases recurrence risk in older women. * www.magazine.hms.harvard.edu

harvard medicine ~ spring 2010 9


the

race

A man lets his eyesight fail, then his blindness reopens a lost world ~ by elissa ely

Our patient should not have gone blind. His glaucoma was treatable. When drops stopped working in one eye, a shunt was placed. When it failed, he believed it was an act of sabotage and that his ophthalmologist wished for him to go blind. It was a variant of the same voodoo that he felt had been cast upon him for years and that had caused hospitalizations since adolescence. His ophthalmologist wished nothing but sight for him, of course. My patient was offered other ophthalmologists, other clinics. But he was firm. There would be no further shunts, or any other treatment, by her or anyone else, in either eye. His decision was absolute. He preferred to lose his vision; that much was under his control. Large amounts of the many antipsychotic

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harvard medicine ~ spring 2010 2

senses: vision

5

g

Amazing


h

is monosyllables became lucid, animated monologues. It turned out he had read voraciously through his childhood and into the beginning of his psychiatric illness.

medications he had taken for years were not able to persuade him otherwise. His medical guardian was horrified. We were, too. This decision was based on delusion; the consequences would be irreversible. Surely treatment could be forced. Many conversations were held with the patient, and consultations were sought from eye doctors and forensic psychiatrists. In the end, though, no surgeon would bind him to a table against his will and operate. We watched while he slowly lost the sight that was savable. It was like the opposite of timelapse photography—in very slow motion, his view disappeared. Once a month, he still came to the clinic for his psychiatry appointment, listing along the hall, bumping into doors. The staff in his group home tried to teach him to master a collapsible white cane and enrolled him in a Day Program for the Blind, which budget cuts promptly closed. He would not have stayed there, though. He knew the place was full of rapists. In the clinic, he had always presented himself as a quiet,

stunted man with few interests (including himself): no friends, hobbies, habits. Under the circumstances, this was sensible. Anyone hounded by hallucinations and marked as the target of voodoo would find it hard to have a lively interest in the outer world. He was all monosyllables in meetings, and we assumed his private life was as vacant as his public one. But we were wrong. When he could no longer see outside of himself, he began looking inward. Caution is necessary here—the vision metaphor is cheap—but he seemed to be looking back at himself. After he went blind, for the first time he started to talk, not about voodoo and witchcraft. He was talking about books. His monosyllables became lucid, animated monologues. It turned out he had read voraciously through his childhood and into the beginning of his psychiatric illness. Books had raised him. Holding his collapsed cane, he sat in the office and recalled his literary life. He wanted us to know it. His reading had been precocious and furious (especially for a child), political and full of feeling, biographical and muscular. It was a nutritional life. But the words he fed himself with were clothed in flame: Manchild in a Promised Land, The Autobiography of Malcolm X, Soul on Ice, The Fire Next Time, Native Son. He chose them deliberately. It was as if he knew he had no time for dainty, pretty, peace-loving words. He read the books raw, in their passion and rage for life—which was how he saw himself, too. When schizophrenia took hold, he closed the book on his books and became preoccupied with inner violences. Then, when he lost his vision, he seemed to be opening the books again. Of course we immediately offered him a library on tape, lessons in Braille, any possible window into a future. There were thousands of books he could listen to. He pleasantly said he might consider it. Months have passed, he is still pleasantly considering, and we doubt he will make another decision. This is a piece about sight, a man who lost it, and what it meant to him. All his life, no one had known it, he was on fire. Elissa Ely ’88 is a psychiatrist at the Massachusetts Mental Health Center.

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SAVING FACE One study shows infants may be more skilled than adults at facial recognition. by Jessica Cerretani

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he six-month-old sits cradled on his mother’s lap in the dark, watching a succession of images flash across the television screen in front of them. But the colorful characters of Sesame Street and Yo Gabba Gabba aren’t what hold his attention. Instead, the child, whom we’ll call Tommy, is viewing a series of human faces; his reactions to them are part of an ongoing study about facial recognition. It’s the first of several visits Tommy and his parents will make to the Laboratory of Cognitive Neuroscience at Children’s Hospital Boston. And while the significance of his participation seems lost on the youngster— despite a mild cold, he calmly sucks on his pacifier throughout the hour-long session—

his responses will aid our understanding of how our ability to recognize and process faces develops. “Our faces contain a wealth of information, from our identity, age, gender, and race to our emotions and intentions,” says Charles Nelson, the lab’s director and an HMS professor of pediatrics. “For babies, who are still pre-verbal, much depends on the ability to recognize and read faces.” In fact, infants may be more skilled than adults at facial recognition, as Nelson and his colleagues discovered nearly a decade ago when they tested babies’ ability to discriminate between different human and monkey faces. Facial decoding skills develop during the first six months of life, when babies

can easily distinguish among human and monkey mugs, a talent that ebbs with time. By nine months, children can still differentiate between human faces, but can no longer recognize different monkey faces. That makes sense, says Nelson, who explains that our facial processing skills depend in part on our experience: The more we’re exposed to other people, the better equipped we are to distinguish between individuals. Unless we regularly hang out with monkeys, though, we’re apt to think they all look alike. To prove this point, Nelson gave a book of different macaque monkey faces to the parents of 13 six-month-olds and asked them to spend a few minutes every day showing their children the faces. Another 13 babies received no

macaque training. After three months, the babies who had regularly viewed monkey faces could differentiate between individual monkeys; the control subjects could not. The results, says Nelson, “show that our experiences play a huge role in what faces we can and can’t recognize.” Ongoing studies by Nelson and others analyzing our ability to differentiate faces of other races, ethnicities, and genders suggest similar effects. Such findings aren’t just cocktail-party fodder. Nelson’s research offers stunning insights into how our visual system develops. Back at the lab, Tommy is wearing a cap netted with electrodes, which measure how his brain reacts to certain visual stimuli. As a variety of faces bearing exaggerated emotions— joy, sadness, fear—flash across the screen, a computer program generates a graph based on his responses. If Tommy’s facial processing skills are similar to those of other babies his age, he’ll focus the longest on the fearful expressions, even though he doesn’t yet understand what they mean. Research suggests that babies are typically first attracted to fearful faces and later to other expressions, such as sadness, happiness, and anger. This decoding helps us form relationships and understand each other. Yet babies at high risk for autism—typically those who have an older sibling with the developmental disorder—appear to lack face-reading expertise. “We know that children and adults with autism tend to avoid looking directly at other people’s faces, particularly the eyes,” explains Nelson. “If they focus on anything, it’s the mouth or the edges of the face.” They also don’t seem to recognize faces as well: When exposed to images of their mother’s face or that of a stranger, most children are drawn to Mom’s visage. Kids at risk for autism, however, respond

harvard medicine ~ spring 2010 13


GET THE PICTURE? Humans may be more adept at

WHAT MEETS THE EYE Our ability to take

identifying caricatures than the real thing

b

ob Hope’s nose. Angelina Jolie’s lips. Jay Leno’s chin. For most of us, these features— and the famous faces that frame them—are instantly recognizable. Now, researchers are discovering what cartoonists and other artists have

known for years: We are adept at identifying caricatures of faces. In fact, says Margaret Livingstone, an HMS professor of neurobiology, we may often be more skilled at identifying caricatures of people than photographs of them. “Every step in visual processing involves the extraction of information from the world around us,” explains Livingstone. “But we remember extremes best.” That’s why artists exaggerate certain features. Take Pablo Picasso, for example. His painting of Gertrude Stein,

while abstract, is instantly recognizable to anyone familiar with the writer’s wide forehead and strong nose. There’s a scientific basis for this phenomenon. In one recent study, Livingstone and colleagues used functional MRI scans to identify an area of the brain in macaque monkeys called the middle face patch, which consists almost entirely of cells dedicated to face recognition. When the monkeys were presented with a series of real and cartoon faces, their face-selective neurons responded similarly to both. And in 45 percent of the cells, cartoon faces elicited the best or second best response compared to real faces. The findings, says Livingstone, show that caricatures convey a wealth of knowledge about individual identity through both the shape and spacing of certain features, like the curve of a mouth or the distance between eyes. “Our cells appear to be attuned such facial variables,” she says. “That’s why caricatures work so well.”

GAME ON Virtual spaces may help blind people navigate the wreal ones

v

ideo games aren’t just fun time sinks. Recent research suggests they may help the blind navigate virtual—and possibly real-world—spaces. In recent study, Lotfi Merabet and colleagues reviewed research in which blind people played computer games that employed audio cues such as footsteps and door knocks to guide players through a virtual maze. The subjects were then asked to use blocks to

14 harvard medicine ~ spring 2010

recreate the route taken in the games. The players were overwhelmingly successful at reconstructing the paths—evidence that they had created new cognitive spatial maps. Even more intriguing, MRI scans of the subjects’ brains showed activity not just in the expected auditory and sensory-motor regions, but also in areas associated with vision. Merabet, an assistant professor of neurology at Beth Israel Deaconess Medical Center,

in visuals may be only small portion of what is really there

v Losing Face

Imagine not being able to recognize your spouse in a crowd of faces or forgetting what your own child looks like. Sounds like an episode of The Twilight Zone, but for some people, such surreal events occur every day. Also known as face blindness, prosopagnosia—the inability to recognize faces—may affect as much as 2 percent of the population. In severe cases, people with prosopagnosia may not even recognize the faces of their own spouses or children. Brain injury can trigger face blindness and, for reasons that are unclear, the condition is present from birth in some people. Research by HMS cognitive neuroscientist Beatrice de Gelder and other investigators is helping to shed light on this intriguing disorder. One recent study, for example, suggests that smiles, scowls, and other emotional expressions may help prosopagnosics better recognize faces. De Gelder and her colleagues found that emotionally expressive faces activated certain areas in the brains of lifelong prosopagnosics, while neutral faces did not. Such findings “suggest that emotional information may play an important role in the way we process faces,” says de Gelder. “We are still discovering the extent to which facial expressions help prosopagnosics remember people they’re supposed to

ision, wrote Jonathan Swift, is the art of seeing things invisible. In truth, however, we may not even notice the obvious, says Jeremy Wolfe, HMS professor of ophthalmology and head of Brigham and Women’s Hospital’s Visual Attention Lab. Together with Todd Horowitz and other colleagues, he is identifying the ways in which we search for objects and detect changes in what we see—research that has real-world implications for fields as diverse as baggage screening and radiology. The researchers’ conclusion: We often miss what’s right in front of our eyes. “We believe we’re viewing the whole world,” explains Wolfe, whose lab studies a variety of visionrelated topics. “But we’re only processing a small part of it.”

We all perform visual searches every day, whether rifling through a drawer for car keys or assembling a jigsaw puzzle. But some searches—for a gun in an airplane passenger’s suitcase or a tumor on an MRI scan—are more crucial than others. Think the target in question would be clearly evident to searchers? Think again. Studies by Wolfe, Horowitz, and others suggest that the less common an object, the harder it is to spot it when it appears. “Targets like these are relatively rare,” says Horowitz, an HMS assistant professor of ophthalmology. “So we’re less likely to notice them when they do show up.” Based on findings from their laboratory research, in which volunteers are asked to locate unique letters or symbols on

a computer screen—a single letter “T” in a field of “Ls,” for example—Wolfe and his colleagues have expanded their experiments. In one study, published in the January 14, 2010 issue of Current Biology, they asked subjects to search for weapons in simulated baggage. The participants were given a likelihood of finding a weapon and were rated on both the time it took them to locate the object and their accuracy. The researchers found that subjects were quick to find weapons that they had been told were frequently present—to the point of identifying weapons that weren’t there—but took far longer to dismiss luggage when the odds of it containing a weapon were low. The origin of this phenomenon

may be rooted in genetics, Wolfe explains: Our caveman ancestors naturally focused on hunting the most common prey, with less attention paid to scarcer species. At the same time, if they knew a food source was nearby, they kept looking until they found it. But when these traits emerge today in more serious situations, they can have life-threatening consequences. The lab’s findings have practical applications for the ways in which airport security personnel are trained, says Wolfe. He is planning similar investigations among radiologists, whose search techniques tend to result in more false-positive reports of tumors. The research may also translate to other types of visual searchers, from Coast Guard

LEAD IN: A test devised by Jeremy Wolfe of Brigham and Women's Hospital and Harvard Medical School demonstrates a phenomenon known as change blindness: the frequent inability of our visual system to detect alterations to something in plain view.

harvard medicine ~ spring 2010 15


SECOND SIGHT Remarkable research suggests

VISION QUEST HMS discoveries have helped shape our vision of the future.

some blind people may indeed see

t

he man made his way down the hallway, maneuvering with ease around the boxes, chairs, and other obstacles in his path. For most people, this act would have been routine, one we perform countless times each day. The man’s journey, however, was anything but ordinary. He had successfully circumnavigated the clutter without a misstep—and he hadn’t seen any of it. Damage from two strokes had left lesions on both of the man’s visual cortexes, rendering him blind. Identified only by his initials, TN required a cane and his wife’s assistance to walk down the street. His performance in the obstacle course, part of an experiment assessing visual capacities in the blind, stunned investigators. “We were absolutely shocked by his ability to navigate the corridor,” says the study’s lead researcher, Beatrice de Gelder, a cognitive neuroscientist at both HMS and Tilburg University in the Netherlands. TN was surprised, too. “He hadn’t made any conscious effort to hear or feel his way around,” de Gelder explains. “This was all automatic behavior.” De Gelder’s study, published in 2008 in Current Biology, was the first to show in humans what had been reported previously in monkeys: that we may be able to detect aspects of our environment,

16 harvard medicine ~ spring 2010

even if we aren’t aware of seeing them—a concept known as blindsight. The result, says de Gelder, “illustrates in a fairly dramatic way that the brain has a number of alternate routes that can be mobilized when the main avenues to vision are blocked.” That’s because retinal cells appear to project images not only to the visual cortex, but also to other parts of the brain related to vision and emotion. For TN and others whose other cognitive functions and eyes remain intact, these areas may still respond to visual cues, allowing them to react to such stimuli, if not actually “see” it. Blindsight isn’t limited to navigational skills. Other research by de Gelder and her colleagues suggests that the blind may be able interpret facial expressions as well. Experiments with TN and other visually impaired people have shown that certain facial expressions—fearfulness, for example—can cause study subjects to cringe or otherwise react, even though they cannot consciously view those expressions. For de Gelder, who is planning further studies of TN this spring, such findings demonstrate the importance of looking beyond the obvious. “We tend to concentrate on the major visual systems in the brain,” she says. “But we may have hidden resources.”

1950

Risk Assessments

Could the humble light bulb play a role in the development of cancer? That’s the implication of a growing body of evidence that links breast cancer risk with exposure to artificial light. Now, two recent studies led by Erin Flynn-Evans and her colleagues at the Division of Sleep Medicine at Brigham and Women’s Hospital provide further insight into the subject. The first study looked at 1,392 blind women who either had no ability to perceive light or had some light perception. Sixty-six of the women had been diagnosed with breast cancer. After controlling for other risk factors, the researchers found that women with no light perception had a more than 50 percent reduction in breast cancer compared to their peers who could see some light. A related study of the same group of women showed that blind women with no light perception had their first menstrual period at a younger age than those with some light perception. The findings were surprising, Evans says, since earlier menarche is associated with increased odds of breast cancer in sighted women. Taken together, she adds, these findings suggest reproductive differences aren’t responsible for lower breast cancer risk in blind women. Further research is needed to elucidate how the body’s response to artificial

More than half a century ago, famed retinal surgeon Charles Schepens saw the need for a research organization dedicated to exploring new treatments for incurable eye disorders. Originally called the Retina Foundation, the HMS affiliate has since been renamed the Schepens Eye Research Institute for its founder and is the largest independent organization of its kind in the world

1959

Glimpses into a cat’s eye shed light on the way nerve cells respond to light, motion, depth, color, and other types of visual stimuli. With their studies of the feline visual system, David Hubel and Torsten Wiesel, both researchers in the then-new HMS Department of Neurobiology, laid the foundation for the field of visual neurophysiology and greatly expanded knowledge of sensory processing. Their work was recognized with the 1981 Nobel Prize in Physiology or Medicine.

1965

: When Lloyd M. Aiello, now an HMS clinical professor of ophthalmology, began treating patients blinded by diabetic retinopathy, his waiting room was filled with seeing-eye dogs—many of which outlived their owners. Now, the vast majority of people with the disease retain their vision, thanks to Aiello’s pioneering work. With his late father-in-law, he created the laser treatment known as panretinal coagulation, which uses a laser to halt the sight-stealing proliferation of blood vessels in people with diabetes. 1 line please

1965

When Lloyd M. Aiello, now an HMS clinical professor of ophthalmology, began treating patients blinded by diabetic retinopathy, his waiting room was filled with seeing-eye dogs—many of which outlived their owners. Now, the vast majority of people with the disease retain their vision, thanks to Aiello’s pioneering work. With his late father-in-law, he created the laser treatment known as panretinal coagulation, which uses a laser to halt the sight-stealing proliferation of blood vessels in people with diabetes.

1992

Thousands of patients have avoided blindness thanks to FDA approval of the Boston Keratoprosthesis, an artificial cornea developed by Claes Dohlman, former chief of ophthalmology at Massachusetts Eye and Ear Infirmary. His invention is used in people with severely diseased corneas when transplants from human donors fail.

treatment has improved over the years, thanks in part to the efforts of Joan Miller, chief of ophthalmology at Massachusetts Eye and Ear Infirmary. Along with her colleague Evangelos Gragoudas, she pioneered the use of photodynamic therapy to damage abnormal blood vessels in the eye without harming the retina. The approach, which was approved in 2000 as the first treatment for age-related macular degeneration, has reduced vision loss in many patients.

2006

The rich legacy of Judah Folkman ’57 is not limited to cancer treatment. Research on angiogenesis by the late investigator and others

at Children’s Hospital Boston led to the creation of the antiVEGF drug Lucentis for the treatment of age-related macular degeneration. The U.S. Food and Drug Administration approved the medication after data showed it might not only slow vision loss but also restore sight in some patients.

2010

The rich legacy of Judah Folkman ’57 is not limited to cancer treatment. Research on angiogenesis by the late investigator and others at Children’s Hospital Boston led to the creation of the antiVEGF drug Lucentis for the treatment of age-related macular degeneration. The U.S. Food and

1994

Like father, like son: A third-generation ophthalmologist at Joslin Diabetes Center and HMS, Lloyd P. Aiello has spearheaded his own research into the roots of vision loss. His studies have shown that vascular endothelial growth factor, or VEGF, plays a major role in the proliferation of blood vessels in eye diseases including diabetic retinopathy and agerelated macular degeneration.

2000

Age-related macular degeneration is still the leading cause of blindness in older adults, but its

harvard medicine ~ spring 2010 17


the senses: auditory

5

the

ounds of

ilence by sanjay gulati

Modern neurobiology suggests that the human senses are both more numerous than the five Aristotle identified and less distinct— they can overlap and intertwine. Lip readers like me, for example, experience seeing as hearing. My mind creates an audible voice for everyone I meet. I once “heard” the high, melodic voice of an androgynous woman. When it dawned on me that she was, in fact, male, the voice I imagined dropped an octave. On another occasion, I finally caught the word “London” on the lips of a young scientist with whom I had been struggling to converse. The word triggered a mental filtering; when I reassigned him a British accent and diction, he grew audible.

Those without sound can hear vibrations, the motion of lips, and the dance of expressive hands 18 harvard medicine ~ spring 2010

harvard medicine ~ spring 2010 19


Hearing around corners and through walls has

been replaced, in part by acute awareness of vibrations. I began losing my hearing during adolescence and by early adulthood, I had become deaf. My musical training has stayed with me—I can play a symphony in my head, or a fugue at the piano, despite my inability to hear. My senses of physical, social, and linguistic space have changed remarkably, though. Hearing around corners and through walls has been replaced, in part, by an acute awareness of vibrations. I hallucinate a soundtrack for life, hearing footsteps, a teakettle’s whistle, and even road noises while driving, which I sometimes forget to turn off when the car stops. Aspirated consonants are those accompanied by an audible puff of air: the p in spot, for example, as compared with that in stop. Remarkably, a puff of air on the back of the hand can make listeners perceive an un-aspirated consonant as aspirated: Our minds link hearing with touch. Sound is vibration, and physical vibrations can often be heard. Deaf people dancing at parties sometimes hold balloons, whose light vibrations transmit the music’s beat and bass line. The more readily I can predict a speaker’s words, the better I will hear them: “Paper or plastic?” is easy to catch at the cash register. The frustrating corollary is that the most interesting information often becomes the most difficult to hear: I hear the joke but miss its punch line. In a final, convoluted example operating in the opposite direction, what I think I hear can change what I see. I was raised into spoken languages and acquired American Sign Language only as an adult, so my mind still gives lip reading priority over signing. I can be blind to perfectly clear sign language when I see a different word on a speaker’s lips.

Subhead A deaf person’s broken ears can seem tragic to hearing people. A nonsigning person’s inexpressive hands can be just as tragic to signers. The natural existence of sign languages among groups of deaf people who experience themselves as entirely ordinary is a stunning anthropological and linguistic challenge to the only form of normality that most hearing people know. [sentence needs serious recrafting!] “We have a hard-of-hearing patient at our outpatient psychiatric clinic,” a colleague in Germany writes. “She has a cochlear implant and has trouble benefiting from her therapy group of hearing people. She has been rejected because of her hearing disability so often, Any advice on treating someone with special language needs in a ‘non-special’ group setting?”

20 harvard medicine ~ spring 2010

This clinician’s dilemma illustrates the easily overlooked social dimension of hearing. Real hearing exists on a continuum, from the supernormal hearing of many children and musicians, through the many degrees of hearing impairment and deafness, to the rare cases in which hearing is entirely absent. [author: clarify the difference between deafness and the entire absence of hearing?] Social hearing, however, has its own rules. For hearing people, the long-ago acquisition of language was effortless and its current use largely unconscious. Yet a line hovers somewhere around being able to use the telephone and to make dinner-table conversation, and those with hearing above the line are often unkind to those below. I can only advise my colleague to help her patient to recognize this isolation as society’s difficulty in accepting those who are different rather than a problem of her own creation. I serve as a consultant psychiatrist to the American School for the Deaf. In the surrounding community of West Hartford, Connecticut, as in other communities with large numbers of deaf people, the culture has shifted toward inclusivity. Instead of floundering in discomfort, local restaurant and store employees communicate flexibly with deaf customers, writing on tablecloths, using rudimentary sign language, and accepting some awkwardness. As a result, the deaf person feels invited to belong to society. Disability does not inhere within the body; it is created equally by bodily status and society’s response.

Subhead The most disturbing presenting symptom among the deaf patients in my psychiatric practice—and the focus of my current research—is language dysfluency that has been caused by language deprivation. Children learn sign languages, like spoken languages, remarkably early, with a nearly complete comprehension of grammar—the engine of language—by age three. Yet children not exposed to usable language by three or four will never learn any language fluently. And one with no exposure by seven or eight will be mentally retarded. [author: will they be considered literally mentally retarded or its equivalent?] Sound is not language. Breathless headlines about a child “hearing for the first time” skip over the chasm between the two. We know little of the process by which our innate capacity for language encounters a mother tongue, transforming us into linguistic beings. Children can be deprived of language when hearing aids or cochlear implants provide inadequate sound. They can be deprived by skimpy early intervention services or by teachers who persist with failing educational methods. Children can be deprived by grieving parents who cannot bring themselves to learn sign language or by polemical parents who refuse to learn. Whatever the cause, the results can be tragic, all the more so for having been sanctioned by medical and educational authorities. A young man who was not exposed to sign language until the age of nine once signed to me, “That in a you know people me deaf same want want that you know stay family love lost communication fail.” Straining, my interpreter and I guessed that he was trying to say that

THE DANGERS OF A MISSPENT YOUTH

Researchers uncover the crescendoing costs of early noise exposure

l

ady Gaga mounts the stage in a revealing, sequinstudded corset. Bleachedblond bangs hide her eyes while short black boots accentuate her long, bare legs. She pauses, then an explosion of drums sends her hips gyrating. With a gloved fist pump, the high-kitsch diva begins belting out the opening verse to “LoveGame.” Teen nirvana. Later that evening, a young fan returns home to dream of life as a pop phenomenon. But she’s distracted by a ringing sensation in her ears. By the next day, the discomfort dissipates, her hearing returns to normal, and she’s left only with positive memories of her evening of auditory excess. New research,

however, suggests that our ears hold grudges longer than once thought: Hearing may continue to deteriorate months, or even years, after an insult occurs. “Until recently, we accepted the dogma that noise has a time-limited effect,” says Sharon Kujawa, an HMS associate professor of otology and laryngology and director of audiology at the Massachusetts Eye and Ear Infirmary, or MEEI. Recent studies in mice by Kujawa and her colleagues are challenging assumptions about noise-induced and agerelated hearing loss. Their work promises to inform future treatments. Kujawa’s office lies at the heart of the the audiology unit of MEEI, just steps from

the entrance to a clinic where doctors help patients adjust to hearing loss. And the clinic is brimming with people complaining of communication problems caused by noise exposure or aging. An estimated ten million people in the United States have permanent hearing loss from noise or trauma [if not age related, remove reference in previous sentence?], and Americans are losing their hearing earlier than they did in the past [how long ago?]. Thirty percent of adults aged 65 and older have trouble hearing. Kujawa has worked with M. Charles Liberman, the Harold F. Schuknecht Professor of Otology and Laryngology at MEEI, to probe the relationship between noise-induced and age-related

hearing loss, processes long assumed to be additive rather than multiplicative. Clinicians had assumed, for example, that miners suffering from permanent threshold shift, or reduced sensitivity to pure tones, could stabilize their hearing loss by switching to office jobs. According to auditory doctrine [of that time?], any further hearing loss, including hearing loss later in life, was unrelated to the original workplace exposure. Kujawa and Liberman made a surprising discovery, though, when they monitored genetically identical mice for months after subjecting the adult animals to loud sounds. The fleeting auditory insult—roughly akin to a blaring Lady Gaga concert— accelerated age-related hearing loss. “Initially, we thought that some of the mice had dodged a bullet because their thresholdshift sensitivity returned to normal a few days after the insult,” says Kujawa. But even those “lucky” ones lost their hearing more rapidly as they aged than did mice with virgin ears. Additional research has since provided a possible explanation for these observations. Again working in mice, Kujawa and Liberman detected small changes in the neurons that convey messages from the sensory receptors—or hair cells—of the inner ear to the auditory nerve and brain. The animals still had picture-perfect hair cells, but their auditory neurons [lacked? Shoed damage to?] were missing some of the spindly extensions that store and release chemicals called neurotransmitters. The disappearance [shutdown?] of these nerve terminals foreshadowed a bigger problem. After a number of weeks, the mice began to lose auditory neurons. “These mice could still detect pure tones administered in a quiet setting,” says Kujawa, “but they lost processing power.”

harvard medicine ~ spring 2010 21


MUSICAL MEDICINE Perfect pitch provides

Ear Splitting

clues to the way our brains function

p

syche Loui studies brains—including her own. That’s because she belongs to the very class of “animal models” that she and her colleagues research. Loui works with Gottfried Schlaug, HMS associate professor of neurology at BIDMC, and director of the Music and Neuroimaging Laboratory. Schlaug gets deep into the heads of musicians, or, as he calls them, “auditory-motor athletes.” Loui’s brain is of particular interest to the team not simply because she’s a violinist but because she also possesses a rare trait that is the envy of most musicians: perfect pitch. Hum any note in her presence, and she can immediately tell you that you’re humming, say, a slightly flat G-sharp. She can discern notes as easily as the rest of us can tell chocolate from vanilla. Musically, perfect pitch exists in a class by itself. Most people can learn an instrument at any

age (although, like language, the younger you are the easier it is). Not so with perfect pitch. If you don’t have it, you’ll never get it. Loui, an HMS instructor in neurology at Beth Israel Deaconess Medical Center, herself fits the demographic of many people with perfect pitch: she began musical training at a very young age, and she grew up speaking a tonal language, in her case Cantonese. But Loui’s brain actually looks different from the brains of most people. In fact, finding out that musicians with perfect pitch have certain morphological distinctions that can be discerned with an MRI was one of the foundational discoveries of Schlaug’s group. In the 1980s, the theory that the right hemisphere of the brain housed a person’s creativity, while the left hemisphere processed things like math had taken hold among neurologists. Following this line or reasoning,

musicians should then be highly right-brain lateralized. Researchers believed that the actual structure of the brain evidenced this. In the early 1990s, Schlaug decided to test this claim, and recent advances in MRI technology provided the means. Scanning the brains of both musicians and nonmusicians, Schaug and colleagues discovered that, morphologically speaking, his colleagues had it backwards. Not only were musicians, on average, more “left brained” than non-musicians, but those with perfect pitch were the most left-brained of all. The focal point of Schlaug’s investigation was a part of the brain called the planum temporale, a chunk of grey matter residing in auditory cortex, a region used as a measure for brain dominance. In musicians with perfect pitch, the planum temporale in the left hemisphere was, quite

PSYCHE LOUIS caption continues caption continues caption continues caption

22 harvard medicine ~ spring 2010

literally, bigger than the planum temporale’s of musicians without perfect pitch, and certainly bigger when compared with nonmusicians. “Think about it,” says Schlaug. “Professional musicians practice their skills many hours a day, for many years. How does that affect their brain organization? With that first experiment almost twenty years ago we began to understand that the structure of a person’s brain could correlate with how dedicated they were to practicing a particular skill.” These findings launched Schlaug onto a research trajectory that today has led to collaborations with Loui and other musician/scientists who are looking for the therapeutic potential of music’s ability to shape the brain. An elderly man has a lesion on his left frontal lobe, the collateral damage of a massive stroke that’s robbed him of the ability to speak. A clinician sits across from him asks him to simply repeat the following phrase: “Happy birthday to you.” He struggles admirably, but in the end only manages, “En oh en oh en oh.” She then asks him to sing it. Holding his left hand inside of hers, moving it up and down to the rhythm of this childhood melody, she initiates the song. After two or three attempts, she is silent, and he, solo, sings it as clearly and coherently as anyone anywhere sitting around a cake wearing a party hat. The clinician then asks him, once again, to speak the phrase. Without a hitch, he says to her, “Happy birthday to you.” It’s hard to watch this video clip without gasping in awe. In less than two minutes, you’ve witnessed an extraordinary therapeutic feat.

MISGUIDED BY VOICES

Touch working in unison with other senses are our most effective way of reading stimuli

f

or weeks now, the very air around her had seemed ominous. When her doctor scheduled routine blood work, she had felt a stab of suspicion. And at the clinic, when the seemingly harmless phlebotomy tech asked her to make a fist so he could prod her forearm for a vein, a queasy dread bloomed in her stomach, And then she heard them. A fluttering of voices, hushed, secretive, drifting from the air vent in the ceiling. “We should do it now,” one of the voices whispered. “Yes,” hissed the other. “She’s right here. Let’s do it.” The tech turned, syringe in hand, and suddenly her qualms made complete sense: She was in the midst of an extravagant medical experiment. And everyone was in on it. She bolted from the clinic. This incident illustrates what a patient, typically one suffering from schizophrenia, will report when describing auditory hallucinations. Such patients can pinpoint exactly where the voice is coming from, whether it’s next to them, above them, or down the hall behind a closed door. They can say whether the voice sounds male or female. And they confirm that the voices are always hostile. Yet according to Dost Ongur, an HMS assistant professor in psychiatry at McLean

Hospital, just because it’s a hallucination doesn’t mean it’s a delusion. [clarify difference] “These patients actually hear something,” he explains. “They don’t just imagine voices. All auditory circuits in their brain are fully engaged. The only thing missing is the external stimuli.” Brain scans confirm this finding. David Silbersweig, chair of the Department of Psychiatry at Brigham and Women’s Hospital, and others have found that when patients experience auditory hallucinations, their primary auditory cortex, the region of the brain that receives direct input from the ears, is fully activated. Conversely, another region of the brain called the anterior cingulate cortex, a region that differentiates external from internal stimuli, appears to break down. “It’s a twofold mechanism,” says Ongur. [what is his research? why is he our guide?] The origin [of?] is unclear. Very likely, abnormalities occur in the brain during key moments of development. In fact, postmortem analyses of patients often show cellular abnormalities in these very brain regions. For now, clinicians can treat symptoms [of auditory hallucinations?] with drugs that regulate dopamine activity, but such treatments don’t address the source. “I wish we knew what caused this,” Ongur

In a restaurant or at a party abuzz with chatter, it is easy to zone out of the immediate conversation and listen in to another nearby discussion that catches the interest. That capacity to tune in—or tune out—single sound sources among many in a noisy room is called selective auditory attention, and it is where SeungSchik Yoo, associate professor of radiology at Brigham and Women’s Hospital, and his colleagues turned to learn how much control individuals can exert over their own brains. With the help of nearly instantaneous biofeedback, most people in two small studies learned to listen better—or at least boost the auditory portion of their brains—and retain the skill for at least two weeks, the researchers found. Yoo sees these preliminary results as a proxy for the broader potential of noninvasive ways to improve other aspects of brain function or to overcome brain damage or certain neurological diseases. In the experiments, participants wore special goggles showing real-time data in bar graphs from functional magnetic resonance imaging of

harvard medicine ~ spring 2010 23


BACK FROM THE DEAD Harvard researchers are seeking to regenerate sensory cells of the inner ear

h

earing loss isolates countless people by interfering with communication. For those willing to seek assistance, hearing aids or cochlear implants offer a reprieve from their muffled world. Both devices serve as workarounds for missing hair cells and auditory neurons, the delicate structures of the inner ear that receive, amplify, and translate sound into electrical signals for processing by the brain. But they treat the symptoms of the problem, not the underlying cause. Researchers at Massachusetts Eye and Ear Institute and the Harvard Stem Cell Institute soon hope to offer patients another treatment option in the future—drug cocktails that coax the inner ear to grow new sensory cells. Albert Edge, an HMS associate professor of otology and laryngology, and his colleagues study the stubborn

adult stem cells of the cochlea in culture dishes. These wallflowers lie dormant in adult mammals. Although capable of dividing and transforming into sensory cells, they become inactive in the inner ear by the time we reach puberty, even when supplies of hair cells and auditory neurons dwindle. “We’re primarily using adult stem cell cultures as tools for drug discovery,” says Edge. His team maps the process by which these blank slates transform into cells with specific functions, identifying factors that push the unspecialized stem cells toward particular fates. The Edge lab and other groups discovered, for example, that activation of Atoh1, a transcription factor, transforms the hibernating cochlear stem cells into hair cells. Now they are searching for chemicals that boost Atoh1 levels. Working at the

24 harvard medicine ~ spring 2010

Harvard NeuroDiscovery Center’s Laboratory for Drug Discovery in Neurodegeneration, Edge’s team applied more than 100,000 chemicals to cell colonies and identified roughly a hundred that increased Atoh1 production. The next step is to validate the findings in cochlear stem cells. “Our ultimate goal is to identify chemicals that will activate patients’ endogenous stem cells,” says Edge. “We may need to administer a series of compounds to the inner ear to achieve the desired result.” And that effort would require sophisticated vehicles for drug delivery to the cochlea, which hides behind a blood-perilymph barrier [in the ear?]. Enter a team of auditory scientists and engineers from Mass Eye and Ear and Draper Laboratory. Inspired by advances in regenerative biology, the

MUSICAL NOTES ON HEALING Listen to This

A whistling teakettle, a yapping dog, a clap of thunder, a car engine starting. It seems like it should be easy to recall hearing any one of these sounds 15 minutes later. “People are pretty bad at remembering sounds,” says Michael Cohen, who recently reported the relative inferiority of auditory recognition memory in a study he led as a research technician in the lab of Harvard Medical School vision researchers Jeremy Wolfe and Todd Horowitz. People remember visual scenes amazingly well, routinely scoring 90 percent or higher rates when noting the previously seen images a rapid succession of thousands of pictures. Not so with sounds, Cohen and his colleagues found. “It’s not even in the same ballpark,” says Cohen, now a psychology graduate student at Harvard. The results were unambiguous, no matter what sounds: spoken words, music, and complex auditory scenes, such as talking in a pool hall. (In one dramatic experiment, blurry and unrecognizable images scored better on recall than distinctive and identifiable sounds.) The consistently lower score— about 64 percent recall on fewer than 100 sounds—led researchers to conclude that the brain processes sights and sounds in fundamentally different ways. pinkie finger). Not so with the control group, whose attempts

Playing the piano regularly affects this surgeon’s preformance on the operating table

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or Claudius Conrad, a surgeon who has played the piano seriously since he was five, music and medicine are entwined — from the academic realm down to the level of the fine-fingered dexterity required at the piano bench and the operating table. “If I don’t play for a couple of days,” said Conrad, a senior surgical resident at Massachusetts General Hospital who also holds doctorates in stem cell biology and music philosophy, “I cannot feel things as well in surgery. My hands are not as tender with the tissue. They are not as sensitive to the feedback that the tissue gives you.”

Running the Scales

Music may one day help read genetic output to diagnose maladies. Gil Alterovitz, a bioinformatician with Children’s Hospital Informatics Program, sets gene expression to music as a diagnostic tool. Through the Musical Gene Expression project, he anticipates a day when physicians and researchers will have access to real-time monitoring of gene expression, the process by which a gene’s DNA sequence is converted into the functional proteins of the

Like many surgeons, Conrad says he works better when he listens to music. And he cites studies, including some of his own, showing that music is helpful to patients as well — bringing relaxation and reducing blood pressure, heart rate, stress hormones, pain and the need for pain medication. But to the extent that music heals, how does it heal? The physiological pathways responsible have remained obscure, and the search for an underlying mechanism has moved slowly. Now Conrad is trying to change that. He recently published a provocative paper

cell. The problem is that when that technology arrives, the amount of data that will come with it will be immense. “There are going to be thousands of things to monitor, and we can’t expect a physician to be able to process all that information,” said Gil Alterovitz, the lead researcher on the project. “So we’re using music to reduce the number of variables from thousands down to just a few.” They use mathematical techniques, in the case of

suggesting that music may exert healing and sedative effects partly through a paradoxical stimulation of a growth hormone generally associated with stress rather than healing. In a 2007 study, Conrad tested the effects of music on a group of ten critically ill patients. Half of them listened through headphones to the slow movements of Mozart piano sonatas for an hour, and half heard no music. Those who heard music needed less sedation, and had reduced stress hormone levels, lower blood pressure and a lower heart rate.

colon cancer, for instance, to reduce the data from a group of nearly 10,000 genes down to just four combinations that they say represent virtually all the variability in the data. Each combination is then assigned a note. When three or more notes are played at the same time, they become a chord. When those chords are played across time, they become music. The researchers assign a harmonious sound to a normal, healthy gene network. When there are deviations in

the genes’ behavior -- such as the presence of disease -- the music sounds inharmonious. “Auditory information allows surgeons, anesthesiologists, and other physicians to be able to focus on their task and listen at the same time,” Alterovitz said. “Harmonious music has a background quality to it; inharmonious music captures your attention.” His system, he says, gives the user the ability to discern many pieces of information at once, and may have broader potential for other areas

harvard medicine ~ spring 2010 25


the senses:smell

5

the

catching bouquet What can wine connoisseurship teach doctors about diagnosis? by Michael A. LaCombe

20 harvard medicine ~ spring 2010

This how it would work. In the beginning, I’d ask the housestaff to page me if they

had a case of pseudomonas pneumonia or C. difficile enteritis. I might then reward them (those who saw it as a reward) with a brief bedside rounds on the odor of slightly turned red grapes (pseudomonas) or the more intricate coal-tar-in-the-horse-barn smell of clostridia. By keeping the nurses in the OR and endoscopy suites well-supplied with bagels and donuts, I could guarantee a page when gas gangrene or shigellosis appeared, and eventually, merely by sticking my head in the door, I could catch the rotten apples or rancid butter, nod my head, wink, and thank them. For the more arcane stuff, greater rewards were necessary: a bottle of wine, dinner for two out on the town, that sort of thing. These rewards I posted in the newborn nursery for example, or on the pediatrics ward, and so collected the wet-mouse smell of PKU, the more

uncommon odor of maple-syrup-urine-disease, and the subtle hint of halibut gone-by in tyrosinemia. This was great fun at first, as are all hobbies, but became a curse, as do most compulsions. Let me start from the beginning. As an intern, I had a modest interest in wine, a pursuit my colleagues knew of. Frequently they would ask me for a recommendation or two and I’d help them out by steering them toward an affordable Vouvray rather than the more pricey Pouilly-Fuisse. From this began a wine co-op. With thirty or so residents interested in an inexpensive mixed case of wine every month, I began a

harvard medicine ~ spring 2010 21


bouquet are not doing this to jerk their parents around. Oh, they’re jerking their parents around alright, but that’s not why. wonderful relationship with the big wine store between Kodak Park and Xerox in Rochester, and its then-new owner, Sherwood Deutsch. Buying thirty cases of wine every month made me one of his best customers, got me invited into the after-hours back room tastings with the heavy hitters from the hi-tech industries, and exposed me to the smell and taste of an incredible array of wines. This was how I found I had a tasting memory. It wasn’t just that I got the cedar-pencils and cigarbox hints in the roasted cherries of a Pauillac. I remembered those smells, as you might remember at song at your high school prom. And just as you might recall, from the notes of that song, whom you danced with and what you wore, the taste of a ’61 Pichon-Lalande brought with it all the associated memories—because, as the neuroscientists will tell you, the nose is wired to the limbic system which is somehow connected to prom nights and great restaurants. Many of the executives from Kodak and Xerox resented this talent of mine, or, more precisely, envied it. In wine-tasting it is incorrectly attributed to the connoisseur or bon vivant, whereas in medicine, anyone who strolls through endoscopy leading with his nostrils is merely considered strange. In both cases, it is a gift, no more than that. Some are born with it. Others are not. I began collecting wines. Logical enough, although quite a pain when moving from place to place as young doctors usually do. I drifted toward cheeses and their smells and tastes, often filling the house with the so-called stench my wife ascribed to epoisses and livarot. And vacations, holidays, and weekends I secretly planned with the collection of smells in mind. I heavily lobbied for a vacation in China, ostensibly to see the Great Wall which they see in space but which we have never seen, with a side-trip to Xing’an County, where there were problems with typhoid. I needed its freshly baked black bread smell for my collection. Likewise Brazil could be lovely at a certain time of year, and if my wife might be happy with the shops in Rio, I could explore the butcher-shop smells of the yellow fever epidemic in Brasilia. (Aside: not the charcuterie smell of those wonderful shops in Paris, but rather, your basic, off-putting odors of the back streets off Mott Street in Chinatown.) My wife put up with this. But I was creating a monster of greater proportion. It had to do with that limbic system business I mentioned. I found myself avoiding bakeries heavily into sourdough bread, and then by association, all bakeries, because of the memories of that orphanage

22 harvard medicine ~ spring 2010

in Casablanca and those kids with pellagra. Eastern European restaurants also made the Index. The cooked cabbage conjured up hypermethioninemia. Italian restaurants heavy into garlic—just too reminiscent of that awful case of arsenic poisoning in northern Maine. I think you get the idea. My wife became suspicious of any travel suggestion. Both of us wearied of Irish meat-andpotatoes pubs. I longed for a wheel of Brie, but couldn’t bear the image of yet another abscess. It was with this heavy burden that I found myself on rounds the other day. The housestaff and their teaching attending had asked me to weigh in on a case that had them all puzzled. I was old, they hinted, had seen everything. Could I render an opinion? “Hello. I am Dr. LaCombe. I’m a cardiologist, but I understand there is nothing wrong with your heart. It’s just that your doctors have asked me to see you. I’m old, you see. I’ve seen everything.” “I’ve seen so many doctors, had so many tests. Maybe I should go to Boston. Should I go to Boston?” asked this sweet, pleasant old lady, redolent of Chanel No. 5. “What are you looking for?” she added. “The paperwhites. I smell paperwhites.” “Oh, my daughter threw them out yesterday. What’s wrong with me?” I hadn’t a clue, but I said nothing. I had read her chart, run through her history. I took another history. Nothing new to add. I asked all the wacko questions—travel, herbal meds, occupational/industrial exposure. She hadn’t been in any silos, hadn’t visited Paraguay. She started to look at me like the patients in the endoscopy suite. I began the physical exam, taking her hands in mine as I always do to begin. I scrutinized her fingernails, scanning them for diagnostic clues, but mostly stalling. No Muehrcke’s Lines. Nothing on her skin. I looked in her hair, at her scalp. She jerked away. “What are you doing? I don’t have lice! What are you looking for?” I didn’t know what I was looking for. I was still stalling. I said nothing. I began to examine her heart, listening at the base, then rolled her on her left side to listen at the apex, leaning over her, closer, closer still. “You’re smiling,” she said. “Why are you smiling? Did you hear something in my heart?” “What’s that smell?” I answered. Michael A. LaCombe ’68 is a cardiologist at Maine General Medical Center. The University of Maine Press recently published his latest book, Bedside: The Art of Medicine, a collection of medical stories. He assures us that this story is real.

MEMORY CARRIED ON THE WIND

Cambodian survivors of the Khmer Rouge continue to suffer from olfactory-induced panic attacks

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he four years that closed the decade of the 70s were ones of death and destruction for the people and the nation of Cambodia. During that time, a Communist-inspired revolution swept the Southeast Asian country, killing upwards of 1.7 million people. Among the many slogans driving the Khmer Rouge, the revolution’s guerilla force, and its leader Pol Pot was one that admonished “What is rotten must be removed.”

While the Khmer guerillas nearly succeeded in removing all people they considered rotten, they did inflict their legacy of brutality on many who did survive through memories based on the smells of destruction, such as decaying bodies, gasfueled pyres, and the sulfur and charred vegetation of mortar attacks. Many survivors can be so shackled to these olfactory memories that a whiff of the most innocent odor—composting trash, escaping fumes from a car’s

gas tank, a burning cigarette— will pull them into panicked states of vivid recall. To get a better understanding of the mechanisms behind olfactory-induced panic attacks, Mark Pollack, an HMS professor of psychiatry, and Devon Hinton, an HMS associate clinical professor of psychiatry, both with Massachusetts General Hospital, interviewed Cambodian refugees whose odor-triggered panic attacks had led them to a psychiatric

clinic in Lowell, Massachusetts. Their conversations revealed a complex network of causes—a multimodal model that combined symbolic, social, and psychological influences— behind the panic attacks. To help sufferers gain control of their odor-induced flashbacks, the researchers recommended a therapeutic schema that included teaching victims to graft troubling odors to pleasant experiences, to develop a coherent narrative for discussing their fears, and to practice mindfulness exercises for relaxation and control. The scientists also call for more investigations of olfactorytriggered panic attacks and

harvard medicine ~ spring 2010 23


Nothing to Sniff at

RACHEL WILSON caption continues caption continues caption continues caption continues caption and tktktktktk and some more

SCENTS AND SENSIBILITY

Neurobiologist Rachel Wilson follows her nose when looking for disease

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hen making diagnoses, doctors have always followed their noses. Hippocrates noted the body odor of his patients when identifying ailments. Avicenna used the smell of a person’s urine to detect illness. And in the early age of the house call, oldtime physicians made smelling patients part of their routine. At first whiff, such practices might reek of superstition, but intuitively and scientifically, they make sense. The bodies of sick people, like most objects in the physical world, produce volatile chemicals that can be identified by smell. Chemical analysis has shown that the

24 harvard medicine ~ spring 2010

breath of early-stage lung cancer patients, for instance, has a characteristic chemical consistency that gives it a particular odor. The same can be said for the urine of bladder cancer patients. Hoping to make use of these chemical fingerprints, researchers are exploring ways to sniff out disease. Some are studying cancer-sniffing dogs, which have been shown to diagnose illness with surprising success. Others have spurned the hairy and unpredictable business of doggy diagnostics in favor artificial noses, hoping to develop non-invasive devices that consistently detect disease. Such devices are currently in the testing stage.

However, their development has been stunted by one basic problem: relatively little is known about our sense of smell. Enter researchers like Rachel Wilson, an HMS associate professor of neurobiology. The MacArthur Fellow is one of a growing number of scientists who are making olfaction the focus of their research. Historically the neglected stepsister of sensory research, olfaction as a field has grown substantially since the first olfactory receptor genes were discovered in 1991. That discovery opened the door for Wilson and others to study our sense of smell at the molecular level. Wilson’s team is contributing to this

new field by studying the relatively simple olfactory system of the fruit fly, Drosophila melanogaster. The lab is generally interested in how the nervous system collects olfactory information, and how that information is processed as it moves from the primary sense organs to the decision-making centers of the brain. In insects, those primary sense organs are olfactory receptors on the antennae (as opposed to receptors in the mammalian nose). Wilson’s team puffs odors at the antennae and, with the help of very fine electrodes, makes electrical recordings of the neuron activity both in the receptors, and in the brain as information is passed along for processing. By labeling specific groups of neurons with green fluorescent protein, and by manipulating or knocking out certain populations of neurons, the team is able to see how those groups of neurons respond when flies encounter odors. As they tinker with each distinct group, they can start to make inferences about the roles those neurons play in the olfactory system. The goal is to discover how the whole circuit is wired up. Wilson explains, “The basic questions we’re asking are, how does a neuron respond to odors? What odors does it respond to? How does it help to encode the olfactory world? And why does it respond that way?” Answering these questions will help researchers understand how the nervous system identifies scents, but it won’t necessarily explain our more complicated odor responses. With that in mind, Wilson’s lab has branched into behavioral experiments. In these studies, they’re observing how fruit flies act in response to odor stimuli. They monitor flies in flight, for instance, to see how flight patterns change as flies detect smells in the air. Or, they observe how flies navigate to various, competing odor sources. Ultimately, it’s these complex, behavioral questions that may be most relevant to the development of artificial noses. Learning how

the brain identifies smells might be useful for those building devices designed to diagnose illness, but in fields such as environmental quality management and law enforcement, where it’s important not just to recognize the presence of an odor, but to find its source, odor detection and navigation are also important issues. Discovering how biological systems accomplish these tasks so effectively could help as artificial nose technologies progress. Wilson thinks that this is one area where the differences between insect and mammalian anatomy could benefit research. Her lab has found that Drosophila respond rapidly to odor filaments in the air. These filaments emanate from odor sources like plumes of smoke rising from a candle. Since insects smell with their antennae, they gather information from these odor filaments on contact. They alter their flight path and wing beats as they fly into the plumes, revealing to researchers that they’ve detected an odor, and where they think the smell is coming from. In contrast, mammals draw odors in through respiration. Not only do we dilute and mix odors when we suck air into our bodies, we also disrupt the integrity of the filaments. (Imagine taking a suction cup to that plume of smoke!) Since the concentrations of these filaments reveal a lot about the distance and direction of an odor source, the mammalian system seems comparatively ill-equipped for odor detection and navigation. That’s why Wilson is surprised that more developers aren’t thinking in terms of the insect system when conceiving artificial noses. “They’re designing systems that tend to draw air in actively over the device’s sensors as if it’s respiration,” she says. “I think people should be working in parallel on systems where sensors respond to filaments quickly without creating turbulence in the air, because you can learn a lot by observing these filaments.” —Veronica Meade-Kelly

Although smell preferences are heavily influenced by personal experience, there’s evidence that they are, in part, genetic. Identical twins, for instance, tend to share the same opinion of the polarizing scent of cilantro, whereas fraternal twins’ tolerance of the herb often differs. Some of the sensations that people associate with odors are tactile rather than olfactory experiences. The burn of hot pepper, the soothing coolness of menthol, and the tear-inducing sting of chopped onions all result from irritation of the trigeminal nerve system, which senses pain and temperature in the nose and face. Unlike other senses, the olfactory system has a direct line to the emotional center of the brain: the olfactory bulbs protrude directly into the limbic region of the brain. Researchers have found that human sperm express some odor receptors, suggesting that sperm may find their way to waiting ova by scent. Humans have approximately a thousand different odor receptors, each corresponding to a different gene in the body. Although these genes take up a whopping 3 percent of the human genome, only about 350 of our odor receptor genes work.

They monitor flies in flight, for instance, to see how flight patterns change as flies detect smells in the air. harvard medicine ~ spring 2010 25


(CAN’T GET NO) OLFACTION Sure, she’s pretty. But how does she smell?

h

ey, Miss—you, with those googly red eyes! Wanna dance? Wouldn’t it be nice if you could manipulate another’s mood with a waft of perfume, turning a stranger from standoffish to sweet? Sirens since Cleopatra have tried, with mixed results. Yet the fly and mouse manage handily. The question is, How? Ask Edward Kravitz, HMS professor of neurobiology. For a decade, he and his laboratory colleagues have been exploring how innate behaviors like mating, fending off suitors, foraging for food, and evading predators get pre-wired into the brain’s neural network. In the fruit fly, Drosophila

melanogaster, and in higher mammals, too, the sense of smell plays a key role in regulating behavior. Creatures communicate through a multiplicity of amines, peptides, steroids, and other signaling hormones called pheromones. A few found in flies and humans alike include serotonin and dopamine, controllers of the central nervous system. To study the link between genes and complex rituals of courtship and aggression, Kravitz and company tinker with fly DNA and videotape what happens. For example: Mutating a single gene known as fruitless, active in two neurons, alters the production of the pheromone octopomine. With octopomine levels ramped up, males that normally chase and shove their rivals now lunge like matadors; with levels dialed down, they meekly do the skedaddle. Using simple genetic techniques, the Kravitz lab

26 harvard medicine ~ spring 2010

has generated thousands of fly types with as many different mutations. “Neuron by neuron, we can ask, ‘what does each of these cells do’?,” Kravitz says. “We might stimulate an individual neuron and get a complex behavior.” Tweaking a few serotonin-producing neurons, for example, ratchets up aggression. Manipulating all 100 provokes a distinct set of seemingly unrelated behaviors, including odd table manners. Can fly routines carved into the DNA millions of years ago be overridden by novel experiences? What happens, for instance, when a fly goes a-courting, only to receive a whack upside the head? Fans of the Kravitz Fly Fight Club will have to wait for answers to be published in a leading journal later this year. Turning to Bob Datta now. Wouldn’t it be nice if you could manipulate another’s mood with a waft of perfume, turning a stranger from standoffish to sweet? Sirens since Cleopatra have tried, with mixed results. Yet the fly and mouse manage handily. The question is, How? Ask Edward Kravitz, HMS professor of neurobiology. For a decade, he and his laboratory colleagues have been exploring how innate behaviors like mating, fending off suitors, foraging for food, and evading predators get pre-wired into the brain’s neural network. In the fruit fly, Drosophila melanogaster, and in higher mammals, too, the sense of smell plays a key role in regulating behavior. Creatures communicate through a multiplicity of amines, peptides, steroids, and other signaling hormones called pheromones. A few found in flies and humans alike include serotonin and

dopamine, controllers of the central nervous system. To study the link between genes and complex rituals of courtship and aggression, Kravitz and company tinker with fly DNA and videotape what happens. For example: Mutating a single gene known as fruitless, active in two neurons, alters the production of the pheromone octopomine. With octopomine levels ramped up, males that normally chase and shove their rivals now lunge like matadors; with levels dialed down, they meekly do the skedaddle. Using simple genetic techniques, the Kravitz lab has generated thousands of fly types with as many different mutations. “Neuron by neuron, we can ask, ‘what does each of these cells do’?,” Kravitz says. “We might stimulate an individual neuron and get a complex behavior.” Tweaking a few serotonin-producing neurons, for example, ratchets up aggression. Manipulating all 100 provokes a distinct set of seemingly unrelated behaviors, including odd table manners. Can fly routines carved into the DNA millions of years ago be overridden by novel experiences? What happens, for instance, when a fly goes a-courting, only to receive a whack upside the head? Fans of the Kravitz Fly Fight Club will have to wait for answers to be published in a leading journal later this year. of their life. For many of us this is good news. According to Loui, “I think it’s fair to say that unless you’re tone deaf, you’re probably a musician in some sense of the word.” —Karin Kiewra

STOP MAKING SCENTS

Quality of life can take a nose dive when illness blocks the olfactory sense

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t’s a subtle sense, the sense of smell. We tend not to give it much thought or to think of its role as circumscribed, reserved for savoring the little luxuries of life—the perfume of violets, the aroma of hot chocolate, the milkiness of a newborn. But like its perceptive cousins, the olfactory sense protects and serves us—detecting the whiff of leaking gas, for example, or the notes in the concert of flavors we ingest. So it’s not surprising that patients with an olfactory disorder that reduces their ability to smell—as in anosmia’s absence or the hyposmia’s dimming—or changes it—as with the odor-altering parosmia or the smellconjuring phantosmia—report a slump in life’s quality. Yet therapies to correct wayward scents

lag, a fact that led Eric Holbrook, an HMS assistant professor of otology and laryngology at Massachusetts Eye and Ear Infirmary, to review what was known about the cause and treatments of smell disorders. In his look at the literature, Holbrook found that the vast majority of olfactory dysfunction cases result from head trauma, upper-respiratory infections, or chronic rhinosinusitis and polyp formation. Holbrook, underscoring the importance of isolating cause, cites links between neurodegenerative diseases and olfactory dysfunction. His findings indicate olfactory biopsies may aid in diagnosing earlystage Alzheimer’s disease. And although Parkinson’s close links to olfactory loss are acknowledged, Holbrook’s research shows

that testing for smell loss doesn’t become a sensitive indicator for development of the disease unless the testing occurs seven or fewer years before motor issues arise. Therapies for loss from non-neurological causes focus on surgery, for the removal of blockages, and on steroid use, with improvement from oral steroid use outstripping that from topical steroid sprays used alone or in combination with oral steroids. With continued research on how smell loss happens, Holbrook notes, better interventions can be developed, putting the delights and dangers of odors back into more lives. —Ann Marie Menting

harvard harvardmedicine medicine~ ~spring spring2010 2010 27 27


children are not doing this to jerk their parents around. Oh, they’re jerking their parents around alright, but that’s not why. ways of being a picky eater, and all of them, I would venture to guess, are more or less heartfelt. That is, children are not doing this to jerk their parents around. Oh, they’re jerking their parents around all right, but that’s not the why. I have noticed that often when I ask graduate students to write personal essays, many of them write about a food aversion going back to childhood. No one understood, no one believed, but they hated chocolate, or fruit, or something considered a delicacy. The more limited their tastes, the more clearly they remember being misunderstood, being pushed to try what they knew they didn’t like, being forced into the same defensive conversation over and over. Pediatricians take it as our business to direct parents on how to start solid foods. And to be honest, that concept— start solid foods—is firmly embedded in a particular moment and in a particular culture. What we tell parents now is a little bit different from what we told them even twenty years ago, though it follows certain basic lines, yes, start solids in the middle of the child’s first year of life (ideally around six months), start one new food at a time. We used to advise avoiding eggs and citrus for the first year; now we don’t. But mostly we all believe that you start by offering children bland and mushy foods and you work your way slowly toward color, texture, anything that’s sharp or spicy or bitter or umami-ish. But not all children have read the playbook. Some grab barbecued spareribs off a parent’s plate (that was my daughter), or beg for spoonfuls of the hot spicy soup before they have any words, or lick the deli mustard off a parent’s pastrami sandwich. And other children reject anything and everything, according to their own mysterious neuronal code: nothing too hot or too cold, nothing green, nothing with real texture. You name the exclusion, and someone in the room has a preschool child who follows that rule as if it had come down from Mount Sinai (speaking of famous food prohibitions). Some of the more familiar you know: there are the children who do not eat anything green. I have a friend whose nine-year-old will send back a pile of French fries (his favorite food, and at certain times in his life, his only reliable food) if the restaurant, in an upscale excess of enthusiasm, has sprinkled them with tiny bits of fresh parsley. And then there are those who don’t do spicy—though, to be honest, many adults don’t do spicy. And there are entire cultures, of course, where everyone—children and adults—cheerfully does spicy. And then there is the infamous “white diet.” I think of this as pretty much the ultimate picky eater state, more extreme than the anti-

4 harvard medicine ~ spring 2010

greens. These kids eat white bread, they eat noodles (sometimes with melted butter), they eat chicken fingers and French fries (if you don’t sprinkle them with parsley or paprika or some other evil substance) and of course, they occasionally indulge in vanilla ice cream. But the really interesting thing about the white diet is that each child invents it anew, cutting his teeth, so to speak, on rice cereal, and moving on from there to other varieties of—let’s face it—pap, whether served hot or cold, loose in a bowl or fried in strips. The true white diet child makes no exception for ketchup either (how loud, how red, how tasty!) Picky eaters require special meals, force their parents to carry supplies along to restaurants and birthday parties, and engender a certain moral righteousness. The world is full of people who will look at your picky eater and assume it’s all your fault. You didn’t set limits, did you? You acceded to his request and made him special dishes, didn’t you? A pediatrician friend told me a story about two mothers whose children she cares for—the mothers are sisters, and one has a white-diet child. The mother comes in and talks to the pediatrician about how restricted her child’s diet is, how worried she is that her child is falling off the growth curve, what a pain it is that wherever she goes, she has to bring along a little container of one of this child’s few foods, so that the child will consume a couple of calories. The mother’s sister then complains to the same pediatrician about how offended she is that her sister always brings food when she comes to visit, which she takes as a comment on her cooking abilities. “What I say to people in the office is just keep putting stuff on the table that you want her to eat—if he doesn’t eat it, he’ll have a bowl of cereal before he goes to bed, he’ll make some mac and cheese,” my friend said. We speculated about whether picky eaters are more common than they used to be: would our mothers have put up with this? Would our grandmothers? I remember two categories of children from when I was young: “he’s a good eater” and “she eats like a bird.” Presumably the eats-like-a-bird kids were the picky eaters. I have watched parents struggle, sometimes over the course of years, with children who do not like most of the things that delight the rest of us. In extreme cases, I have worried about the child’s growth and the child’s health and the child’s hematocrit; much of the time, I have just worried about the daily dinnertime struggles, the tension that develops between parent and child, and the complications of personal preference and family life. And I have felt sad sometimes for children

Breath by Chocolate

THE PHANTOM GOURMET

for some patients with psychotic disorders, mysterious tastes are part of daily life. by Elizabeth Dougherty

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mm. That first sip of coffee in the morning. The taste of butter on sourdough toast, perhaps with a dab of raspberry jam. [replace with more evocative foods?] Such flavors can make a person’s day—unless they arise unbidden, without the company of food or drink. For about 7 percent of patients with psychotic disorders such as schizophrenia, gustatory hallucinations—phantom tastes that arrive suddenly and fade just as quickly—are a common and disturbing part of life. Moreover, most phantom tastes aren’t delicious, according to Kathryn Lewandowski, an

HMS instructor in psychology at McLean Hospital, who evaluated psychotic patients to assess the type and range of hallucinations they experience as part of a large, ongoing study. Rather, the tastes are unpleasant and confusing. “Often patients experience a generically unpleasant taste,” Lewandowski says. “Some people do experience the taste of specific foods. But usually patients can’t identify the taste; it’s just generally disagreeable.” Clinicians have traditionally associated gustatory hallucinations—along with hallucinations of smell and touch—with brain tumors and lesions rather than with

idiopathic psychotic disorders. As a result, they often overlook such phenomena. With her study suggesting that gustatory hallucinations are also associated with certain types of delusions and an earlier onset of psychosis, a possible marker of more severe illness, Lewandowski recommends that clinicians ask patients whether they have experienced such sensations. “Patients don’t always report them freely,” Lewandowski says. “To fail to ask about them misses information that may be clinically relevant in terms of diagnosis but also just in terms of understanding patient experience and identifying

Your mother told you not to inhale your food, but if you want to indulge in the pleasures of chocolate without the attendant calories, you may just want to take a whiff. David Edwards, a member of the Wyss Institute for Biologically Inspired Engineering at Harvard, has created a mini-inhaler—dubbed Le Whif—that shoots a chocolate mist into one’s mouth, mimicking, he says, the experience of savoring the real thing. Edwards is known in science circles for designing a more efficient way to deliver inhaled medicines by tinkering with the particle sizes, and he has tapped that science in his lipstick-sized chocolate delivery gadget. The chocolate particles are small enough to shoot out of the brightly colored inhaler, but too large to make it to the lungs. Not only does this delivery system remove the guilt that comes with chocolate’s calories, he says, but it also moves us toward our culinary future. Evolution, he says, is trending toward smaller meals eaten more frequently—until chewing is pretty much replaced by breathing. “Breathing is eating,” he says. Of course, before dessert comes the main meal; Edwards has plans for inventing inhalable steak, carrots, and more. But for now, he is busy marketing Le Whif; a world tour is on tap. “The whole process is very

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A PINCH OF SALTthe receptors for the key flavor

SUPERTASTER SCIENCE

that makes everything taste better remains elusive to scientists. by Elizabeth Dougherty

m

odern synthetic chemists know better than to wave a pipette or gloved finger near their mouths. But in 1879, by and large, curiosity trumped safety. Case in point: Johns Hopkins chemists Constantin Fahlberg and Ira Remsen discovered saccharine in an accidental tasting. The reports vary, but only in the details—according to a 1927 article in Science, Remsen transferred the compound from lab to hand to dinner roll to mouth; according to an 1895 blurb in the New York Times, Fahlberg’s taste traveled from pencil tip to tongue. The serendipitous discovery led to four patents and went on to sweeten the once-popular soda called Tab,

among other things. But how, exactly, did Fahlberg (or was it Remsen?) physiologically detect that sweet taste? Until 2001, the cellular receptors involved in triggering the brain to detect a sweet sensation on the tongue were unknown. In fact, none of the cellular receptors for sweet taste was known until researchers—including a team led by Linda Buck, then an HMS professor—discovered them in 2001. Today, scientists have identified the taste receptor genes for four of the five tastes: Bitter, sweet, sour, and umami, or savoriness. The cells that make up taste buds on the tongue express these genes to create receptors that detect the molecular tastants, depolarize the cells, and trigger a signal to

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the brain. What remains to be understood is the one flavor that makes everything taste better, from cookies to grilled steak to butter: salt. “Candidate salty receptors have been proposed, but it is not clear that these are in fact the key mediators of salt taste,” says Stephen Liberles, an HMS assistant professor of cell biology who worked with Buck on the taste receptor work. [continue quote] Understanding these taste receptors [specifically for salt? or taste receptors in general?], the windows into our enjoyment of the best foods and our rejection of the vile, could help researchers develop safer tools than fingers and pencil tips for taste-testing new compounds.

genetics play a huge role in fussy eating habits. by Alice Flaherty

t

Menu Matters

You study a restaurant menu and decide to order the steak rather than the salmon. But when the waiter tells you about the lobster special, you decide lobster trumps steak. Without reconsidering the salmon, you place your order—all because of a trait called “transitivity.” Transitivity underlies rational economic choice, according to work done in the laboratory of HMS Professor of Neurobiology John Assad. According to transitivity, if you prefer lobster to steak, and steak to salmon, then you will prefer lobster to salmon. In the brain, transitivity is wired by neurons in the orbitofrontal cortex. They encode economic value in what HMS researchers call a “menu-invariant” way. That is, the neurons respond the same to steak regardless of whether it’s offered against salmon or lobster. “The activity of these neurons does not vary with the menu options,” says first author Camillo Padoa-Schioppa, a former HMS postdoctoral fellow. “This study provides a key insight into the biology of our frontal lobes and the neural circuits that underlie decision making,” Assad adds. “We can, in fact, compare apples to oranges, and we do it all the time. Camillo’s research sheds light on how we make these types of choices.” Scientists have linked “choice deficits”—such as eating disorders, compulsive gambling,

he proof is in the pudding. In The Luck of the Loch Ness Monster, picky eater Katerina-Elizabeth dumps her oatmeal over the side of an oceanliner each morning, and each morning, a sea worm gobbles it up, becoming larger and larger until he grows into the Loch Ness Monster. “Oatmeal is like slug slime, only lumpier,” says Alice Flaherty ’94, the author of the children’s book and a mostly unreformed picky eater. “My parents would boil Scottish steel-cut oatmeal for 45 minutes before we could eat it, and while it was boiling it would belch big oatmeal bubbles of steam into the air.” When she was little, Flaherty’s father told a version of the monster story to get her to eat her oatmeal. “Although I loved the story, it didn’t make me eat,” she says. “Now I have twin girls, one of whom is a picky eater like me, the other a normal eater like my husband. That got me interested in the biology of pickiness.” People often blame picky eating on children’s willfulness,

Flaherty says. Much pickiness is genetic, though, and sometimes even helps children stay healthy. Most picky eaters have a “supertaster” gene. If you have both copies of the gene, you taste flavors strongly, especially bitter compounds in foods like broccoli. If you have neither copy, you can’t taste those bitter flavors at all. Whether you’re a non-taster or a supertaster or somewhere in-between depends on your sensitivity to a bitter chemical called 6-n-propylthiouracil, or PROP. Non-tasters—about one-quarter of the population— cannot detect the bitterness of PROP at all. Medium tasters— half the population—can sense the bitterness but don’t mind it, while supertasters—the final quarter of the population—find the taste of PROP revolting. Children taste PROP more strongly than adults and, unlike adults, they always seem to sense the bitterness of the chemical. So it could be that certain flavours taste different to children than they do to most adults. This might explain why they’re

Taste the Burn

There’s a certain kind of magic in Thai food. The fire hits hard, then it fades. The taste buds beg for another bite. This enchanting cycle of fleeting and repeating self-torture and sweet relief continues, until—the bowl of Tom Yum soup drained, the last grains of rice devoured—you take your next shot at a peppery, lemongrassy adventure. The ancients who crafted these exotic herbal concoctions, it turns out, were culinary alchemists, pairing their seasonings to agonize—and to entice. Little did they know that centuries later scientists would still be working to tease apart the secrets of their savory mastery. Chemicals called tastants cause the burning sensation and subsequent cooling relief so common in Asian cooking. Capsacin, a chemical in peppers, triggers sensations of heat and pain by stimulating taste receptors on the tongue. Citral, a chemical in lemongrass, squelches that heat. Fans of hot, spicy food know that a sip of water amplifies

the peppery burn by helping the capsacin get onto [better verb] the taste receptors. Milk dampens the burn as its fatty lipids sweep some of the compound away. “Citral makes it not so hot, but in a different way,” says Stephanie Stotz, a research fellow in cardiology at Children’s Hospital Boston who described her findings in a May 2008 PLoS ONE article. Stotz found that citral blocks G protein-coupled receptors—transient receptor potential ion channels in taste buds—only after they have been activated and depolarized by, say, a tastant such as capsaicin. Stotz showed that citral blocks these open taste detectors in model cells. But the way citral blocks these receptors has a temporal component: it allows a quick surge of taste response—the burn—then dampens it for an extended time—the cooling relief. The molecular mechanisms governing the prolonged cooling effect of compounds such as citral remain a mystery. Yet unraveling these mecha-

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the

5 senses

What can the mystery of phantom sensations teach us about how our brains talk to our bodies?

The Man

MIRROR in the

by atul gawande

He was 48, in good health, when he made passing mention of an odd pain to his internist. For at least 20 years, H. said, he’d had a mild tingling running along his left arm and down the left side of his body, and, if he tilted his neck forward at a particular angle, it became a pronounced, electrical jolt. The internist recognized this as Lhermitte’s sign, a classic symptom that can indicate multiple sclerosis, vitamin B12 deficiency, or spinal-cord compression from a tumor or a herniated disk. An MRI revealed a cavernous hemangioma, a pea-size mass of dilated blood vessels, pressing into the spinal cord in his neck. A week later, while the doctors were still contemplating what to do, it ruptured. “I was raking leaves out in the yard and, all of a sudden, there was an explosion of pain and my left arm wasn’t responding to my brain,” H. said when I visited him at home [several years ago]. Once the swelling subsided, a neurosurgeon performed a tricky operation to remove the tumor from the spinal cord. The operation was successful, but afterward H. began experienc-

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The operation was successful, but afterward his

left hand felt cartoonishly large—at least twice its actual size.

ing a constellation of strange sensations. His left hand felt cartoonishly large—at least twice its actual size. He developed a constant burning pain along an inch-wide ribbon extending from the left side of his neck all the way down his arm. And an itch crept up and down along the same band, which no amount of scratching would relieve. For eleven years, while the burning was often tolerable during the day, the slightest thing could trigger an excruciating flareup—a cool breeze across the skin, the brush of a shirtsleeve or a bedsheet. “Sometimes I feel that my skin has been flayed and my flesh is exposed, and any touch is just very painful,” he told me. “Sometimes I feel that there’s an ice pick or a wasp sting. Sometimes I feel that I’ve been splattered with hot cooking oil.” For all that, the itch had been harder to endure. H. developed calluses from the incessant scratching. “I find I am choosing itch relief over the pain that I am provoking by satisfying the itch,” he said. He tried all sorts of treatments— medications, acupuncture, herbal remedies, lidocaine injections, electricalstimulation therapy. But nothing really worked, and the condition forced him to retire in 2001. A new scientific understanding of perception has emerged in the past few decades, and it has overturned classical, centuries-long beliefs about how our brains work. We believe that the hardness of a rock, the coldness of an ice cube, the itchiness of a sweater are picked up by our nerve endings, transmitted through the spinal cord like a message through a wire, and decoded by the brain. Our assumption had been that the sensory data we receive from our eyes, ears, nose, fingers, and so on contain all the information that we need for perception, and that perception must work something like a radio. Yet, as scientists set about analyzing the signals, they found them to be radically impoverished. The images in our mind are extraordinarily rich. We can tell if something is liquid or solid, heavy or light, dead or alive. But the information we work from is poor—a distorted, two-dimensional transmission with entire spots missing. So the mind fills in most of the picture. You can get a sense of this from brain-anatomy studies. If visual sensations were primarily received rather than constructed by the brain, you’d expect that most of the fibres going to the brain’s primary visual cortex would come from the retina. Instead, scientists have found that only 20 percent do; 80 percent come downward from regions of the brain governing functions like memory.

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The fallacy of reducing perception to reception is especially clear when it comes to phantom limbs. Doctors have often explained such sensations as a matter of inflamed or frayed nerve endings in the stump sending aberrant signals to the brain. But efforts by surgeons to cut back on the nerve typically produce a brief period of relief followed by a return of the sensation. Moreover, the feelings people experience in their phantom limbs are far too varied and rich to be explained by the random firings of a bruised nerve. People report not just pain but also sensations of sweatiness, heat, texture, and movement in a missing limb. Children have used phantom fingers to count and solve arithmetic problems. The account of perception that’s starting to emerge is what we might call the “brain’s best guess” theory of perception: perception is the brain’s best guess about what is happening in the outside world. The mind integrates scattered, weak, rudimentary signals from a variety of sensory channels, information from past experiences, and hard-wired processes, and produces a sensory experience full of brain-provided color, sound, texture, and meaning. The theory—and a theory is all it is right now—has begun to make sense of some bewildering phenomena. Among them is an experiment that Vilayanur Ramachandran, director of the Center for Brain and Cognition at the University of California, San Diego, performed with volunteers who had phantom pain in an amputated arm. They put their surviving arm through a hole in the side of a box with a mirror inside, so that, peering through the open top, they would see their arm and its mirror image, as if they had two arms. Ramachandran then asked them to move both their intact arm and, in their mind, their phantom arm—to pretend that they were conducting an orchestra, say. The patients had the sense that they had two arms again. Even though they knew it was an illusion, it provided immediate relief. A lot about this phenomenon remains murky, but here’s what the new theory suggests is going on: when your arm is amputated, nerve transmissions are shut off, and the brain’s best guess often seems to be that the arm is still there, but paralyzed, or clenched, or beginning to cramp up. Things can stay like this for years. The mirror box, however, provides the brain with new visual input—however illusory— suggesting motion in the absent arm. The brain has to incorporate the new information into its sensory map of what’s happening. Therefore, it guesses again, and the pain goes away.

THE PAIN OF OUR EXISTENCE

No one needs to remind us how to respond to potentially harmful situations. It’s what keeps us alive.

h

ow the body feels sensations—a brush of fingertips across the hand or the heat from a nearby iron—is complicated. Why the body is capable of sensing, however, is simple: Our survival depends on it. Not only do we need to know what might harm us, we also need to remember how to respond to potentially damaging situations. Fortunately, biology has provided humans and other animals, even the lowliest singlecelled organism, with the perfect

protection mechanism. It is called pain. “Pain is such a fundamental sensation,” says Anne Louise Oaklander, an HMS associate professor of neurology and director of the Nerve Injury Unit at Massachusetts General Hospital, “that rare individuals who are born without pain sensation die, most of them in childhood. For the simplest of our responses to pain, reflex withdrawal, pain neurons tie directly into motor neurons at the spinal cord—without even

going to the brain. We withdraw from pain before we literally know what has hit us.” “Pain signals also tie into learning and memory,” she adds. “We might forget who our fourth-grade teacher was but nobody forgets that hot flames burn. Pain memories are literally seared in.” Thus acute pain, the short, perhaps excruciating, reaction to an environmental cue, works beautifully: it helps keep us alive and unharmed. Pain becomes a problem, however, when its

useful unpleasantness becomes unending. When we experience acute pain, we might yelp, recoil, or exhibit other protective behaviors. In chronic pain, however, these behaviors extinguish and their expression becomes numbed. Yet the horrible insistence of pain—an unrelenting burning sensation, for example, or the torture of continually tensed muscles— remains distressingly alive. Unraveling the neurologic basis for chronic pain drives the investigations of many neuroscientists, including Oaklander. Her research has yielded insights into its causes and has provided some paths toward its better diagnosis and treatment. One of the areas in which Oaklander and others have helped provide clarity is in our understanding of the characteristics and operations of nociceptors, the pain-registering nerve cells in the skin. When damaged by direct trauma, inflammation, or other insult, these sensitive sentinels can misfire, causing scrambled, unfocused messages to bombard the brain, or they can even become stuck in an “on” position, eventually burning out to create numbness or the loss of sensation. Such damage leads to hypersensitivity and chronic pain, which, over time, can actually alter the brain’s wiring. Proper diagnosis becomes critical to stemming this cascade of effects. Yet nociceptors are difficult to observe. These nerves are the merest of threads, so spare that they do not even carry the myelin coat that often wraps nerve cells and speeds their messages. To determine damage to neurons, physicians traditionally have turned to such accepted nerve-function tests as electromyography and nerve conduction. But Oaklander points out that these tests

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FOCAL POINTS Tai Chi practitioners can train their

Pressure Points

fingertips to be more sensitive to touch

a

light touch may be key to alleviating the suffering of people with chronic pain, according to a therapeutic model developed by a team of researchers at Harvard Medical School and the Massachusetts Institute of Technology. Catherine Kerr, an instructor in medicine at Beth Israel Deaconess Medical Center, and colleagues assessed the literature on such touchhealing therapies as Reiki and therapeutic touch as well as mindfulness meditation and found that signature elements of these practices are also important to mechanisms for sensory reorganization in the brain. The researchers speculate that the repeated tactile stimulation administered during touch healing can help guide attention away

from pain, reduce stress, and deemphasize the expectation of pain associated with certain behaviors. Taken together, these outcomes may allow the brain to rewire the “maladaptive” cortical connections formed in response to unremitting pain. In addition, touch healing may play a preventive role by teaching its practitioners how to avoid establishing the neural connections that can make pain endless. Kerr also looked more closely at the ability of individuals to train their brains to control body sensations in a study of Tai Chi practitioners. Tai Chi, a Chinese slow-motion meditative exercise, fosters body awareness by teaching its practitioners to focus on the movements and sensations of their bodies. In neurological terms, such concentration

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places an “attentional spotlight” on the body and its position and contributes to complex motor learning. But Kerr wondered whether Tai Chi also teaches its practitioners to feel sensations more distinctly, a form of perceptual learning. So Kerr assembled a small group of skilled practitioners who undertook a practice regimen designed to encourage them to focus their attention on their extremities, particularly their fingertips. After several weeks of practice, Kerr measured the tactile acuity of members of the study group and compared their results with those of matched controls. She found that the practitioners had improved their ability to accurately sense the subtleties of a surface with their fingertips, and that this enhanced tactile acuity

The Inner Eye

During his first five years of life, light and dark helped him navigate his world. Then his blindness became complete. Yet as a child, Esref Armagan filled solitary hours by drawing, using touch to capture the external world, then re-creating those mental images in the sand, his fingers tracing the edges to ensure the pictures conformed to those in his brain. Today, he creates detailed images that rival the realism of many sighted artists. By first using touch to capture the contours of his subject, Armagan renders the resulting mental representations onto paper fixed to a rubberized tablet, his fingers following—and being guided by—the depressions made by his pencil, allowing him to compare the created image with the one built in his brain. To investigate how this artist’s brain constructs a world built from touch alone, Alvaro Pascual-Leone, an HMS professor of neurology at Beth Israel Deaconess Medical Center, and an international team of colleagues turned to functional magnetic resonance imaging. They found that during drawing, the frontal and parietal regions of Armagan’s cortex became active. This finding was expected; the frontal–parietal area is thought to transform perception into two-dimensional imagery and to help coordinate the sensory and motor information needed for drawing in

DIGITAL CONNECTIONS

Touch can reshape the brain’s connections, helping it interpret what might be lost to other senses

a

sk Alvardo Pascual-Leone what touch is and you likely will get a nice, concise definition, albeit one that starts with a captivating caveat. “We’re tempted to think that touch, like the other senses, is a specialization of our nervous system that allows us to capture different aspects of reality,” says Pascual-Leone, an HMS professor of neurology at Beth Israel Deaconess Medical Center. “For touch, this would include such components as pain, pressure, and temperature.” Then Pascual-Leone throws in a little surprise. “But from our work in nonsighted and temporarily nonsighted people,” he adds, “we have found that this definition doesn’t allow us to fully appreciate the role of touch in brain development. For when we see, hear, smell, and taste, our mind’s fingers touch our mind’s eyes, ears, nose, or tongue. Touch connections shape the way we interpret other sensations.” Pascual-Leone refers here to work his team has done to assess the plasticity of the visual cortex in normally sighted people. Participants in this study first performed a tactile exercise while the researchers monitored the activity in their visual cortexes. Then, for some participants, all visual stimulation was extinguished: For five days and nights, these

participants wore blindfolds that completely blocked all light. During this period, though, all participants went through intensive tactile training that included Braille instruction. After five days, the visual cortexes of the participants were again monitored as they read Braille characters and performed other tactile tests. The researchers found that the blindfolded group had a far greater ability to discriminate Braille characters than did those who had not been blindfolded. This ability diminished within one day, leading the researchers to marvel at the capacity of the visual cortex to reallocate its resources so rapidly to accommodate nonvisual information—and then quickly return to original functioning. “Maybe the visual cortex is visual because we have vision,” says Pascual-Leone. “It may instead be functionally metamodal, capable of processing any other type of information. And perhaps this is true not only of the visual cortex but also of every part of the brain.” Other research by Pascual-Leone’s team, in which they sought to measure the excitability of the visual cortex, underscores this concept. For that study, the researchers first measured how small a flash of light could be and yet remain perceptible to the visual cortex. They determined this minimum level of perception

When a woman who had experienced a blockage to the blood supply to the right portion of her thalamus came to the attention of a group of researchers, the scientists were intrigued. Although the thalamus is recognized as an important relay for sensory information traveling to the cerebral cortex, there have been few explorations of the full role of the midbrain structure. What, the researchers wondered, might a stroke to just one of its two lobes reveal about its function? To try to answer this question, Van Wedeen, an HMS associate professor of radiology at Massachusetts General Hospital, and his colleagues enrolled the woman, a 36-yearold professor, in a long-term study. For six years, they tested her sensory and behavioral responses to light, tones, and mild electrical stimuli while also scanning for changes to her brain. It was about midway through the study that something extraordinary surfaced: The woman reported that she could feel sound. Unlike, say, visual–visual synesthetes, who see letters of the alphabet as particular colors, it is rare to find people with sound–touch synesthesia. Yet the woman was adamant; an array of sounds, including the voice of a radio announcer, elicited “hair-raising” sensations, feelings of pressure, or skin tingling on her left side, the one affected by the lesion. Scans of the woman’s brain showed that while neural pathways between the undamaged lobe of the thalamus and her cortex remained robust, those between the damaged portion and the cortex had become disorganized and may have developed stronger, more direct connections between the auditory and somatosensory regions, leading to the sound–touch synthesia. The

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the senses + one

5 the

How could the patient have heard— and remembered— their conversations when she was clinically dead? by allan j. hamilton

ixth sense By any clinical measure Sarah was dead. Her body had cooled, her heart had stopped, her brain waves had disappeared. During her seventeen minutes as a corpse, a surgical team carefully sealed off her brain during an aneurysm with a titanium clip. In a planned cardiac arrest—cardioplegia— a heart-lung bypass machine replaces the heart’s vital pumping function. Yet with basilar artery aneurysm surgery, all blood flow must stop completely. The period of time the brain can tolerate complete cessations of blood flow can be extended by cooling the brain down. During those seventeen minutes most of the surgical team’s conversation was lighthearted. A nurse recounted her proposal the night before: the ring, the restaurant, the man on bended knee and the waiter who tripped over him and fell into the wine case. The pump was cleared. “Thar she blows, captain.” The bypass machine churned and red blood began to flow again through the

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patient’s tissue. The patient’s body was gently rewarmed. Her heart started beating again. A few minutes later a normal, healthy brain wave pattern reappeared on the EEG. The operation had proceeded flawlessly. As the patient awoke in the intensive care unit, she emerged gradually from the grogginess left by all the anesthetic agents. After several hours, her head cleared. She sat up to greet her surgeon and asked whether something went wrong. “Well, I thought I remembered hearing something ‘blow’ during the case,” she said. “Did the aneurysm blow?” I thought someone said, ‘Thar she blows.’ Like in Moby Dick.” “Yes, well that…what you might have heard…was the tech telling me all the air bubbles were blown clear out of the lines. That’s all.” “Yes, a ring. from Johnston Fellows. Oh… and Morton’s restaurant where someone fell into a wine case.” Sarah’s brain had been dead, without

discernable electrical activity whatsoever: no brain cells had been active, working, firing, or emitting electrical signals. Yet somehow the patient managed to recall the conversation in the operating room while her EEG was flat. She had been, for all intents and purposes, clinically dead yet had somehow managed to encode specific memories of that conversation in the OR. And this was no hazy recollection. She was reproducing practically word for word what had been said. Right down to the a one-and-a-half-carat yellow diamond ring and the stumbling waiter. It would be utterly impossible, from a biochemical, metabolic, or physiologic point of view, for this woman’s brain to create a memory. Yet we also had here unequivocal, scientific evidence that not only was her brain not working, it specifically demonstrated the absence of all cortical electrical activity when these conversations actually took place. And how could such memories survive intact out

in the ether, a place accessible to her brain for later storage only after it revived and awoke? One thing was clear: She had stored and recalled accurate memories of what had happened. One theory held that her brain—and the conscious mind it produced—went somewhere else, beyond its own physical and physiological confines. Out into the cosmos. Another notion, just as radical as the first, was advanced by a group of physics researchers. Their idea was that the memories of the conversations in the OR could survive intact as discrete quanta of energy. No matter how we sought to explain it, this woman’s experience seemed to indicated that the mind, the essential repository of consciousness, could somehow be induced to separate from the very brain that created it. That it could live without neuronal support of any kind. Maybe her “deathlike state” was a prerequisite condition. This is why so many doctors and

researchers now flocked to Scottsdale to see the patient and pore over the records and data. The personnel in the OR were scrupulously and independently interviewed to ensure that no one individual’s recall would become contaminated by hearing the recollections of someone else. The patient was also interviewed and videotaped separately. All OR personnel were asked not to see the patient. The patient became the equivalent of a valuable archeological find. We wanted to leave the site undisturbed. We began our inquiry with a vague, almost smug, scientific curiosity. We felt confident we’d find a plausible explanation that would make this seeming mystery disappear. As the more rational explanations faded away one by one, we began to wonder if maybe we had encountered something unique. Wondrous even. Could we be looking at the neurophysiologic equivalent of the Holy Grail? Were we holding solid, convincing evidence that consciousness could exist wholly separate from the brain? It would be equivalent to stumbling upon a lightbulb (consciousness) that could stay illuminated without any electricity (the brain). “Because I think there was a curl of blonde hair showing. Sticking out. Like it had fallen out. Onto her forehead.” As I quizzed her for further details, it was obvious she had an image of everyone in the operating room. There were so many little facets that she knew. For example, she was able to tell me exactly where the heart-lung bypass was located in the suite. Yet it had only been brought in after she was under general anesthesia for more than two hours. Sarah also knew the pump technician had a beard. She told me the second scrub nurse was African American and very tall. In fact, she was over six feet tall. What emerged from the several conversations I had with Sarah over the next two days was that she was aware of the room, its occupants, and the conversations that took place within it. Her consciousness was present in the operating theater even though it was not supported in any way by her brain. I’m reminded of a carved angel that lies closes to the top of the spire of the Norte Dame cathedral in Paris. She is turning

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ASSEMBLY INSTRUCTIONS HOW TO BUILD A BETTER DOCTOR

FIRST, THE DISCLAIMER. Harvard Medical School— and medical schools around the world—have been making great doctors for decades, even centuries. But as the world of medicine continues to evolve, today’s doctors must be able to respond nimbly to its rapid transformations. To respond to the speed of these revolutions, earlier this decade the School overhauled its curriculum for the first time in nearly a generation. The previous overhaul, the New Pathway of the mid-1980s, had wrought major changes in the first two years of medical education, with a tutorial-centered, case-based program replacing the lecture-heavy curriculum. The latest reform—the New Integrated Curriculum—has sought to better mesh what’s taught in the classroom with what’s taught in the hospitals. The first class to go through the entire New Integrated Curriculum will graduate this spring. This year, too, marks the 100th anniversary of the landmark Flexner Report, which transformed medical education in this country. To commemorate both milestones, we offer assembly instructions for constructing doctors well matched for today’s medicine.

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1

2

Build a better teacher.

3

Through the Academy, the School has assembled best teaching practices and a series of rewards for the best teachers.

In the old HMS curriculum, courses were like silos—self-contained, standalone structures. In fact, many have natural overlaps that the curriculum failed to stress. “Students would complain,” says Richard Schwartzstein, “‘Gee, what you’re covering, we covered in the last course. This is redundant. Don’t you guys ever talk to each other?’” Those discussions have taken place, and now a morning presentation on the changes in respiratory and lung physiology, for example, is followed in the afternoon by one on a drug-resistant tuberculosis epidemic in Russia.

Start with the best ingredients. The step of choosing excellent medical school candidates can neither be overlooked nor overstated. HMS admissions follows a simple formula of seeking aptitude and attitude, idealism and intellectual curiosity.

6

Integrate the material students learn in their clerkships. The Principal Clinical Experience, the School’s reformed clerkship, places students in one hospital for the entire year as they study all the specialties. This interdisciplinary, longitudinal experience allows them to work with the same patients and to witness those patients’ illnesses in various stages. A study of students undertaking the first such clerkship—at Cambridge Hospital—did at least as well, if not better, on Harvard and national board measures of knowledge and skills. Perhaps more notably, compared to their peers in traditional clerkships, students in integrated clerkships reported more confidence in their clinical skills, more satisfaction with

4 5

Help students understand issues of health care delivery.

Integrate the material.

Nurture in students a recognition of the centrality of patients. Francis Peabody, Class of 1907, said it best: “The secret of the care of the patient is in caring for the patient.” Teach students how to listen to patients. Help them understand that patients’ words often contain the clues for unlocking diagnoses.

Raise in them a consciousness that everything from doctors’ biases to the way health care is financed has a direct effect on how, or even whether, patients receive care. Tutorials at HMS now introduce students to the concept of culturally competent care; they address the concern that preconceived notions about a patient’s race, class, age, sexual orientation, or even health habits can skew the care that doctors deliver.

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SMART SCIENCE THE FUTURE OF MEDICINE IS NOW

Smart Clothing First, the disclaimer. Harvard Medical School— and medical schools around the world—have been making great doctors for decades, even centuries. But as the world of medicine School overhauled its curriculum for the first time in nearly a

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A. Helping Hands D

Improving the functioning of a patient’s hands and upper limbs following stroke or other neurological insult is the goal of ongoing research in the laboratory of Paolo Bonato, director of the Motion Analysis Laboratory in the Department of Physical Medicine and Rehabilitation at Spaulding Rehabilitation Hospital. Although such patients can improve movement in their arms and hands by performing tasks that involve reaching for, grasping, and retrieving objects, it can be difficult to ensure a patient practices these movements repeatedly and correctly. So Bonato and his team developed a sensorized glove that tracks hand movements and, when combined with a robotics platform, guides a patient in the therapeutic exercises designed to rebuild function.

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B. Good Vibrations Is it easier to stay upright if the ground beneath your feet moves a bit? It may be for older people, says James Collins, an HMS lecturer on physical medicine and rehabilitation at Spaulding Rehabilitation Hospital, especially people whose peripheral nerves are less keen because of diabetic neuropathy or stroke. Collins, who explores how mild vibratory “noise” can stimulate the peripheral nervous system, tested whether vibrating insoles applied directly to the sole of the foot could help elderly victims of these disorders maintain their balance while standing quietly. Sole-based noise did the trick, piquing the interest of nerves enough to decrease postural sway—even among healthy elderly participants serving as controls.

C. Little Leggings

2 harvard medicine ~ spring 2010

The vision of a skin, a second skin, that embraces a leg and directs its damaged nervous system to learn to function better powers the research of Eugene Goldfield, an HMS assistant professor of psychology at Children’s Hospital Boston and an associate faculty at the Wyss Institute for Biologically Inspired Engineering. As Goldfield envisions it, this skin will serve as a new type of orthotic, one designed to aid brain-injured infants. Conceived of as a soft, light fabric studded with tiny, programmable sensors that can sense a limb’s attempts at movement, Goldfield’s smart garment would take the motion information and feed it to the sensors, which would in turn boost the efforts by the baby’s muscles. By allowing the muscles to experience proper mechanics, the second skin may help rewire an infant’s developing brain, establishing connections—and improving baby locomotion.

D.Dancing Shoes Outfitted with such travel aids as gyroscopes and accelerometers, the GaitShoe aims to help the elderly and people suffering from Parkinson’s disease remain upright and on the straight and narrow, say its developers. Designed by a research team from Massachusetts General Hospital and Massachusetts Institute of Technology, the footgear links the on-board orientation instruments to insoleembedded pressure sensors. The sensors in turn connect with wireless telemetry that transmits vital postural data to remote computers. The shoe–sensor system combination, says Donna Moxley Scarborough, a physical therapist at the hospital and a member of the research team, allows wearers to roam well beyond the confines of a testing laboratory yet remain monitored. And feedback to

GaitShoe wearers can be unconventional: one model being developed for Parkinson’s patients provides musical prompts, helping to set a walking tempo that researchers hope will, through biofeedback, help the patient become more sure-footed.

E. Tell-Tale Threads Using sensors threaded throughout clothing to track the well being of people with stroke, chronic obstructive pulmonary disease, and Parkinson’s disease is a core research goal of a team led by Paolo Bonato, director of the Motion Analysis Laboratory in the Department of Physical Medicine and Rehabilitation at Spaulding Rehabilitation Hospital. “In designing wearable technologies, we always start with the specific challenges of the clinical problem,” says Bonato, “such as

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Five Questions for Michael Greenberg THE COMING REVOLUTION This has been called the century of the brain. How accurate is that moniker? Very. We’re going to see an explosion of advances in neurobiology much as we did with cancer biology in the past few decades. [expand] A key to the department’s future lies in its past: One of the most profound discoveries in the twentieth century in neuroscience was the work of David Hubel and Torsten Wiesel, who showed, in the visual system, that experience plays a key role in brain development. It’s our interaction with the environment that shapes the development and function of the nervous system.

What role will your department play in that revolution?

Name: Michael Greenberg Title: Chair of the Department of Neurobiology, Harvard Medical School Quote: We’re going to see an explosion of advances in neurobiology much as we did with cancer biology in the past few decades. A key to the department’s future lies in its past.

56 harvard medicine ~ spring 2010

A key to the department’s future lies in its past: One of the most profound discoveries in the twentieth century in neuroscience was the work of David Hubel and Torsten Wiesel, who showed, in the visual system, that experience plays a key role in brain development. It’s our interaction with the environment that shapes the development and function of the nervous system. A key to the department’s future lies in its past: One of the most profound discoveries in the twentieth century in neuroscience was the work of David Hubel and Torsten Wiesel, who showed, in the visual system, that experience plays a key role in brain development. It’s our interaction with the environment that shapes the development and function of the nervous system.

How does your own research fit in with that tradition? One focus of our research is Rett Syndrome, a neurological disorder on the autism spectrum that results in human cognitive dysfunction. A number of years ago I was at a Rett Syndrome Society meeting, where I met a family with identical twin girls. One of the sisters, a high school student, sat through the meeting and listened

attentively; her identical twin sister is mentally disabled. She is wheelchair-bound, suffers from severe seizures, and can’t speak a word. [expand] A key to the department’s future lies in its past: One of the most profound discoveries in the twentieth century in neuroscience was the work of David Hubel and Torsten Wiesel, who showed, in the visual system, that experience plays a key role in brain development. It’s our interaction with the environment that shapes the development and function of the nervous system.

What are the most compelling challenges facing the neurobiology field? A key to the department’s future lies in its past: One of the most profound discoveries in the twentieth century in neuroscience was the work of David Hubel and Torsten Wiesel, who showed, in the visual system, that experience plays a key role in brain development. It’s our interaction with the environment that shapes the development and function of the nervous system. A key to the department’s future lies in its past: One of the most profound discoveries in the twentieth century in neuroscience was the work of David Hubel and Torsten Wiesel, who showed, in the visual system, that experience plays a key role in brain development. It’s our interaction with the environment that shapes the development and function of the nervous system.

What recent discovery or innovation in your field excites you the most? A key to the department’s future lies in its past: One of the most profound discoveries in the twentieth century in neuroscience was the work of David Hubel and Torsten Wiesel, who showed, in the visual system, that experience plays a key role in brain development. It’s our interaction with the environment that shapes the development and function of the nervous system. A key to the department’s future lies


CONNECT THE DOCS THE COMMUNITY OF HMS ALUMNI

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THAT OLD SONG AND DANCE

The Second Year Show showcases at the same time it skewers

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hile working at a remote clinic, HMS’s resident humanitarian Paul Farmer learns some astounding news: his longtime partner in health, Jim Yong Kim, has just been named president of Dartmouth College. In other words, HMS’s dynamic duo is breaking up. In the 103rd annual Second Year Show, “Mountains Beyond Brokeback Mountains: The Quest of Dr. Paul Farmer to Find a New Jim Kim and Save Our Nation’s Healthcare,” Farmer initially finds it a struggle to go solo. In his despair, he has too much to drink and calls President Obama and makes some recommendations on healthcare reform that go against his life’s work—reforms so contrary to

his values that they earn the support of Glenn Beck and Sarah Palin. But who better to save healthcare than Paul Farmer? Soon, he pulls himself together and assembles a team to reverse the damage. “Mountains” showcased the Class of 2012’s vocal talents with spot-on renditions of “Total Eclipse of the Heart” and “Man in the Mirror.” The show also included finely executed dance numbers, the highlight of which was a spoof on “Cell Block Tango,” from the musical Chicago. Though the choreography was far from flashy, the performers’ impeccable comic timing made the number the most memorable of the show. The students’ dedication to the writing and rehearsing of

Last fall, Bobby Satcher ’90 performed two joint replacements. That’s just another day in the operating room for most orthopedic surgeons, but Satcher’s “patient”—the International Space Station—was anything but ordinary. An assistant professor of orthopedic surgery at the Northwestern University Feinberg School of Medicine, Satcher is also an astronaut with NASA. As part of his first mission in space last November, he spent eleven days aboard the space shuttle Atlantis, repairing robotic hands, installing new antennas, and helping oversee various experiments on the effects of space on health. In addition to a beloved NBA All-Star jersey, Satcher brought an HMS flag into space as one of his allotted personal items. He will present the flag—signed by his fellow Atlantis astronauts— at the School on Alumni Day, May 28. Bobby Satcher

harvard medicine ~ spring 2010 57


Class Notes Billy Collum “I’m still working two days a week, although I’m undecided about how much longer I’ll continue. I’m also still married to the same lovely woman after 54 years. My extracurricular activities are becoming more limited, but the enthusiasm still persists.”

James Morton “I am alive and well so far, although the economy in our area (California) is very bad. We have an 18 percent unemployment rate and many businesses have failed.”

1944 Edmund Meadows “Approaching 90. If the best is yet to come, I wish it would get here!”

1945 Guilio D’Angio

“Our class now has a Facebook page, which I hope many of you will join. Gerry Foster and Tor Richter will approve your membership.”

1952 D. Kay Clawson

1955 John Laszlo “Looking forward to our 55th class reunion! Is it really possible?”

1956

“My wife, Dr. Audrey Evans, retired last year after more than 50 years of patient care and research in pediatric oncology. I continue lecturing and writing and hold a weekly tutorial with trainees in pediatric oncology.”

“I’m still working at the University of Kentucky College of Medicine as a consultant to the dean. I am on the admission committee for MD, BS/MD, and MD/PhD applicants and am working to increase diversity within medicine.”

1947

1953

1957

Garth Graham

Granville Coggs

George Hill

“Those of us from the Class of 1947 now need the kind of care we were taught at HMS to provide.”

“On August 2, I won the seventh-place ribbon in the men’s 400-meter run (80-to-84 age group) at the 2009 National Senior Games track meet.”

continues to lccture, write, and work with nonprofit organizations. His next book, which will be published this year, is the story of his ancestor, John Saxe, a Loyalist in the Revolutionary War. His book on Thomas Edison will be reprinted next year in paperback. His

1951 Alfred Skinner

1954

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R. W. Chamberlin “Have been working on health care reform, pushing the singlepayer approach. We have sold our place in New Hampshire and are becoming permanent Floridians.”

other books are on Amazon.com and www.georgejhill.com. His wife, Helene (an HMS Fellow in Microbiology from 1964 to 1966), enjoys teaching, conducting research,and mentoring students at the New Jersey Medical School. She is still on the boards of the American Society of Photobiology and the National Society of Colonial Dames in New Jersey.

Richard Wagman “We had a wonderful trip around the Black Sea in late September. It’s a fascinating part of the world. I had my second hip replacement in October and am now back to work.”

1961 Robert Flescher “I am still only mostly retired. I work one day a week in Hartford Hospital’s GI clinic.”

1964 Jay Jackman “In November, my wife Myra and I got together with Steve Hulley, Steve Schroeder, Nancy Kaltreider, and their spouses at the Hulley home in Muir Beach, California. It was a warm and splendid evening that allowed us to continue discussions begun at our 45th reunion last year.”

Douglas Zipes “I recently published my first novel, a medical thriller called The Black Widows.”

1966 Joel Friedman “I still love what I do and am working about 85 percent full time. My wife Carol and I enjoyed playing golf with Jane and Mike Marmor recently.”

Michael Marmor “My wife, Jane (Breeden) ’66, and I remain in California. She is retired but still active in radiation oncology. I continue as a full-time faculty member in ophthalmology at Stanford University, where I am blending

my long-standing interest in the retina and vision with explorations into the world of art. My latest book, The Artist’s Eye, discusses the role of vision and eye disease in the history of art.”

1969 Leonard Altman “In May 2009, my son Jonathan graduated from Harvard Business School as a Baker Scholar, another son Matthew, graduated from HMS, and my daughter Katherine graduated from Stanford (undergraduate). Katherine’s women’s crew team also won the NCAA title last year.”

Michael Harrison

was named to the Institute of Medicine last fall. He also recently received a special grant from the U.S. Food and Drug Administration—one of three awarded annually—to oversee a new Pediatric Device Consortium at the University of California, San Francisco, where he is professor emeritus of clinical surgery and pediatrics.

1970

1971 David Crofoot

Alan Pearlman “I am finishing my second year as editor-in-chief of the Journal of the American Society of Echocardiology. It has been a lot of fun—and a lot of work!”

David Wyler

“I’m working part time in longterm acute care of patients with infectious diseases and am greatly enjoying my semiretirement. I now have the time to catch up on so many areas outside of medicine, including sailing. Best of all, I have more time with my kids!”

“I only do sit-down surgery four days a week now. It pays my overhead and keeps me engaged.”

Stuart Orkin received the 2009 Mentor Award for Basic Science from the American Society of Hematology in December. He is currently the David G. Nathan Professor of Pediatrics at HMS and Children’s Hospital Boston.

1973 Howard Freedman “I’m enjoying my ninth year of retirement, sailing in the Pacific Northwest and the Caribbean, and volunteering at the free Lions eye clinic here in Florida. I’m not playing enough golf, though—too busy.”

1979

Phil Zimmerman

Eve Higginbotham

“We had another fine reunion last June. My youngest son is entering a medical residency and is planning an infectious diseases fellowship.”

became senior vice president and dean for health sciences at Howard University in Washington, DC, in January. An ophthalmologist, she was

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Obituaries

Class Notes previously dean and senior vice president for academic affairs at Morehouse School of Medicine in Atlanta, Georgia.

1981 Alan Guttmacher was named acting director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, which is part of the National Institutes of Health. He was previously director of the Vermont Regional Genetics Center and Pregnancy Risk Information Service at the University of Vermont.

Richard Stone “Harvard Medical School’s standards must be declining. I was recently promoted to Professor of Medicine. Persistence plays a role: I started at HMS 36 years ago and haven’t left. I continue to do clinical/translational research on leukemia, tryng to cure more adults with this terrible disease.”

1982 Aaron Appiah “I’m still practicing vitreoretinal surgery in Tallahassee, Florida. It’s hard to believe that nearly three decades have elapsed since medical school.”

Paul Okunieff was named director of the University of Florida Shands Cancer Center and chairman of the University of Florida College of Medicine’s Department of Radiation Oncology. He was previously the Philip Rubin

professor in radiation oncology and chair of the Department of Radiation Oncology at the University of Rochester School of Medicine and Dentistry in New York.

1935 S. Halcuit Moore, Jr.

1983 Hugh Calkins was recently named the inaugural recipient of the Nicholas J. Fortuin Professorship of Cardiology at Johns Hopkins School of Medicine.

William Ericson was awarded the Jules Tinel, MD Award by the Association of Extremity Nerve Surgeons at their annual symposium in 2009. The award recognizes work that promotes the scientific advancement of knowledge regarding peripheral nerve disorders.

Sloan–Kettering Cancer Center honors scientists under age 46. Meyerson is an associate professor of pathology at HMS and the Dana–Farber Cancer Institute.

Exeter, New Hampshire.”

1994 Atul Gawande

was recently named one of America’s Best Leaders by U.S. News & World Report. She has been president of Echoing Green, an organization that invests in and supports outstanding emerging social entrepreneurs, since 2002.

was named a 2009 Fellow of The Hastings Institute, a nonprofit bioethics research institution. He is currently an associate professor of surgery at HMS, an associate professor in the Department of Health Policy and Management at the Harvard School of Public Health, and research director for the Center for Surgery and Public Health at Brigham and Women’s Hospital.

1992

2002

Philip Starr

Gary Proulx

Eric Fynn-Thompson

“My wife, Chantal, and I welcomed our baby boy, Major Wei-Qi Starr, on April 27, 2009.”

“I recently left my positions as chairman of radiation oncology and medical director of the cancer center at Guthrie Health in New York and Pennsylvania. I have rejoined the staff at Massachusetts General Hospital in the Department of Radiation Oncology and am also the medical director of radiation oncology at Exeter Hospital in

has joined the Department of Surgery, Plastic and Reconstructive Surgery at Pottstown Medical Center in Pottstown, Pennsylvania.

1987 Louis Aviles is enjoying his fourth year of solo practice in gastroenterology. He has two children in college and one in high school.

1989 Matthew Meyerson was one of three investigators to receive the 2009 Paul Marks Prize for Cancer Research. The $50,000 award from Memorial

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1991 Cheryl Dorsey

Died April 23, 2009, at the age of 98, in Dallas, Texas. Moore was a pediatrician and pioneer in Dallas’s early clinics for congenital syphilis and childhood tuberculosis. Between 1946 and 1955, during his tenure as chief of premature units at Bradford and Parkland Memorial hospitals, the mortality rate among premature infants dropped from 46 to 16 percent. Moore practiced pediatrics at the Dallas Medical and Surgical Clinic until his retirement in 1986. He was also chief of staff at that city’s Children’s Medical Center, a pediatric consultant to the Head Start Program of Dallas, and a faculty member at the University of Texas Southwestern Medical Center. Moore is survived by his partner and companion, Mary Lee Casey; his children, Terry, Alan, Carol Martin, and Nancy Hopkins; and eight grandchildren.

1938 Robert Tucker, Jr. Died April 27, 2009, at the age of 94, in Atlanta, Georgia. Following graduation, Tucker did surgical residencies at Massachusetts General Hospital and other Boston hospitals. He worked as a flight surgeon for Pan American Airways, Ltd., helped establish hospitals in Africa, and later saw service in North Africa, Sicily, Italy, and the Pacific. With the U.S. Marine Corps, he was among the first team of American doctors to view the effects of atomic bombs

dropped in Japan. In 1947, Tucker opened a medical practice in East Point, Georgia, which for many years was open 24 hours a day. He was a staunch advocate of a healthy lifestyle and created “The Tucker Method,” which provided easily understood guidance about the relationship between diet and health. Tucker is survived by his wife of 56 years, Marion; his children, Robert III, Suzanne Plybon, and Richard; and eight grandchildren.

1942 Don W. Fawcett Died May 7, 2009, at the age of 92, in Montana. Fawcett was commissioned as a captain in the U.S. Army Medical Corps and served as a battalion surgeon in the European Theater during World War II. In 1946 he became a research fellow in anatomy at HMS, where he rose to the rank of assistant professor of anatomy before assuming the position of chairman of the Department of Anatomy at Cornell Medical School in 1955. He returned to HMS four years later as chairman of the Department of Anatomy and the Hersey and James Stillman professor of comparative anatomy. He also served HMS as senior associate dean for preclinical sciences from 1975 to 1977. Fawcett was a pioneer in the use of the electron microscope in the early 1950s and was widely published on cell biology. Fawcett was a cofounder and first president of the American Society for Cell Biology. After retiring from HMS in 1981, he was a senior research scientist and director of electron

microscopy at the International Laboratory for Research on Animal Diseases in Nairobi, Kenya. Fawcett is survived by his wife of 68 years, Dorothy; his sons, Bob and Joe; two daughters, Mary Papish and Dona Boggs; thirteen grandchildren; and ten great-grandchildren.

1943 [A or B?] John W. Finley Died July 6, 2009, at the age of 90, in Stanwood, Washington. Finley served with the U.S. Army in the European Theater until 1947, when he settled in Seattle, Washington. He practiced medicine in that area until his retirement in 1988. Finley was predeceased by his first wife, Leona, and a son, John (“Bill”), Jr. He is survived by his second wife, Barbara; his children, Michael, Anne, Judy Russell, and Marnell Olson; and his stepchildren, Frank, Mark, Paul, Kurt, Glen, and Tekla VanderWel.

1943 [A or B?] John C. Nemiah Died May 11, 2009, at the age of 90, in Nashua, New Hampshire. Nemiah served in the U.S. Army Medical Corps during World War II before working as a psychiatrist and psychoanalyst, first at Massachusetts General Hospital and later at Beth Israel Hospital in Boston, where he was psychiatrist-in-chief. He was also a professor of psychiatry at HMS before retiring from both positions in 1985. He continued to teach psychiatric residents at Mary Hitchcock

Memorial Hospital in Lebanon, New Hampshire. Nemiah’s research interests included anxiety disorders, dissociative conditions, alexithymia, and psychosomatic medicine. He had also been editor of the American Journal of Psychiatry. Nemiah was predeceased by his first wife, Muriel, and by his second wife, Margarete. He is survived by a daughter, Ann Conway; two sons, James and David; a stepdaughter, Elaine Cohen; and eight grandchildren.

1943 [A or B?] I. Herbert Scheinberg Died April 4, 2009, at the age of 89, in Elizabethtown, New York, following a long illness. Scheinberg served in the U.S. Army Medical Corps during World War II. From 1955 to 1992 he was a professor of medicine at the Albert Einstein College of Medicine in the Bronx, New York, where he was also head of the Department of Genetic Medicine from 1973 to 1992. Scheinberg devoted most of his career to the study and treatment of Wilson’s disease, a hereditary neurological disorder. As a result of the diagnostic tests and treatments he and his staff perfected, patients with the disease are now able to survive the once-fatal disease. He is survived by his wife of 52 years, Denise; daughters, Anne and Cynthia; son, David; and four grandchildren.

1945 Harry C. Bishop

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Obituaries Died May 4, 2009, at the age of 88, in Haverford, Pennsylvania. Bishop served in the U.S. Army Medical Corps and was the chief pediatric surgical resident at Children’s Hospital Boston before he was recruited to the Children’s Hospital of Philadelphia in 1954 by C. Everett Koop, who was then surgeon-in-chief there. Together they pioneered the Bishop–Koop procedure, used to treat intestinal obstruction in babies with cystic fibrosis. In 1966, Bishop was part of a team that cared for a baby girl born without an intestine. Their groundbreaking work proved for the first time that human infants could survive and grow on hyperalimentation, a form of intravenous feeding. Bishop was also a professor of surgery at the University of Pennsylvania School of Medicine. He retired from both positions in 1991. Bishop is survived by his wife, Deborah,; three children, Robert, Thomas, and Katherine Kilmurray; three stepchildren, William, Daisy, and Noel Newbold; and four grandchildren.

1945 Milton Clay Ragsdale, III Died May 25, 2009, at the age of 88, in Homesdale, Alabama. After serving as a captain in the U.S. Army, he practiced radiology in Birmingham, Alabama, for more than 40 years. Ragsdale is survived by his wife of 57 years, Jean; his three children, Laurie Yearout, Jeanie Thomas, and M. Clay, IV; and seven grandchildren.

1946

Jeremiah Mead Died July 4, 2009, at the age of 88, in Ellsworth, Maine. Mead did his internship and residency at Boston City Hospital before spending two years conducting research in cold weather physiology for the Quartermaster Corps of the U.S. Army at a research station in Hudson’s Bay, Canada. This experience sparked his lifelong interest in physiology research, which he continued as a faculty member at the Harvard School of Public Health. He retired from his position as Philip Drinker Professor of Environmental Physiology there in 1987. He is survived by his wife of almost 64 years, Dorothea; three sons, Jeremiah, Warren, and Andrew; a daughter, Sarah; nine grandchildren; and three step-grandchildren.

1947 John M. “Mac” Olney, Jr. Died April 2, 2009, at the age of 85, in Santa Rosa, California, of Alzheimer’s disease. Olney served in the U.S. Navy while finishing his medical degree. He completed his residency in surgery at Brigham and Women’s Hospital, which was interrupted by his service with the 8209th MASH unit in Korea. During his training he researched the use of flame photometry to measure potassium levels in blood, a major advancement in patient care. In 1957, he opened a surgical practice in Santa Rosa. Olney was active in several professional organizations including the American College of Surgeons and was an early advocate of breast-sparing surgery for the treatment of breast cancer. Olney is survived by his wife of 54 years, Pauline; five children,

62 harvard medicine ~ spring 2010

Mary, John, Elizabeth Beck, Robert, and Douglas; and nine grandchildren.

1948 Loren A. Gothberg Died July 19, 2009, at the age of 89, in Spokane, Washington. Gothberg served in the U.S. Army for four years during World War II and for another two years as a medical officer in the Far East command during the Korean War. He did his residency at St. Luke’s Hospital in Chicago, Illinois, Deaconess Hospital in Spokane, and the University of Washington School of Medicine in Seattle. In 1954 he opened an internal medicine practice in Spokane, focusing on the treatment of acute and chronic kidney failure. He pioneered the use of peritoneal dialysis in Spokane and in 1962 cofounded the Spokane Artificial Kidney Center. Gothberg was an associate clinical professor of medicine at the University of Washington, was director of medical education at St. Luke’s Hospital, and was on the faculties of the Spokane Family Medicine and Spokane Internal Medicine programs. He also served on the staff of Deaconess and Sacred Heart hospitals. For several years following retirement he was the medical director for North Coast Life Insurance Co. Gothberg was predeceased by his wife of 56 years, Eleanor. He is survived by his son, John; daughter, Karen; foster daughter, Chhany Humphry; seven grandchildren; and eight great-grandchildren.

1949 Stanley W. Daum

Died May 30, 2009, at the age of 86, in Providence, Rhode Island. Daum served in the U.S. Navy as a pharmacist’s mate during World War II. He completed his internship and residency at Boston City Hospital and the Boston Veterans Administration Hospital before serving as a captain in the U.S. Air Force Medical Corps during the Korean War. He was later a staff physician at the McKinney Veterans Administration Hospital in McKinney, Texas, and a clinical instructor for the University of Texas Southwestern Medical School. From 1957 to 1979 he had various roles at the Providence Veterans Administration, including the acting chief of staff. Daum loved teaching and held appointments as assistant clinical professor of medicine at Boston University School of Medicine and as clinical associate professor of medicine in the Brown University Program in Medicine. From 1984 to 1986 he was a consulting physician at the Eunice Kennedy Shriver Center in Taunton, Massachusetts, and eventually became its medical director. Daum is survived by his wife of more than 60 years, Ann; a daughter, Susan; a son, Eric; and one grandchild.

1949 Maurice Noel Levy, Jr. Died May 1, 2009, at the age of 82, in Amarillo, Texas, after a long struggle with complications of diabetes. Levy’s surgical training was interrupted by the Korean War, during which he served in the U.S. Navy as chief medical officer onboard the USNS General William O. Darby. He later joined the Naval Reserve,

achieving the rank of lieutenant commander. Levy completed his surgical training at Boston City Hospital, where he was chief resident in general surgery. He opened a private practice in Bridgeport, Connecticut in 1956 but relocated to Amarillo two years later. There, he worked as chief of surgery at the Veterans Administration Hospital and opened a private practice. He was a member of several professional organizations and also worked at both Northwest Texas and St. Anthony’s hospitals. In the 1970s Levy became a private pilot with instrument, multi-engine, commercial, and air transport ratings. He joined the Military Entrance Processing Station as chief medical officer and remained until his retirement in 1987, after which he continued to teach pilots and perform medical exams for the Federal Aviation Agency. Levy was predeceased by a son, Daniel, in 1964. He is survived by his wife of 59 years, Joan; three children, Noel, Elizabeth, and Andrew; and four grandchildren.

1952 Samuel Kirby Day, Jr. Died May 16, 2009, at the age of 80, in Orange, California. Day interned at Washington University Hospital in St. Louis, Missouri, before beginning a two-year tour of duty with the U.S. Army in Nurnberg, Germany. He later entered into general practice in Santa Ana, California, doing what he loved: caring for patients. He retired in 1988. Day was predeceased by his wife of 50 years, Carolee, in 2003. He is survived by his four children, S. Kirby III, Kimberly Crocker, Kristen Bartley, and

Keith; and three grandchildren.

1952 William S. Rachlin Died April 8, 2009, at the age of 79, in Needham, Massachusetts. Rachlin graduated from Princeton University’s threeyear accelerated program in 1948 before entering HMS at the age of 19. Following his residency in surgery at Beth Israel Hospital in Boston, he received a commission in the U.S. Air Force, during which he served two years as the chief of surgery at Robins Air Force Base in Georgia. He then returned to Boston to start his surgical practice at Beth Israel and became an instructor in surgery at HMS. Rachlin was also chief of surgery at Revere Memorial Hospital and was president of the Norfolk District Medical Society, which named him its 2002 Community Clinician of the Year. Following his retirement in 2000, he became a volunteer science teacher in several local middle schools and also taught courses on scientific and medical subjects at the lifelong learning programs at Brandeis University

1953 William C. Ivins, Jr. Died May 2, 2009, at the age of 82, in Salem, South Carolina. Ivins practiced pediatrics for 37 years at North Shore Medical Group in Huntington, New York. He was predeceased by three step-grandchildren. He is survived by his wife, Cathryn; his daughters, Deborah Taylor, Hannah Narowski, and Sarah; stepsons, Christopher Tyson and Kevin Tyson; five grandchildren; and six step-grandchildren.

1957 Armen Haig Tashjian, Jr.

Amy, and Victoria; and three grandchildren.

1960 Harold M. “Sandy” Trusler. Died April 11, 2009, at the age of 74, in Indianapolis, Indiana. Trusler completed his residency at Indiana University Medical Center and then entered into private practice in plastic surgery with his father. He reduced his practice in 1980 and became director of medical affairs at Blue Cross Blue Shield of Indiana and medical director for the Indiana Medicaid Program. In 1984, he helped develop Key Health Plan and served as its medical director. He was also instrumental in the formation of the Indiana Physicians Insurance Company and was its first president. Trusler left the business sector in 1987 and returned full-time to medicine. He retired from private practice in 1996. Trusler is survived by his wife of 48 years, Kay; son, Marshall; daughters, Lisa and Terri; and seven grandchildren.

Died July 3, 2009, at the age of 77, in Wellesley Hills, Massachusetts. Tashjian was a research fellow at the National Institutes of Health in Bethesda, Maryland, from 1959 to 1961 before becoming a professor of biological chemistry and molecular pharmacology at HMS. He was also a professor of toxicology at the Harvard School of Public Health, where he founded the Department of Molecular and Cellular Leon Eisenberg Toxicology. During the1992–2009 1990s Leonhe Eisenberg, turned histhe attention Maudeto and drug Lillian Presley Kenneth professor Gorelick emeritus of discovery social medicine, and development died on September Died 15, 2009 June 8, at2009, the age at the age of 87. Internationally and became a consultant known in to pediatric psychiatry, 67, at his home Eisenberg in Washington, was among thethe pharmaceutical first to explore industry. autism and itsDC, relationship of brain cancer. to pa-Gorelick tients’ Tashjian families was and a co-author social settings; of he also waspioneered chief of continuing random- medical ized,Principles placebo-controlled of Pharmacology, clinical trials ofeducation novel drug and therapies. vice-chair for Eisenberg a leading wastextbook appointed on chair the of psychiatry the residency at Massachusetts training program General subject. Hospital He was in 1967. a recipient The following of year, at St.prompted Elizabethsby Hospital the and the Astwood Award Luther for basic DC Commission assassination of Martin King, Jr.,the Eisenberg helped on Mental and Regis College. Rachlin was scientific in played skeletala pivotal Health He was also launch the School’s affirmative action discoveries program. He roleServices. in that program, predeceased by hismany wife,outstanding Joy. He biology neuroendocrinology a board certified psychiatrist recruiting African and American and other minority applicants to the is survived by his daughters, of therole Endocrine Society’s in private practice, and had School. Eisenberg also playedand a major in building the Department of Social Medicine Faye and Margo Gray; and two Distinguished Leadership Award. been a clinical instructor at grandchildren. Tashjian is survived by his wife, HMS, and a professor emeritus Carol; his daughters, Elizabeth, of psychiatry at George

1967

harvard medicine ~ spring 2010 63


Taking a History PROFILES OF OUR GRADUATES

Apologize to the Children

Healing Child Abuse Trauma Through Attachment Reconciliation by Gaston Blom ’44 (Larch Press, 2009) Through a series of moving narratives, the author—a child and adolescent psychiatrist—challenges the usual management and treatment approaches to child-abuse trauma. Instead, he explains how elements of restorative justice such as acknowledgment, truth-telling, contrition, apology, repentance, forgiveness, amnesty, and reconciliation are present in the attachment reconciliation treatment process he advocates.

Connected

The Surprising Power of Our Social Networks and How They Shape Our Lives, by Nicholas Christakis ’88 and James Fowler (Little, Brown, 2009) This entertaining book explains why emotions are contagious, how health behaviors spread, and how we find and choose our partners. The authors challenge the notion of the individual and suggest that social networks influence our ideas, emotions, health, relationships, behavior, politics, and more.

ACSM’s Exercise is Medicine A Clinician’s Guide to Exercise Prescription by Steven Jonas ’62 and Edward M. Phillips (Lippincott, Williams and Wilkins, 2009)

The Surgical Hospitalist Program Management Guide Tools and Strategies for Executives and Physicians by John Nelson, MD, and John Maa ’94 (HCPro, 2009) This book and CD set spotlights successful surgical hospitalist programs to show how the experts developed thriving programs with a strong return on investment. The authors provide casestudy profiles of real-life examples and offer comprehensive approaches to build or refine a practice.

Passion, Compassion and Pain The Life of a Maverick Neurosurgeon by Guy Owens ’50 (PublishAmerica, 2008)

Part of the American College of Sports Medicine’s initiative to make physical activity a standard part of disease prevention and treatment, this guide is designed to help physicians motivate patients to exercise. The book covers how to design practical exercise programs for otherwise healthy patients, as well as for those with special conditions like pregnancy, obesity, and cancer.

In this memoir, Owens recounts tales from his childhood and education and shares his philosophy on the control of chronic pain, honed after years of research and patient care. He also addresses the debate over the use of prescription narcotics and invasive surgery.

The End of Overeating

Fasten Your Seatbelt

The author, a former FDA commissioner uncovers the facts behind America’s number-one public health issue: overeating. In this in-depth analysis of the latest research, Kessler examines the food industry, explains why the foods we eat can trigger overindulgence, and offers practical tips on controlling consumption.

Written for the siblings of children with Down syndrome, this easy-to-read guide answers 85 questions culled from interviews with families. The authors address how siblings can manage uncomfortable situations, handle conflicts, and explain Down syndrome to their friends.

Taking Control of the Insatiable American Appetite by David Kessler ’77 (Rodale, 2009)

64 harvard medicine ~ spring 2010

A Crash Course on Down Syndrome for Brothers and Sisters, by Brian G. Skotko ’06 and Susan P. Levine (Woodbine House, 2009)


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