Harvard Medicine magazine, Autumn 2021 by Harvard Medical School

medicine HARVARD

AUTUMN 2021

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a sense of place In spring 1900, the Faculty of Medicine at Harvard, noting the need for a new site for the rapidly growing medical school, purchased a 26-acre parcel in Boston’s Fenway and Mission Hill sections. By 1906, the farmland had given rise to the Quadrangle, five granite and marble buildings boxing a rectangle of green. Besides offering a touch of natural beauty, the green space serves as the School’s front yard, hosting a range of outdoor activities, such as rallies for science, commencement ceremonies, impromptu picnics, and pickup games of flag football, soccer, and Frisbee.

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JOHN SOARES

H A R VA R D M E D I C I N E

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DETAILS: The opening page of

the first volume of Alvise (Luigi) Cornaro’s multivolume work on the benefits of a temperate life boasts this illuminated letter. Itself a story, it ushers readers into Cornaro’s telling of his own story of health and long life.

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contents Autumn 2021

SPECIAL REPORT AGING

DEPARTMENTS

11 An Age-Old Desire

Letters from the dean and our readers

12 When Protection Goes Awry by Charles Schmidt Neuroinflammation is increasingly being implicated in cognitive decline. 18 Melting Point by Stephanie Dutchen When heat intensifies, older adults weaken—but they don’t have to. 20 A Place for Dignity? by Elizabeth Gehrman As a growing number of older adults require care, some worry that respect may be a diminishing resource. 26 A Sadness So Profound by Amanda Loudin

MATTIAS PALUDI (COVER); DISCORSI DELLA VITA SOBRIA (FACING PAGE)

Prolonged grief often goes undiagnosed even though treatment can be pivotal to overall well-being. 30 Life’s Through Line by Ann Marie Menting An interview with the head of the nation’s institute on aging research.

4 Commentaries

6 Discovery Research at Harvard Medical School 10 Noteworthy News from Harvard Medical School 34 Five Questions by Ekaterina Pesheva Caroline Shamu on finding molecular candidates for drugs and therapies 35 BackStory by Dominic Hall An alumnus’ innovations in technique and materials revolutionized surgical care of hip joint diseases

40 Roots by Susan Karcz Hilary Siebens on her system for organizing patient care 41 Student Life by Bobbie Collins and Elizabeth Gehrman Four MMSc graduates on their plans for making a difference in the world

45 Match Day FEATURE 36 The Beckoning Lights on a Distant Shore by Kent Wong A young man braves a watery escape from China and begins a new life as a physician in the United States.

| Volume 94 | Number 3

The residency placements for members of the Class of 2021 49 Rounds Alumni recount their most memorable clinical rotation during medical school

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COMMENTARIES

medicine HARVARD

Ensuring older patients receive competent, compassionate care AMONG THE INITIATIVES OUR STUDENTS LAUNCHED THIS PAST YEAR , the

COVID curriculum, adopted by medical schools worldwide, was a point of pride. This initiative also had an extracurricular component: COVID Community Voices, which paired our students with older adults in the Boston area who, by staying home to avoid the risk of infection, were separated from family and friends and therefore at increased risk for social isolation. Students who took part in this program would regularly call their “phone pals” to check in, talk, and listen. In addition to helping stave off loneliness and fear in members of a vulnerable population, the project gave joy and purpose to our students. COVID Community Voices is still going strong. The percentage of older adults in the United States is growing. In its 2019 American Community Survey, We have launched the U.S. Census Bureau reported that an estimated 54 a curricular effort million people, approximately 16.5 percent of our nation’s that will ensure that population, were over the age of 65. That percentage is all students, no matter expected to climb to 20 percent by 2030, with many their specialty, will be individuals experiencing multiple medical conditions prepared to address and complex psychosocial circumstances. Workforce projections, such as those produced by the American the unique needs of Geriatrics Society, indicate that by 2025, there will be their older patients. approximately 6,000 certified geriatricians in the United States, about fivefold short of the anticipated need. Producing more geriatric specialists is a goal we are working toward through the HMS Multicampus Geriatric Medicine Fellowship Program and other Harvard geriatrics training programs. In addition, we have launched a curricular effort that will ensure that all our medical students, no matter their specialty, will be prepared to provide sensitive and competent care to address the unique needs of their older patients. In 2019, our Educational Policy and Curriculum Committee selected aging population/endof-life care as a required curricular theme, which, together with health equity and disparities, trauma-informed care, substance abuse and pain, and sexual and gender minority medicine, integrate pressing societal issues into our MD curriculum. Co-directors Andrea Wershof Schwartz, an HMS assistant professor of medicine at the VA Medical Center and Brigham and Women’s Hospital, and Kristen Schaefer, MD ’94, an HMS assistant professor of medicine, part-time, at Dana-Farber Cancer Institute, have worked with HMS faculty to integrate geriatric competencies across the pre-clerkship, Principal Clinical Experience, and post-PCE phases of our curriculum. During the pandemic, the curriculum theme co-directors collaborated with students, trainees, and colleagues on research that produced peer-reviewed publications on several topics including clinical geriatrics and our trainees’ adaptation of the “My Life, My Story” program, a tool for getting to know seriously ill and aging patients as people. Our recognition of the need to prepare our students to provide informed care to older adults reflects our tradition for pedagogic leadership and compassionate care. Our students are passionate about becoming skilled caregivers, and our faculty are dedicated to educating them to become physicians who are leaders in medicine.

Editor Ann Marie Menting Design Director Paul DiMattia Associate Editor Susan Karcz Designer Maya Rucinski-Szwec Contributors Bobbie Collins; Stephanie Dutchen; Elizabeth Gehrman; Dominic Hall; Amanda Loudin, Ekaterina Pesheva; Charles Schmidt, Kent Wong Editorial Board JudyAnn Bigby, MD ’77; Emery Brown, MD ’87 PhD ’88; Rafael Campo, MD ’92; Elissa Ely, MD ’87; Timothy G. Ferris, MD ’92; Alice Flaherty, MD ’94; Atul Gawande, MD ’94; Donald Ingber, PhD; Sachin H. Jain, MD ’08; Perri Klass, MD ’86; Jeffrey Macklis, MD ’84; Victoria McEvoy, MD ’75; Barbara McNeil, MD ’66 PhD ’72; Lee Nadler, MD ’73; James J. O’Connell, MD ’82; Nancy E. Oriol, MD ’79; Anthony S. Patton, MD ’58; Mitchell T. Rabkin, MD ’55; Eleanor Shore, MD ’55 Dean of Harvard Medical School George Q. Daley, MD ’91 Executive Dean for Administration Lisa Muto Chief Communications Officer Laura DeCoste Director of Editorial Services Maria Fleming Buckley Harvard Medical Alumni Association Kenneth Bridges, MD ’76, president Tamara Callahan, MD ’95, vice president Oni Blackstock, MD ’05; Douglas Chin, MD ’94 MMSc ’94; David Cohen, MD ’86 PhD ’87; John F. Cramer III, MD ’74; Carmen Davis, MD ’90; Elizabeth Garner, MD ’94; Jessica Ann Holman, MD ’13; Sitaram M. Emani, MD ’97; Margaret Liu, MD ’81; Numa Pompilio Perez Jr., MD ’15; Coleen Sabatini, MD ’04; Nancy Petersmeyer, MD ’80; Nina Tolkoff-Rubin, MD ’68 Chair of Alumni Relations A. W. Karchmer, MD ’64 Harvard Medicine is published two times a year at 25 Shattuck Street, Boston, MA 02115. PUBLISHERS: Harvard Medical Alumni Association

and Harvard Medical School © The President and Fellows of Harvard College PHONE: 617-432-7878 EMAIL: harvardmedicine@hms.harvard.edu MAIL: 107 Ave. Louis Pasteur, Boston, MA 02115 WEB: hms.harvard.edu/magazine

ISSN 2152-9957 | Printed in the U.S.A.

RANDY GLASS

George Q. Daley Dean of Harvard Medical School HARVARD MEDICINE | AU T U M N 202 1

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The experience factor I WAS PLEASED TO READ THE ARTICLE “Field

Corrections” in the Winter 2021 issue of Harvard Medicine. As the article quite properly states, racial and ethnic stereotypes based on past assumptions need to be reevaluated, discarded, or both. The article and its sources indicate that objective measurements based on bioinformatics and machine learning may soon supersede racial and ethnic identity as information to be used in patient assessment and care. The article further indicates that gene sequencing technology may largely replace racial and ethnic identity in the clinical area and become a standard of care. While these ideas are interesting to consider, those Harvard-trained physicians among us with decades of clinical experience will recognize that numerous clinical clues, including race, ethnicity, and socioeconomic status, are commonly of great value in guiding us toward a likely diagnosis in an efficient, prompt, and cost-effective manner. It is still true that the well-trained and experienced physician frequently moves quickly and nearly subconsciously to tentative conclusions that are remarkably accurate, thus allowing for timely investigation and treatment. Thus, Black African ancestry is associated with sickle cell anemia, sarcoidosis, severe primary hypertension, and increased occurrence of type 2 diabetes, prostate cancer, and renal insufficiency. Greek ancestry is associated with beta thalassemia. Hispanic ethnicity is associated with insulin resistance, obesity, metabolic syndrome, and type 2 diabetes. Those of Asian ancestry are prone to osteoporosis. What is rapidly evolving, and what clinicians at all levels need to be acutely cognizant of, is the diminishing association between racial or ethnic identification and socioeconomic status. Low

medicine HARVARD

WINTER 2021

must, therefore, retain a strong component of efficient, seasoned clinical judgment along with technological advances. STEPHEN R. SMITH, MD ’63 BALTIMORE, MARYLAND

To our readers

Confronting Racism in Medicine

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socioeconomic status continues to be related to important conditions, such as protein deficiency, scabies, lice, lead poisoning, domestic trauma, alcoholism, and excessive sodium consumption. However, past associations between lower socioeconomic status and racial or ethnic identity have largely disappeared and must be eliminated, if they still exist, in current assessment processes in all organizations and offices. What is needed going forward is a commonsense combination of technology and clinical expertise, with an awareness of social changes as they occur. Our health care system is overwhelmed with excessive cost already and

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THIS EDITION of Harvard Medicine ushers in a new era in how we deliver you the stories of the students, faculty, and alumni of Harvard Medical School. For nearly a century, this publication and its predecessors have captured the contributions that HMS and its people make to biomedicine, medical education, and health care policy and delivery the world over. And for nearly that entire time, this magazine has been a physical entity delivered to you by mail. Yet, like medicine itself, this magazine has evolved, updating its title over the years and, nearly two decades ago, developing a digital presence. We are now expanding that digital presence and increasing our digital readership. In the coming year, we plan to increase the frequency of new material and present it to you in an online format that will reflect the award-winning quality you have come to expect from our physical issues. Be assured, the physical issue will not disappear. We will continue to print the magazine twice a year, in May and October. But now we will rely on new technologies to bring you more of what is happening at HMS more often. We’re excited about this change—and this opportunity. We hope you will be, too.

Harvard Medicine welcomes letters to the editor. Please send them by mail (Harvard Medicine, 107 Avenue Louis Pasteur, Suite 111, Boston, MA 02115), or by email (harvardmedicine@hms.harvard.edu). Letters may be edited for length or clarity or to conform to HMS style.

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ON CAMPUS

I DISCOVERY AT HARVARD MEDICAL SCHOOL

Birthday Blowout in nearly 3 million households between January and November 2020 suggests birthday gatherings may have helped spread infections during the pandemic. Conducted by health care policy researchers at HMS and the RAND Corporation, the analysis used birth dates drawn from health insurance claims as a proxy measure for the possibility of a celebratory gathering. Infections were 30 percent more likely in households with a birthday within two weeks of a household member’s COVID-19 diagnosis. The link was greater for a child’s birthday. The findings, say the scientists, could inform guidance on limiting informal gatherings should another surge occur. AN ANALYSIS OF INFECTION RATES

Whaley CM et al., JAMA Internal Medicine, June 2021

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HM INDEX: IN 2019, ABOUT

262 MILLION PEOPLE WORLDWIDE WERE DIAGNOSED WITH ASTHMA, AND ABOUT 460,000 DIED OF IT.

Health Care Policy CARDIOLOGY

JULIA RIOS GOMEZ/ISTOCK/GETTY IMAGES (FACING PAGE); ALEXANDER FORD/E+/GETTY IMAGES

Signs of plaque found in low-risk people with HIV SIGNIFICANT AMOUNTS of atherosclerotic plaque have been found in the coronary arteries of people with HIV, even in those considered by traditional measures to be at low-to-moderate risk of future heart disease, according to HMS investigators at Massachusetts General Hospital who were key to coordinating the study. The findings emerged from the global REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) study. Researchers found that the higher-than-expected levels of plaque could not be attributed only to traditional cardiovascular disease risk factors like smoking, hypertension, and lipids in the blood, but were independently related to increased arterial inflammation and immune system activation. Cardiovascular disease is occurring among people with HIV at approximately twice the rate for people without the disease. The findings provide useful insights that may inform further studies to identify effective plaque reduction or prevention strategies, such as the possible use of statin medicines, for this patient population. REPRIEVE is the largest study of cardiovascular disease among people living with HIV, having enrolled 7,700 participants at more than 100 clinical sites in twelve countries around the world. The Mass General-led study was made up of an ethnically diverse group of nearly 800 male and female participants between the ages of 40 and 75. Although significant narrowing of the arteries was rare in the participants, nearly a quarter of them had plaque in their arteries, which the researchers considered to be an indication of vulnerability to future cardiovascular problems. The plaque burden found in these patients was also associated with higher levels of arterial inflammation and immune system activation independent of traditional risk scores. The scientists assessed two biomarkers to determine these higher levels

Expanding Medicare would reduce health care disparities

Lowering the eligibility age from 65 to 60 has been the subject of ongoing discussion in the U.S. Congress. An analysis by a team of health care policy researchers at HMS and the Yale School of Public Health has found that such a change would result in substantial reductions in racial and ethnic disparities in health insurance coverage, access to care, and self-reported health. The findings, say the researchers, also showed that a change would significantly improve access and care for people in all regions of the country. Wallace J et al., JAMA Internal Medicine, July 2021

of inflammation: LpPLA2, linked with arterial inflammation, and interleukin-6, associated with immune system activation. The scientists found increased levels of interleukin-6 in people with HIV who were relatively healthy. Increases in this biomarker, they say, could be predictive of the damaging effects that immune system activation has over time on people who are taking antiretrovirals therapeutically for HIV. Hoffmann U et al., JAMA Network Open, June 2021

PULMONARY MEDICINE

behaviors, contribute to this phenomenon. Evidence of the role the internal clock may have was recently uncovered in work by HMS investigators at Brigham and Women’s Hospital and colleagues at Oregon Health and Science University. Twenty million people in the United States have asthma and as many as 75 percent of them report experiencing greater severity at night. Many behavioral and environmental factors, including exercise, air temperature, posture, and sleep environment, are known to influence asthma severity. To untangle the influence of the circadian system from that of sleep and other behavioral and environmental factors, the researchers enrolled seventeen participants with asthma who were not taking steroid medication, but who used bronchodilator inhalers when needed, in two complementary laboratory protocols where lung function, asthma symptoms, and bronchodilator use were continuously assessed. Both protocols showed that participants with asthma had their lowest lung function during the circadian night, around 4 a.m., and a worsening of asthma that normally may be unnoticed during sleep. Using a mathematical model, the team found that there were additive influences from the circadian system and the behavioral sleep/wake cycle, suggesting that both circadian and sleep effects may contribute to worsening asthma severity. Taken together, the study’s findings indicate that people who experience severe asthma have not only the greatest circadianinduced drops in pulmonary function at night, but the greatest changes induced by behaviors, including sleep.This outcome could have important implications for studying and treating asthma. Sheer FAJL et al., PNAS, September 2021

Insight gained on why asthma worsens at night that asthma symptoms can worsen in the nighttime with some speculating that the body’s internal circadian clock, together with sleep and other PEOPLE HAVE LONG OBSERVED

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DISCOVERY AT HARVARD MEDICAL SCHOOL

Kitchen Aid

Kim H et al., Gastroenterology, August 2021

HANDMADE PICTURES/ISTOCK/GETTY IMAGES

CONSUMING HIGHER AMOUNTS of vitamin D from dietary sources such as fish, mushrooms, eggs, and milk may protect against youngonset colorectal cancer or precancerous colon polyps, say HMS researchers at Dana-Farber Cancer Institute and collaborators at other institutions. Their study found that a total vitamin D intake of at least 300 IU per day—about three 8-ounce glasses of milk—was associated with an approximately 50 percent lower risk of developing young-onset colorectal cancer. They also found that vitamin D consumed in the diet had a greater protective association than vitamin D taken in supplements. The findings could inform vitamin D intake recommendations for adults under age 50.

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HM INDEX: OF THE 50 TO 70 MILLION PEOPLE IN THE UNITED STATES WITH A SLEEP DISORDER, 25 MILLION HAVE OBSTRUCTIVE SLEEP APNEA.

SLEEP MEDICINE

Exercise may lower risk for a type of sleep apnea A STATISTICAL ANALYSIS of potential associa-

tions between physical activity, sedentary time, and diagnoses of obstructive sleep apnea has found that more active, less sedentary lifestyles lower the risk of the condition. The study, conducted by HMS researchers at Brigham and Women’s Hospital, drew upon data from approximately 130,000 women and men who participated in longitudinal studies known as the Nurses’ Health Study, Nurses’ Health Study II, and Health Professional Follow-up Study. Participants were followed for 10 to 18 years. The associations were strongest in women, adults over the age of 65, and adults who, according to body mass index measures, were identified as having overweight or obesity. Obstructive sleep apnea is a type of sleep apnea in which some muscles relax during sleep, resulting in an airflow blockage. People with severe forms of the condition are at increased risk for various heart problems, including abnormal heart rhythms and heart failure. The study is the first prospective work that simultaneously evaluates physical activity and sedentary behavior in relation to the risk for obstructive sleep apnea. The investigators encourage physicians to consider the findings and to highlight the benefits of physical activity to lower the incidence of obstructive sleep apnea in their patients. Liu Y et al., European Respiratory Journal, July 2021

PEDIATRICS

Intervention effort helps stem childhood obesity ALTHOUGH RATES OF CHILDHOOD OBESITY are at

historically high levels in the United States, there are few interventions that promote healthy weight gain in children from infancy

to age 2—a critical period for the development and prevention of childhood obesity. A novel intervention developed by HMS researchers at Massachusetts General Hospital, however, has yielded results that indicate it may be an important new tool in this effort. The intervention, known as the First 1,000 Days program, begins in the first trimester of pregnancy and focuses on lowincome families, which have the highest risk for childhood obesity. Its purpose is two-pronged: to provide individualized health coaching designed to encourage the adoption of healthy behaviors in women and their infants, and to promote systematic changes in the clinical care women and infants receive from public health programs and in community health centers. These changes include standardizing obesityprevention training for pediatric clinicians and staff, close tracking of infants’ weight gain, screening pregnant individuals for adverse health behaviors and social determinants of health, and providing educational materials and text messages to families to promote healthy feeding and sleeping behaviors for their infants. For their study of the effectiveness of this intervention, investigators compared weight outcomes in women and infants who received the intervention and in those who received usual care. They found that infants in the intervention group had 54 percent lower odds of overweight at six months and 40 percent lower odds of overweight at twelve months than infants who received usual infant care. The researchers will now focus on how best to disseminate the intervention to other health systems that care for lowincome families and on training frontline clinicians in how to incorporate the program into their practices. Taveras E et al., Pediatrics, August 2021

DIABETES

Proteins act against diabetic kidney disease ELEVATED LEVELS of three circulating proteins

have been found to help protect against kidney failure in diabetes, according to HMS researchers at Joslin Diabetes Center and their colleagues in industry and academia. The findings could provide biomarkers useful in detecting advancing kidney disease risk in people with diabetes and provide the basis for future therapies against the progression of end-stage renal disease, the most serious and advanced stage of diabetic kidney disease. The investigators used high-throughput proteomic platforms to profile levels of slightly more than 1,000 proteins in plasma samples from a biobank of samples from patients who had been treated at Joslin. All samples were from patients with diabetes and moderately impaired kidney function. Samples were separated into two cohorts: individuals with type 1 diabetes and individuals with type 2 diabetes. The patients, most of whom were white, had been followed for between 7 and 15 years. The aim was to identify which proteins were elevated in individuals with slow or minimal decline in kidney function over the follow-up period. The scientists found three proteins that were associated with protection against decline: fibroblast growth factor 20, angiopoietin-1, and tumor necrosis factor ligand superfamily member 12. Elevated levels of each protein were independently linked to a reduction of the odds of progressive kidney decline and progression toward end-stage renal disease.The combined effect of having elevated levels of all three proteins translated to very low risk for the severe disease. The researchers are developing protocols for measuring levels of the protective proteins in clinical settings, hoping that the analyses will be used to identify patients at risk of progression to end-stage renal disease. Md Dom ZI et al., Science Translational Medicine, June 2021

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ON ONCAMPUS CAMPUS NEWS NEWSFROM AT HARVARD HARVARD MEDICAL MEDICAL SCHOOL SCHOOL

noteworthy Advocate for faculty development heads faculty affairs On July 1, Grace C. Huang (fig. 1), a longtime leader in faculty development at Beth Israel Deaconess Medical Center, began her tenure as the School’s dean for faculty affairs and leader of the Office for Faculty Affairs. In their joint letter announcing the appointment in late April, George Q. Daley, MD ’91, dean of HMS, and Anne Becker, MD ’90, dean for clinical and academic affairs, said Huang was ideally suited for the position given her past experience in faculty development as well as her leadership and scholarship in the field. “She is widely recognized for her leadership in faculty development,” they wrote, and noted in particular her focus “on publishing in medical education and scholarly writing.” As dean for faculty affairs, Huang is responsible for the strategic leadership, oversight, planning, and implementation of the academic welfare of the Faculty of Medicine, including all aspects of the faculty promotions and appointments process. She also oversees academic activities, recruitment, development, academic advancement, and career satisfaction of the School’s diverse faculty and serves as a key advisor to faculty, department heads, and affiliated hospital leadership on these topics. Huang continues her appointments as an HMS associate professor of medicine and a hospitalist at Beth Israel Deaconess. At the hospital, she also serves as vice chair for career development and mentoring in the Department of Medicine, as director of its Office of Academic Careers and Faculty Development, and as co-director of the Beth Israel Deaconess Academy, a program dedicated to the educational development of physicians, scientists, clinicians, and other health care professionals throughout the Beth Israel Deaconess community. In addition, Huang directs the hospital’s

Online series crafted for doctors in pandemic hot spots In mid-July, the Postgraduate Medical Education unit of the HMS Office for External Education launched a new clinical education video series designed to provide evidence-based information about COVID19 treatment and prevention to frontline health care providers worldwide (fig. 2). The goal of the team leading the effort is to share evidence and practices for COVID-19 prevention and treatment with an emphasis on serving clinicians in hard-hit regions. Since its launch, the COVID-19 Clinical Education Series—available online as an open resource—has been viewed in eightythree countries. In his introduction to the series, HMS Dean George Q. Daley noted that although medical research has developed vaccines and identified therapeutic options, information on them has not reached all the places it’s needed. The video project, he said, was “inspired by the urgency” created by the pandemic and by “health inequities and dissemination of inaccurate information about disease detection, prevention, and treatment.” David Golan, HMS dean for research operations and global programs, who also delivered a video introduction to the series, emphasized Daley’s remarks, saying that “the goal of this video series is to disseminate timely, accurate, evidencebased information regarding COVID-19 to a worldwide audience of frontline health professionals and health care workers.” He noted that the videos were a collaborative effort involving experts from the HMS scientific and biomedical community. The sixteen videos cover a range of topics, each addressed by a renowned researcher in the given field. To facilitate

fig. 1

dissemination of information, the videos are divided into sections that answer guiding questions on the current topic. Topics covered include mechanical ventilation, oxygen management, vaccines, the prevention of hospital transmission, diagnostic testing, patient risk assessment and stratification, COVID-19 treatment, the complication of mucormycosis or “black fungus,” and pregnancy and COVID-19. A segment on pediatrics and COVID-19 information sources is planned, and translations into Arabic, French, Hindi, Portuguese, Spanish, and Swahili are underway. The series can be found online at hms.harvard.edu/covid-video-series

Faculty gender equity effort gets a new leader fig. 2

fig. 3

Marcia Haigis (fig. 3), a professor of cell biology in the Blavatnik Institute at HMS, has been named the School’s director of gender equity for faculty in science. In this position, which reports directly to Anne Becker, dean for clinical and academic affairs, Haigis will foster collaboration between HMS faculty and the office of Dean George Q. Daley to identify areas important to attaining gender equity among HMS faculty. Haigis will help prioritize and implement activities that will contribute to such parity, including those in support of mentoring, leadership, and career training. Although she will primarily focus on Quad-based faculty, her work will, when possible and appropriate, extend to activities at affiliate institutions. In this role, Haigis will continue and expand upon the gender equity work begun by Galit Lahav before her appointment in 2018 as chair of the Department of Systems Biology in the Blavatnik Institute at HMS.

RANDY GLASS

Rabkin Fellowship in Medical Education, a program for HMS faculty designed to help develop the skills needed to launch or advance academic careers in medical education or academic leadership.

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SPECIAL REPORT

I AGING

An Age-Old Desire THE CENTER FOR THE HISTORY OF MEDICINE, FRANCIS A. COUNTWAY LIBRARY OF MEDICINE

SINCE ANCIENT TIMES, people have searched for the secret to eternal youth, an

elixir that would pay the toll exacted by time. Scholars have traced this desire over millennia—from Gilgamesh’s search for immortality to Alexander the Great’s quest for a river rumored to cure the ravages of aging to Juan Ponce de Leon’s journey to find the mythic fountain of youth . A sixteenth-century Venetian nobleman, however, did Above, the opening page of the first volume of not need to travel to find the keys to health and longevity. Alvise (Luigi) Cornaro’s multivolume work, Dis- After decades of hedonistic living, Alvise (Luigi) Cornaro corsi della vita sobria or decided to flip his personal script. He began a caloriethe Temperate Life. restricted diet, part of what he called his temperate lifestyle. Years later, at age 74, he sat down to write Discorsi della vita sobria, an exegesis of his regimen for healthy aging. At age 77 he wrote a second volume; at 79, a third; and at 81, a fourth. He may have been planning a fifth when, at age 82, he died. Today, researchers are actively investigating myriad aspects of the aging process. In this issue, we talk to some of those scientists to find out what they are learning about this phenomenon of life.

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SPECIAL REPORT

I AGING I NEUROINFLAMMATION

Neuroinflammation, which normally guards against brain injury and infection, is increasingly being implicated in cognitive decline by Charles Schmidt

When Protection Goes Awry

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DUNG HOANG

During his internship at Beth Israel Hospital in the mid-1970s, Eric Larson, MD ’73, recalls that it wasn’t unusual to say that older people with cognitive decline had senile dementia or hardening of the arteries. n These catch-all phrases are rarely used today, however, as evidence increasingly connects age-related cognitive symptoms to neurodegenerative changes in the brain. Larson has watched, and been part of, this evolution in thinking. Currently a senior investigator at Kaiser Permanente’s Washington Health Research Institute in Seattle, Larson founded Adult Changes in Thought, a prospective cohort study that tracks brain aging and dementia in approximately 5,700 participants from the local population. n A striking observation from the study, he says, is that some people remain cognitively healthy despite what appear to be debilitating neuropathologic changes seen at autopsy. One recent study participant in particular, a woman who enrolled in the study decades ago, was “still very on top of things and very with it” right up to her death in her mid-90s, Larson says. Yet, the autopsy of her brain showed a pathology that normally would have been diagnosed as Alzheimer’s disease. “How was she seemingly resilient given her brain’s degeneration?” Larson asks. HARVARD MEDICINE | AU T U M N 202 1

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AGING

I NEUROINFLAM MATION

indings like this, say scientists such as Rudolph Tanzi, PhD ’90, the Joseph P. and Rose F. Kennedy Professor of Child Neurology and Mental Retardation at HMS and Massachusetts General Hospital, underscore the powerful role of neuroinflammation in conditions such as Alzheimer’s disease, Parkinson’s disease, Lewy body dementia, and frontotemporal dementia. Rates for these neurodegenerative illnesses are increasing steadily with the aging of the U.S. population, and it is thought that worsening symptoms can be blamed on the havoc inflammation wreaks on brain regions involved in thinking, memory, and movement, or, in the case of frontotemporal dementia, personality, behavior, and language. Harmony lost

“By wiping out affected parts of the brain, immune cells are aiming to keep the infection from spreading. These cells didn’t get the memo about how long we’re living now.”

JOHN SOARES

Coordinated in part by the brain’s resident immune cells—microglia and astrocytes— neuroinflammation ordinarily protects against infection and injury. But when spinning out of control, it “can kill ten times more neurons than the pathological changes that set it off,” says Tanzi, who also co-directs the

Rudolph Tanzi

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McCance Center for Brain Health at Mass General. Scientists have linked neuroinflammation with cognitive decline and higher risks for age-related cognitive impairment. And autopsies show clear evidence of it in the brains of people who have died from Parkinson’s disease. Conversely, signs of neuroinflammation in the brains of people who do not exhibit Alzheimer’s symptoms “are for the most part nonexistent,” says Tanzi, despite their having other disease-related pathologies. Beth Stevens, an HMS associate professor of neurology, a research associate in the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, and a member of the Broad Institute of MIT and Harvard, says that neuroimmune signaling and its role in age-related neurodegeneration is galvanizing the field. “It’s a really exciting time to be studying this,” she says. “Immune pathways are clearly part of the story. And we need to figure out how and why.” Much of the evidence so far has come from studies of Alzheimer’s disease, which, say Tanzi and others, dwarfs the other neurodegenerative conditions in terms of funding and research. The onset of Alzheimer’s is triggered by two proteins: amyloid beta, or A-beta, and tau. The precursor of A-beta ordinarily participates in neural growth and repair, while tau normally helps to stabilize the structure, or “scaffolding,” of neurons. Both proteins can become troublesome with age, however. Instead of dissolving away in solution, A-beta can start clumping together to form insoluble amyloid plaques between nerve cells. Similarly, tau can aggregate into structures called neurofibrillary tangles that also block nerve cells from communicating. In Parkinson’s disease, Lewy bodies, which are tiny round structures made of the protein alpha-synuclein, accumulate in neurons. And like plaques and tangles, the Lewy bodies are neurotoxic and therefore capable of triggering neuronal cell death, leading to an immune reaction. Domino effects

Immune cells in the brain usually play housekeeping roles: Microglia consume debris, such as amyloid, and dead or infected cells and prune excess neuron-to-neuron junctions, known as synapses, allowing brain

circuits to run smoothly. Astrocytes help build up the blood-brain barrier, which protects against infection, while also supplying neurons with nutrients. But like Dr. Jekyll and Mr. Hyde, microglia and astrocytes can take on more sinister personalities, during which they “throw off the apron, put on SWAT gear and become killers,” Tanzi says. Francisco Quintana, an HMS professor of neurology at Brigham and Women’s Hospital, has spent years investigating what drives immune cells to flip like this. Quintana grew up in Argentina, and says he was inspired to get into neurology after watching his grandfather—who he describes as a towering figure and a personal hero—succumb to a neurodegenerative disease. Quintana made an important discovery that describes how the inflammatory cascade can begin and perpetuate in the brain: pathological subsets of microglia and astrocytes communicate with each other to coordinate neuronal attacks. In some cases, these attacks can be instigated by T cells, a type of white blood cell important in the immune response, entering from outside the brain. Quintana found that when T cells secrete a specific protein, that protein acts to shift transcriptional profiles in astrocytes, causing them to turn on genes that trigger inflammation. When activated in this way, astrocytes spew out free radicals, such as nitric oxide, which in turn activate microglia, making them become neurotoxic as well. By engaging in this cross talk, astrocytes and microglia launch a chronic assault on brain tissue that persists even without further T cell involvement. The inflammatory reaction, Quintana says, “takes on a life of its own.” Tanzi’s research shows that neuroinflammatory cascades can also occur in the opposite direction, with microglia activating astrocytes, which in turn attract T cells. In 2008, Tanzi identified one particular gene, called CD33, that serves as an on switch for Alzheimer’s disease-associated neuroinflammation. Located on microglial cell surfaces, “this is the ‘bad-guy’ gene that tells the cell to produce a bunch of cytokines to get astrocytes involved in the killing,” he says. Cytokines are proteins that mediate the body’s immune reaction, usually by modulating it, but, at other times, by increasing it.

Immune cells in the brain usually play housekeeping roles. But like Dr. Jekyll and Mr. Hyde, they can take on more sinister personalities.

In later research, Tanzi showed that CD33’s activity coordinated with TREM2, a complementary “good-guy” gene in microglia. If the expression of TREM2 increases, the microglial cells remain as housekeepers. But if TREM2 is mutated, or otherwise defective, CD33 can switch the microglial cell to an inflammatory mode. Mutations in TREM2 have been linked to Alzheimer’s disease and to Parkinson’s disease. Inside and out

Why would the brain’s immune cells become so destructive in the first place? One explanation is that they haven’t yet adapted to increasing human life spans. The cells were programmed during evolution to eliminate infections. So, when they see a dying neuron, Tanzi says, they simply assume it’s infected, and then shift from housekeeping to inflammation. “By wiping out affected parts of the brain, they’re aiming to keep the infection from spreading,” Tanzi says. “These cells didn’t get the memo about how long we’re living now and that neurons die for reasons other than infection.” Importantly, different triggers can set these neuroinflammatory cascades in motion; not just infection, plaques, tangles, and Lewy bodies, but also pollutants and physical trauma. Tanzi wears many hats, one of them being a brain health advisor to the New England Patriots football team. Among the responsibilities that come with that role, he says, is “trying to help these guys avoid later problems with chronic traumatic encephalopathy,” a neurodegenerative condition caused by repeated blows to the head. Like frontotemporal dementia, chronic traumatic encephalopathy is a “tauopathy;” it’s characterized by neurofibrillary tangles that form in the absence of amyloid plaques. Pivot

Research connecting inflammation with neurodegeneration is still in its early days, and Bruce Yankner, an HMS professor of genetics and neurology and co-director of the Paul F. Glenn Center for the Biology of Aging , cautions that questions remain about the degree to which inflammatory processes can be lumped together in different condiHARVARD MEDICINE | AU T U M N 202 1

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Beth Stevens

JOHN SOARES

tions. “These diseases likely share common features, such as activation and proinflammatory responses of microglia and other cell types,” Yankner says. “But the way in which these responses overlap between diseases is very poorly understood.” Also not well understood is how the brain protects itself from inflammation and agerelated changes. Still, researchers are making headway. Yankner and his team published a study in 2014 that revealed one intriguing mechanism. They found it while investigating changes in age-related gene expression in the prefrontal cortex, the part of the brain responsible for executive functions such as planning and social behavior. Their research showed that a protein called REST affords some resilience against cognitive declines. Yankner, who also is a professor of neurology at Boston Children’s Hospital, is wellknown for his 1990 discovery that A-beta is toxic to neurons, a finding that led to what’s widely known today as the amyloid hypothesis in Alzheimer’s disease. According to that hypothesis, accumulating A-beta in the brain is the fundamental cause of Alzheimer’s and the driving force behind its initiation. With this newer finding, Yankner’s research team reported that REST is lost in patients with Alzheimer’s, but present in the brains of people who retain high cognitive performance until death, even if they have evidence of disease pathology at autopsy. Findings like these galvanized researchers in the field, who are now “pivoting away from pathological hallmarks of disease toward neuroimmune pathways that are clearly part of the story,” Stevens says. In July, Tanzi and his colleagues published findings in Nature showing that a small subset of astrocytes can actually push back on the brain’s inflammatory responses and try to quell them. Making up about 4 percent of the total astrocyte pool, the cells in this specialized subset produce a molecule called interleukin-3 that binds to microglial cells and turns them back into housekeepers capable of removing debris such as amyloid. A crucial player in that helpful interaction turned out to be TREM2. According to Tanzi, microglial cells will go back to housekeeping if they detect interHARVARD MEDICINE | AU T U M N 202 1

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leukin-3 but that doing so requires them to express the molecule’s receptor. “What we found is that TREM2 tells microglial cells to turn up the interleukin-3 receptor, so they can go back to being beneficial,” Tanzi says. Interleukin-3, he added, “has the potential to be a new treatment if we can figure out how to use it.” In Stevens’ view, therapeutic opportunities like these will depend on a better understanding of how the brain’s immune cells shift transcriptional states to carry out particular functions. The cells have many different roles, she says, and will adopt varied states accordingly. “At the moment, we don’t know enough about whether it’s one population of cells that is detrimental, and if we should target those cells, or whether we should target their state, and shift them back to a more beneficial state,” Stevens says. “If so, we could target the bad and promote the good. And to get there, we need to isolate the specific states or populations of cells and understand their functions. That’s what the field is working on now.” Ways and means

JOHN SOARES (FACING PAGE)

New technologies are aiding in that endeavor. For instance, scientists in the field are turning to single-cell RNA sequencing to track disease-associated transcriptional states in microglia and other immune cell types. Quintana used these tools to identify which subsets of microglia and astrocytes promote neuropathology, and he also relied on a technology called RABID-seq to study how the cells communicate with each other.

Further opportunities come from culturing organoids, which are three-dimensional bits of brain tissue, in a dish. By using culture media containing the proper chemical factors, adult human cells—including those taken from patients—can be brought back to a near-embryonic state, then prodded to grow into any sort of cell from the body. Tanzi adopted this approach to create tissue models of Alzheimer’s disease, which he uses in a number of studies, including ones investigating how T cells in nerve tissue throughout the body infiltrate the brain and worsen inflammation. His insights add to a growing body of evidence that neuroimmune signaling can reach well beyond the brain, even to the gut microbiome. While the vast assortment of bacteria, viruses, and other microbes inhabiting the digestive tract have many beneficial roles, “it can also amplify inflammation in the brain and make it worse,” says Howard Weiner, the Robert L. Kroc Professor of Neurology at HMS and Brigham and Women’s. In his book The Brain Under Siege, Weiner presents supporting evidence obtained from mice bred to mimic features of Alzheimer’s disease. Treating the animals with antibiotics altered their microglia, converting the destructive cell type to the protective type. Similarly, evidence suggests that Parkinson’s disease is related somehow to microbial changes in the gut, likely through inflammatory pathways. Weiner cites research using mouse models of Parkinson’s disease. When bred in germ-free conditions, the animals—which have virtually

no gut bacteria—have fewer Lewy bodies in By using culture media the brain and never develop problems with one of the symptoms of Lewy containing the movement, body dementia. Weiner speculates this could proper chemi- be because microbially-induced inflammation cal factors, somehow boosts the gut’s production of alphaadult human synuclein protein, which is then transferred to the brain via the vagus nerve. Adding to cells can be brought back evidence connecting Parkinson’s disease to the gut-brain axis, Weiner writes, is that people to a nearwith inflammatory bowel disease are also at embryonic higher risk of Parkinson’s. state, then Stevens asserts that further progress toward understanding the connection between prodded to grow into any inflammation and age-related neurodegeneration will come from using molecular sort of biomarkers measured in the body’s fluids. She tissue from and her collaborators are analyzing blood and the body. cerebrospinal fluid from people with neuro-

“Incorporating new neuroimmune biomarkers into ongoing clinical trials could be an exciting new direction and advance for the field.”

degenerative conditions and from those without such conditions, and are performing deep, large-scale comparative analyses of their proteins. Soluble forms of TREM2 can be detected in cerebrospinal fluid, “and there’s evidence that it changes in people with Alzheimer’s disease,” she says. “That’s an excellent example of a biomarker that’s being read out in cerebrospinal fluid now, and there are going to be many others as well. Incorporating new neuroimmune biomarkers into ongoing clinical trials could be an exciting new direction and advance for the field.” Meanwhile, in Seattle, Larson and his colleagues are looking forward to the next phase of the Adult Changes in Thought study, which recently won a five-year federal grant totaling $55.6 million—triple its prior funding. Participants agree to baseline tests and to evaluations every two years. Many consent to donate their brains to research when they die. Larson points out that the study, which began in the late 1980s, is among the few studies that collect control brains from people who don’t develop dementia during study observation. “The funding environment has dramatically improved and so has the technology,” he says. “We’ve learned a lot already, and this new support means that in the next five to ten years, we’re going to learn a lot more.” Charles Schmidt is a writer based in Maine. HARVARD MEDICINE | AU T U M N 202 1

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ON CAMPUS NEWS AT HARVARD MEDICAL SCHOOL SPECIAL REPORT AGING CLIMATE AND THE CLINIC

When heat intensifies, older adults weaken— but they don’t have to

Melting Point

BY STEPHANIE DUTCHEN

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HE NEWS IN SUMMER 2021 was almost as oppressive as the heat itself. Boston sweated through its hottest June on record. Lytton, British Columbia, reached an unheard-of 121 degrees Fahrenheit as the Pacific Northwest baked under a heat dome. Another dome in August stifled the Mediterranean. As records toppled, lives were lost. Early investigations suggest that nearly one thousand people died as a direct result of the Pacific Northwest heat wave. Most of them were older adults. In Oregon’s Multnomah County, which includes Portland, the average age among those who perished was 70. People over 65 accounted for three-quarters of Washington’s deaths. These proportions, which echo the casualties following extreme heat events around the world in recent years, re‑ iterate that older people are among those most vulnerable to falling ill and dying when the mercury rises. More than 80 percent of the estimated 12,000 people in the United States who die of heat-related causes annually are over age 60, according to the journalism resource Climate Central. As Earth gets hotter and human populations skew older, heatrelated fatalities among older adults are expected to grow. Climate change drives more frequent, more intense, and longer heat waves. It raises nighttime lows, preventing body temperatures from resetting when the sun sinks. Even short of heat waves, the volatility that climate change provokes in day-to-day highs can truncate the lives of older people with certain health conditions, researchers at the Harvard T.H. Chan School of Public Health wrote in a 2012 study in PNAS. Clinicians can help. A survey published in the Annals of Global Health in 2015 indicated that primary care physicians are U.S. adults’ most trusted sources of information related to climate change and health. The medical toolkit grows as research continues to reveal the biological and social factors that make older adults more susceptible to heat and identifies the most effective interventions. Studies show that it can be hard for even healthy older adults to tell when it’s too hot or if they’re dehydrated. Cognitive decline exacerbates these problems. Older bodies also hold more heat than younger ones when the temperature climbs. Glands don’t release as much sweat. The heart doesn’t circulate blood as well, so less heat is released from vessels in the skin. Systems from the cardiovascular to the immune struggle to compensate. Older adults are likely to have chronic health conditions and to take medications that contribute to heat intolerance. Clinicians best serve patients when they stay abreast of the literature on risk factors and, when heat looms in the forecast, consider warning, checking in with, or adjust-

ing relevant medications of the vulnerable, says Francesca Dominici, the Clarence James Gamble Professor of Biostatistics, Population, and Data Science at the Harvard Chan School. “So many heat-related hospitalizations and deaths are preventable,” she says. While doctors have known about many risk factors for decades, others are emerging. By applying statistical expertise to vast health care and meteorological data sets, Dominici and colleagues have uncovered previously unappreciated conditions that raise older people’s likelihood of being hospitalized during and immediately after heat waves. These findings, first reported in JAMA in 2014, include fluid and electrolyte disorders and urinary tract infections. Data science is “giving us enormous ability to disentangle the major causes of a hospitalization and say reliably that it was the heat that made someone sick,” Dominici says. What constitutes excessive heat goes beyond the National Weather Service definition of a heat wave, according to findings from researchers including John Spengler, the Akira Yamaguchi Professor of Environmental Health and Human Habitation at the Harvard Chan School. “We’re seeing problems with hydration, sleep, and cognitive decline at 85 degrees and lower,” he says. “It makes us rethink what real heat stress is about.” Dominici and others point out that temperatures don’t have to hit 90 or 100 degrees to be dangerous; they only have to rise beyond a region’s normal range. Acclimation matters. Heat tends to cause more deaths at the start of summer than at the end. More deaths occur when heat strikes areas unaccustomed to it. Finally, age intersects with socioeconomic factors to compound heat vulnerability. Older adults who are poor, who identify as Black or Hispanic, or who live in cities are more likely to become sick or die from excessive heat. Poorer neighborhoods tend to have fewer shade trees and reach a boil faster than wealthier environs. Having air conditioning at home isn’t enough if a patient can’t afford to run it. The Arizona county that includes Phoenix reported that of those who died indoors of heat-related causes in 2019 fully 91 percent had air conditioners, but the units were turned off, turned too low, or broken. Older adults with mobility issues or who lack social networks are less able to access resources such as cooling centers or have people check on them. Science and medicine have made tremendous progress in understanding how our warming climate threatens human bodies, says Dominici. Now it depends on everyone, including clinicians, to act quickly enough to avoid the worst. Stephanie Dutchen is manager of feature content and multimedia in the HMS Office of Communications and External Relations. HARVARD MEDICINE | AU T U M N 202 1

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SPECIAL REPORT

I AGING I DIGNITY AND CARE

Many worry that respect and empathy for older adults are being lost in our system of health care, a situation, they say, that will harm people and damage our culture by Elizabeth Gehrman

A Place for

HARVARD MEDICINE | AU T U M N 202 1

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Dignity? MATTIAS PALUDI

IN 1965

the British band The Who released “My Generation,” which would become an anthem of its time. As the iconic guitar-smashing songwriter Pete Townshend recalls in his autobiography, Who I Am, he penned the song—with its famous line, “I hope I die before I get old”—on his twentieth birthday, in response to his car being towed at the behest of the Queen Mother. But nearly a half-century later the mellowing rock star had changed his tune. “I want to age with some dignity,” Townshend said in a 2009 interview with the newspaper The Australian. “I just want to be part of the human race.” HARVARD MEDICINE | AU T U M N 202 1

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doesn’t seem a lot to ask. But as the oldest of Townshend’s baby boom fans turn 75 this year and the youngest approach 60, aging with dignity, for many, is looking less attainable than ever. “We’ve created a world where many millions of people get the opportunity to grow old,” says William Thomas, MD ’86, a geriatrician, author, and public speaker based in Ithaca, New York. “But at the same time we’re draining the dignity and worth from the experience of aging. As a society we have failed to understand that people living with frailty and dementia can have a damn fine life. We think they are a class of zombie and we’ve set up zombie facilities to store them.” Isolating people in this way, he says, reinforces the illusion that “old people can’t give, they can only receive. That’s extremely damaging, not only on a personal level but also on a cultural one.” Breaking point

JOHN SOARES

Muriel Gillick

While only 2 percent of people 75 to 84 years old in the United States and 8 percent of those 85 and older live in the nation’s nearly 16,000 nursing homes, a fifth of the population dies in them, largely

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JOHN SOARES

during rehab stays after being discharged from hospitals. Two-thirds of 65-yearolds will need long-term care services at some point in their lives, for an average of 28 months, and more than 30 percent of older adults need help with activities of daily living, which include walking, feeding, dressing, grooming, bathing, and toileting, according to the U.S. Centers for Disease Control and Prevention. Nearly a third of people older than 85 also have Alzheimer’s, which vastly increases the need for long-term care. Traditional sources of social capital are not as relevant as they have been in the past, in part because families are smaller and people may live farther from loved ones. Problems with nursing homes, commonplace before the pandemic, were brought into stark relief early in crisis, when nearly a third of all COVID-related deaths were reported to have occurred in individuals living in these facilities. “The system was designed to fail,” says David Grabowski, an HMS professor of health care policy, given that it relies on two beds to a room, shared lavatories, staff shuttling between home and work every day, and underpaid certified nursing assistants and orderlies working in multiple facilities. But even before the pandemic, hardly a month went by without headlines blaring a nursing home scandal somewhere in the country. While accurate numbers are hard to come by, partly the result of underreporting, in 2013 the National Center for Victims of Crime indicated that more than 25 percent of nursing home residents experienced physical abuse, nearly 20 percent endured psychological abuse, and slightly more than 15 percent suffered gross neglect. The picture isn’t always rosy when older adults live at home, either. Not only are they vulnerable to abuse and neglect in these living situations, but study after study has shown that caregiving can cost spouses, friends, adult children, and other relatives their own health, compromise their work productivity and career opportunities, and cause them significant financial and emotional distress.

David Grabowski

“We often view aging as a family issue and not a policy issue,” Grabowski says. “But we all pay collectively when family caregivers suffer from physical and mental health troubles and have to leave the workforce. We haven’t internalized this problem as a country and created a true system for caring for older adults. We’re in a crisis of low-quality care and underinvestment, and our current approaches are not sustainable.” Attention required

And it’s going to get worse. By 2050, the number of adults over 65 in the United States is expected to double from the current 46 million, mirroring worldwide trends. The U.S. Census Bureau maintains that this growth may spur “greater demands for health care, in-home caregiving, and assisted living facilities,” even as the number of both professional and family caregivers is projected to decline, according to think tanks such as the AARP Public Policy Institute. At the same time there will be fewer workers contributing to Social Security, which provides the bulk of most people’s incomes after age 65, and to the payroll taxes that fund Medicare and Medicaid, which supply health insurance and long-term care, respectively, for older adults.

By 2050, the number of adults over 65 in the United States is expected to double from the current 46 million.

“We are definitely not prepared,” Gra bowski says. “There are a lot of options today to change the system, and I was hopeful about big policy changes in the wake of the pandemic.” But, he continues, “I can already feel public attention turning to other issues. I don’t know if our society has the energy or enthusiasm to take this on. If the pandemic didn’t do it, what will it take?” While the issue of childcare has been on the political agenda for decades, as a country we’re “just starting to have a conversation about elder care,” notes Judy Kwok, an HMS instructor in medicine and a geriatrician with Cambridge Health Alliance. “Part of it is just ageism. Unlike some other countries, we don’t value older adults the way we do children, and we don’t put enough resources into their care.” Sexism and racism also play a part, experts agree. More than three-quarters of family or other informal caregivers are women, according to the Institute on Aging, and the majority are unpaid. “I’m sure if more men had to step up it would become an issue we’d pay attention to,” Kwok says. In nursing homes—about 70 percent of which are for-profit—almost a third of direct care, housekeeping, and maintenance staff are immigrants. The relatively low wages and benefits they receive combine with high levels of burnout to create a mean staff turnover rate of 128 percent, with the rate of staffing changes at some facilities exceeding 300 percent, according to a 2021 study published by Grabowski and two colleagues at the University of California, Los Angeles. This, in turn, negatively affects the quality of care residents receive. Another reason the problem has been back-burnered for so long is that “America is known for its relentless focus on the individual,” says Muriel Gillick, MD ’78, a physician who specializes in geriatrics and palliative care and an HMS professor of population medicine, part-time, in Harvard Pilgrim Health Care Institute’s Department of Population Medicine. Gillick’s 2017 book, Old and Sick in America, examines how forces including government regulators, insurers, drug companies, doctors, lawyers, and even, often inadvertently, families “interact to create the system we have.” But at bottom, she says, “American culture is focused on HARVARD MEDICINE | AU T U M N 202 1

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people doing for themselves. If you can’t, well, just tough.” It doesn’t help that we sometimes focus on the wrong things. “This new Alzheimer’s drug that came out recently was so expensive,” says Kwok, referring to aducanumab, which was developed by Biogen at a cost of $2.5 billion and called “marginally effective at best” by the science news website STAT. “That’s money that could have been put toward hiring and paying our current home health aides and paid caregivers better so that they could be less stressed out, not have to work three jobs, not have to travel an hour to get to their patients because they can’t afford to live in a city. As a society we want these big magical fixes, but we don’t put enough resources into the care that really does matter day to day.” Finally, we need “greater transparency and accountability about how providers are spending money,” Grabowski says, along with a restructuring of payment systems. While about 35 percent of nursing home residents pay out of pocket or through private longterm care insurance, most stays are covered by Medicaid, which subsidizes long-term care but requires seniors to spend down any assets they may have in advance. Medicare, which kicks in at 65 and provides health insurance regardless of income, covers neither custodial care such as bathing, dressing, and eating, nor long-term care beyond one hundred days. Because Medicare is funded federally and Medicaid by both state and federal governments, “each program tries to push costs to the other and no one’s worried about the overall quality of care,” Grabowski says. Plus, Gillick points out, cutting Medicaid is one of the best ways for states to find revenue when their budgets fall short. “And who gets shafted when you do that?” she asks. “Frail older people who can’t protest, and home health aides and others who may not be able to advocate for themselves. So yeah, it’s a mess.” Outside the box thinking

Judy Kwok

JOHN SOARES

Still, there is some good news. A few innovators are making inroads in changing the culture of elder care. The joint Medicare/ Medicaid model PACE, or Program of AllInclusive Care for the Elderly, for example, HARVARD MEDICINE | AU T U M N 202 1

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was started in San Francisco in the 1970s in response to residents in Chinatown and elsewhere in the city who needed more care but didn’t want to go outside their communities to receive it. The 272 PACE centers nationwide today, including the one Kwok works for through Cambridge Health Alliance, provide “a care plan very tailored to the frail, complicated older adults we see,” she says. At least twice a year, everyone on the client’s interdisciplinary team—the MD or nurse practitioner, the social worker, the occupational therapist, the dietitian, the case manager, and the activities coordinator— meet with the client and family and discuss care going forward. “We are required to provide patient-centered care, whatever that means for each person,” says Kwok. “Everyone’s functional status, education, and family structure is different, and of course we also account for racial and ethnic diversity. A quote I’ve heard that sort of sums up our philosophy is, ‘If you’ve met one 90-year-old, you’ve only met one 90-year-old.’ ” Research has shown that such homebased care not only saves insurers money, but reduces hospitalizations and the need for long-term institutional care, and more important, results in verifiably longer, happier lives for participants. PACE and similar programs are in the vanguard of a concept that is increasingly driving the design of care for older adults: rebalancing. “Most long-term care today is incredibly expensive and yet patients are not getting very good quality at all,” says Grabowski. “It’s a real disconnect.” Rebalancing aims to level the scale a bit by shifting care toward home-based services and putting more control in the hands of clients and their families while also saving Medicaid money on room and board. “Rebalancing looks at the state budget for supporting a life of dignity for older people,” says geriatrician Thomas. “It used to be that about 97 percent of it went to nursing homes. But over the past ten years that fraction is going down and the amount going to supporting older people is going up.” Thomas, a self-described “nursing home abolitionist,” is the architect of two initiatives that have been changing lives for decades.

The first, developed in the 1990s with his wife, Judith Meyers-Thomas, is the Eden Alternative, a philosophy that now guides thousands of residential communities for older adults and is based on offering residents purpose through variety, inclusion, empowerment, and independence. Among other innovations, the Thomases and those who adopted their tenets brought plants, pets—including dogs, cats, rabbits, and parakeets—and children into nursing homes for residents to care for and interact with. Now, with hundreds of sites in the United States and around the world using their model, research has shown that quality of care has improved, levels of resident engagement have increased, and staff turnover and sick days have been reduced. A decade later Thomas partnered with Steve McAlilly, a senior services executive in Mississippi, to found the Green House Project, which employs Eden Alternative values in homey, purpose-built residences. These houses have ten to twelve private bedrooms and bathrooms, higher staff-to-patient ratios, and less administrative interference. Support from the Robert Wood Johnson Foundation has allowed the concept to grow to more than three hundred locations that are either open or under development in thirty-two states, and the evidence so far is that the staff is significantly more engaged with residents, avoidable hospitalizations and readmission rates are lower, and family satisfaction is higher. Perhaps most surprising to those who focus on costs, both interventions saw operating margins and market position tick up. Thomas concedes that currently most of the less orthodox models are run by nonprofits, but says, “You’re competing against a nineteenth-century relic. There should be some entrepreneurs out there who can beat that.” Of course, none of the nontraditional settings coming onto the scene can ultimately succeed without changes from doctors, older adults, and families. Doctors, says Gillick, need to take the perspective of their patients more seriously, even when it seems to fly in the face of medical doctrine. “I had a patient once with very mild dementia and a fairly treatable cancer,” Gillick notes. “She had seen her sister progress through dementia, and she

The paradigm is to stay in housing that was conceived and built not for aging but for raising children. That can be very isolating for older adults.

regarded her cancer as an opportunity to exit more gracefully from the world. Her oncologists found this tremendously perplexing, because they had a treatment that was not terrible and had a reasonable prospect for longer life. But doctors need to think about the effect of treatment on the trajectory of patients’ lives.” Older people and their loved ones, too, need to look ahead, she maintains, but can’t do that without better communication from their health care providers. “A lot of the problems that develop in medical care result from unfortunate decisions being made,” she says. “We need to give caregivers more responsibility, and provide them with the support and education they need to make those decisions.” She thinks such a bottom-up approach would result in fewer hospitalizations, but would also require “some energizing from above” in the form of legislative changes. “This doesn’t require some great technological fix to solve,” she says. “We kind of know how to do this geriatric care stuff, or at least how to do it a lot better than we are. It seems a shame that we don’t make the effort.” Thomas agrees, pointing out that for aging individuals, thinking ahead extends beyond medical care to another big decision that should be made early on: where you’re going to live. “We need better communities, so people can look out for each other,” he says. He says today, the paradigm is to stay in housing that was conceived and built not for aging but for raising children. That can be very isolating, cutting older adults off from the rest of the world, when instead they could be seeking new communities and new friends with “intentionality and effort.” Thomas is now working on a framework that clusters compact single-story homes for older adults in multigenerational communities. While this type of MAGIC— multi-ability/multi-generational, inclusive community—may be an outlier today, he considers broader adoption of the model all but inevitable. “Aging is a team sport,” he says. “If you’re playing alone, you’re going to lose.” Elizabeth Gehrman is a Boston-based writer. HARVARD MEDICINE | AU T U M N 202 1

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SPECIAL REPORT

I AGING I PROLONGED GRIEF

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OME PEOPLE ARE FORTUNATE ENOUGH to find a life partner they consider their soul mate. Such was the case for Jodi, a patient of M. Katherine Shear, the Marion E. Kenworthy Professor of Psychiatry at the Columbia University School of Social Work. Shear says Jodi and her second husband were close, practically attached at the hip, and they enjoyed each other’s company immensely. When he became chronically and then terminally ill, Jodi stayed by his side, taking him to the hospital on several frightening occasions when it looked like he might have reached the end. Jodi’s husband repeatedly beat the odds, and with each milestone, he and Jodi would gain more hope that he would be the exception, the one who would not lose out to a deadly condition. Then, on a rare day when Jodi had stepped away from home, her husband’s heart stopped. Riddled by guilt and loss, Jodi turned inward, avoiding family, friends, and places she and her husband had frequented. She was captive to her memories, and she sidelined herself from life for nearly four years. Experiencing grief is natural and necessary, and the vast majority of people suffering the loss of a loved one experience it for a predictable period of time—generally six to twelve months. But sometimes, people like Jodi become stuck. Their grief remains acute, and they can’t move forward. They experience what is known as prolonged grief.

Ensnared in despair

A Sadness So Profound

K. MITCH HODGE

Prolonged grief often goes undiagnosed even though treatment can be pivotal to overall well-being by Amanda Loudin

When a loved one dies, those left behind naturally feel various levels of sadness, anger, guilt, fear, and loneliness. These are the hallmarks of acute grief. “It’s a normative response to experience an initial period of loss that is both intense and time-limited,” says Naomi Simon, MD ’92, a professor of psychiatry at the NYU Grossman School of Medicine. “It will change form as time goes on, and it will vary from person to person and culture to culture.” Eventually, acute grief will slip to the background, integrating the emotions associated with the loss into survivors’ lives. “This is the notion that you have processed the permanence of and adaptations to loss,” says Simon. “The mind, heart, and life have adapted. Grief hasn’t ended, but it has changed.” For about 7 percent of those who are bereaved, however, grief sticks around in a deeply painful manner, preventing them from moving forward and healing. Prolonged grief—also referred to as complicated grief—traps these individuals in a loop of despair from which they can’t escape. Determining when grief becomes pathologic depends on whose guidelines are being followed. In 2015, the WHO issued a new guide on the management of mental health conditions in humanitarian emergencies, saying that grief lasting beyond six months should be considered prolonged grief disorder and specialists should be consulted when determining treatment. In 2018, the American Psychiatric Association, in the fifth HARVARD MEDICINE | AU T U M N 202 1

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AGING

I PROLONGED GRIEF

edition update of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), added the disorder, describing it as grief that persists for one year or more. Mired and bereft

Naomi Simon

rience prolonged grief. Relationship to the deceased, in particular if it was a child or a spouse, was more predictive of the condition. After this pandemic, rates of prolonged grief among older adults may move even higher, says Simon, but given the DSM-5’s requirement that grief persist for twelve months following a loss, not enough time has elapsed for data to be assessed. Yet, caregivers like Simon are preparing. A June 2020 letter in Psychiatry Research issued an early warning that increased rates of prolonged grief may be expected “considering the circumstances of many COVID-19 deaths [in which]… symptoms [of prolonged grief] are typically elevated when deaths are unexpected, traditional grief rituals (e.g., saying goodbye, viewing, and burial of the body) are absent, and physical social support is lacking.” Not only were older adults hit hard by COVID-19, many lost the social constructs that would normally ease the process of grieving. “So much has developed over the centuries to help us grieve—comforting rituals and support after death, for instance,” Simon adds. “But with COVID, bedside goodbyes and social support were off the table. If you can’t process the permanence of the loss, it is difficult to move forward.” Regardless of who experiences it, prolonged grief comes with increased health

risks. In Shear’s work, suicidality, heart trouble, cancer, and other physical ailments often accompany the condition’s emotional effects. A path to understanding

In spite of its debilitating consequences, prolonged grief is often an overlooked diagnosis. One of the first researchers to identify it as a distinct condition was sociologist Holly Prigerson during her postdoctoral career in the mid-1990s at what was then the Western Psychiatric Institute and Clinic at the University of Pittsburgh School of Medicine. “She noticed bereaved elderly adults who weren’t responding to treatment for depression,” says Shear. “Her statistics showed that grief symptoms loaded differently than those of depression. She came to me for treatment ideas.” Shear and Prigerson worked together to study this emerging syndrome, going into communities to talk with hospice and grief counselors. They layered in attachment theory research, too, which helps identify how strong the bonds are between the deceased and loved one. To improve how prolonged grief was identified and diagnosed, Prigerson and her colleagues established a 19-item inventory for screening patients. The inventory comprises a series of statements about grief-related thoughts and behaviors, such as “frequent intense feelings of anger or bitterness,” “belief that life is empty, meaningless, or unbearable because this person has died,” and “intense yearning or overwhelming desire to be with the person again.” Patients select one of five responses that range from “never” to “always.” When patients score above a certain threshold, they are considered to be at high risk for the condition and to require clinical care. Yet, before a physician can screen a patient, the patient must seek, or be guided to, help. “Many of our patients actually self-identify,” says Shear. “We have two-minute radio ads that people hear and recognize themselves.” Patients also are referred to Shear’s program by their primary care provider, a psychologist or psychiatrist, or a member of the clergy.

FLYNN LARSEN

“Prolonged grief generally presents with an inability to adapt to the loss,” Simon says. “You wake up and feel like your loss is brand new, over and over again.” In 2011, Simon and Shear, who also is the founder and director of the Center for Complicated Grief at Columbia University, co-authored a paper in Depression Anxiety on the condition and related bereavement issues. It explained that “grief can be complicated, much as wound-healing can be complicated,” with the intensity and duration of symptoms heightened and prolonged. Typical thoughts that prolonged grief sufferers experience, they wrote, include second-guessing, grief-judging, and catastrophizing the future. Behaviors include excessive avoidance, social withdrawal, substance use, and negative health behaviors. “The patients sometimes carry a lot of self-blame and have a tendency to repeat what-if scenarios, imagining alternative scenarios in which their loved one didn’t die,” says Shear. “This is all natural and even helpful early on, but eventually they must be able to set those feelings aside or figure out how to resolve them.” While there aren’t rigid rules as to who is more likely to experience such grief, Shear says that, in general, people who lose an identifying relationship—a parent, a child, a spouse—are more susceptible to the condition. If the separation was traumatic, such as a suicide or tragic accident, grief can be especially difficult. Women tend to seek treatment more often than men. “In clinical settings, over 80 percent of complicated grief patients are women,” says Shear. “The reason may be related to differences in the place of relationships in women’s lives.” In older adults, prolonged grief can affect as many as a quarter of those suffering a loss, according to a 2011 study, while a 2014 study in JAMA Psychiatry stated that about 9 percent of bereaved older women, defined as women over the age of 65, expe-

Not only were older adults hit hard by COVID-19, many lost the social constructs that would normally ease the process of grieving.

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Family members or other loved ones can also be the catalyst for seeking treatment. “We see cases where family or friends tell the patient that they can’t continue to support the patient’s behavior, and that it’s harming their relationship,” Shear says.

JOHN SOARES

Relearning happiness

Shear and others have determined that patients experiencing prolonged grief generally do not respond to the types of treatments traditionally used to address depression and PTSD, and they have worked to establish a separate protocol for treating Susan Block the condition. “The good news is that complicated grief patients have an immense capacity to heal and pull through,” Shear says. Simon agrees. “It’s not a quick process, but it also won’t require a decade of psychotherapy,” she says. Shear’s group developed a 16-week treatment protocol and tested it in three different National Institutes of Health-funded randomized controlled trials. The results were promising; on average, 70 percent of patients found relief from their grief. In general, their treatment protocol focuses on helping people accept the reality of the loss and restore their capacity for well-being. This is achieved by working in seven main areas: accepting grief, managing emotions, envisioning a positive future, strengthening relationships, narrating the story of the death, living with reminders, and connecting with memories. Patients have weekly meetings with a trained therapist and are given activities to complete between sessions. There also are targeted procedures in each area, such as working on a long-term goal, inviting a family member or a friend to a session, or visiting places that hold grief-triggering reminders of their loss.

“These are healing milestones that mark progress,” says Shear. The comfort of condolences

Despite the fact that prolonged grief is getting more recognition these days, there remains an overall lack of awareness of it in the medical community. Part of the problem, says Susan Block, an HMS professor of psychiatry and medicine and a member of the Department of Psychosocial Oncology and the Palliative Care Department at Dana-Farber Cancer Institute, is that grief is an issue that receives virtually no attention in medical school. “Grief is often considered outside the scope of practice by most physicians,” she says. Even medical students who receive some training in hospice and palliative care and are exposed to end-of-life issues have little exposure to grief, says Block. “Some students may hear about bereavement when they encounter a patient who dies, but prolonged grief isn’t understood or treated as a separate entity,” she says. “And while some physicians make a phone call, write a note, or attend a memorial service, there is rarely further contact after the

Patients experiencing prolonged grief generally do not respond to treatments traditionally used to address depression and PTSD.

death. The loss of the relationship with the physician may compound the family’s grief.” We do not have a system or a set of routine practices for caring for the bereaved, adds Block. This makes identifying a case of prolonged grief much less likely. “There should be a handoff from the deceased patient’s doctor to the survivor’s primary care doctor, but that really doesn’t happen,” says Block. “We need to consider this more at the systems level.” Simon would agree. “Ideally we would teach primary care physicians to check in about illness, mood, substance use, and basic functioning after a patient has lost a loved one,” she says. At Dana-Farber, where upwards of 2,500 patients die each year, the institution has taken steps to send a letter of sympathy to a member of each deceased patient’s family and has provided physicians with training on how to write such letters to survivors. “It’s the only system-wide effort I know of,” adds Block. “Hospices do a good job of following up with families after a death and serve as a model for everyone else.” Many physicians are grateful for guidance on how to construct such letters, says Block. “People, including doctors, often worry about saying the wrong thing to a bereaved person, or they aren’t aware of how incredibly powerful it can be to receive such a letter. I think that there is a growing recognition of the importance of this practice.” This may be especially true now. “The pandemic has at least brought grief, including prolonged grief, into a space of better awareness,” Block says, “but bereavement care in general has been inadequate throughout the pandemic because the health care system has been overwhelmed.” Light

For Jodi, time and professional help made a difference. She began to emerge from her cloud of grief after visiting an anxiety clinic where a practitioner diagnosed her state of prolonged grief and referred her to Shear’s structured program. Jodi made a full recovery and, in doing so, got her life back. Amanda Loudin is a writer based in Maryland. HARVARD MEDICINE | AU T U M N 202 1

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SPECIAL REPORT

I AGING I THOUGHTS FROM THE NIA DIRECTOR

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The head of the nation’s institute on aging research discusses investigating the biological intricacies of growing older Richard Hodes, MD ’71, is the director of the National Institute on Aging, one of the twentyseven institutes and centers of the National Institutes of Health. The NIA and its researchers take an encompassing scientific approach to understanding the nature of aging and investigating how to extend the number of healthy active years humans can enjoy. Established by the U.S. Congress in 1974, the NIA is the nexus of research on aging conducted throughout the Department of Health and Human Services. For twenty-eight years, the institute and the work of its scientists have been directed by Hodes. Harvard Medicine talked with Hodes earlier this year about research at the NIA, his interest in the field of aging research, and what aging, and healthy aging, mean. What follows is an edited version of that conversation.

Life’s Through Line

Harvard Medicine: Let’s start with some basics. How would you define aging?

INTERVIEW BY ANN MARIE MENTING

STEPHEN VOSS

Richard Hodes: There are several levels to the definition of aging.

There’s chronological age, which is measured by the passage of time and the changes that typically occur over time. There’s physiological aging, some of which has to do with appearance, and there’s functional aging. There’s also what is collectively known as aging HARVARD MEDICINE | AU T U M N 202 1

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I THOUGHTS FROM THE NIA DIRECTOR

processes. An example of aging processes is the so-called epigenetic clock of aging, which involves changes in gene expression over time. The concept of an epigenetic clock of aging developed because of experiments that followed individuals over time and monitored genetic changes in tissue such as peripheral blood. When analyzed, researchers found changes that correlated with age, but, interestingly, they also found that these changes varied by individual and by the tissue being monitored. The conclusion of a great many such analyses led to the realization that physiological aging differs from person to person. If you fine-tune the parameters of what aging means at a molecular level, you find that molecular variations also differ from person to person and that these interpersonal variations get greater with age. The relationship between what happens normally with age, with aging, and what is associated with pathology, disease, and unhealthy aging has led to an appreciation of how conditions or diseases that occur with increased frequency with age reflect some common ongoing processes that accelerate or function abnormally over time. The model for interpreting this is that age-related changes— aging—can be a risk factor for so many diseases and conditions. HM: Then what is healthy aging? RH: Healthy aging has meant, and still does mean, growing older

chronologically while remaining healthy, without disease or disability. To put it more positively, to grow older while maintaining independence and the ability to bounce back from medical, physical, or other types of stress. So, it’s chronologic age without disease and with the maximum preservation of function. The goal is to improve not simply life span but what is now referred to as health span: a high quality of life throughout life. HM: Does this evolving understanding of aging reflect the arc of research at NIA during your career there? RH: Absolutely. The technical, even conceptual, advances for how

we analyze aging and the causes of aging have yet to be fully appreciated. Just a few years ago, for instance, we couldn’t measure epigenetic changes in individual cells. We are now able to measure many changes in particular genes or proteins or the folding of proteins. However, we must be careful not to be too reductive; we must remember to bring our understanding back around to how the changes interact with other cellular and organic mechanisms. HM: Is the lens provided by the Baltimore Longitudinal Study on Aging useful when bringing a more systems-based view to lab-based discoveries?

RH: That study was launched fifty-plus years ago and was the

first really organized attempt to understand what happens with aging. Fundamentally, it allows us to consider how aging differs from disease and whether aging processes can be distinguished from disease. But it also provides an important distinction between the scientific approach of longitudinal versus cross-sectional studies. In the 32

The study is showing us that aging is not the same as disease and that disease is not inevitable.

1950s when it was just getting underway, studies of aging usually compared young people and old people. It was an understandable approach but one we now know is flawed. Who were in these studies? Well, the easiest way to find young volunteers was to approach students. And where were older people found? Nursing homes. So, a lot of the comparisons were of young healthy students and nursing home residents, a group that does not exhibit typical aging. The Baltimore Longitudinal Study on Aging, which is this country’s longest-running study on aging, was designed to intensely follow participants every year or every couple of years depending upon how old they are and what parameter is being studied. Participants stay at the research center for two or three days, have a series of tests done—blood, cognitive, physical functioning, and capacity. Later, brain imaging was added to the testing battery. Researchers begin to see what happens to individuals over time, and what determines who ages well by avoiding disease disability and who doesn’t. Everything I’ve just said about research progression from physiologic measures to more molecular ones and genetics and epigenetics has been paralleled in this longitudinal study. One of its great virtues is that early on researchers had the insight to store blood biological materials such as serum and peripheral blood cells. Now, when someone gets an idea about how something might change with age, they can, in many cases, do a retrospective longitudinal study and have twenty or thirty years of data available. Analyses of blood sugar levels, cholesterol levels, and, more recently, epigenetic and proteomic analyses using stored white blood cells can be retrospectively reconstructed. Researchers can also determine the changes that occur at increasingly fine molecular levels. The study is showing us that aging is not the same as disease and that disease is not inevitable. It also is allowing us to investigate what it is about individuals that’s responsible for their aging differently. Is it genetic? Is it environmental exposures? How much is modifiable? All these questions are part of our ongoing study of the three thousand or so participants. HM: Have you found any surprises? And have they led to interventions? RH: Well, there have been some surprises, and they vary over a

spectrum of characteristics with phenotypes. Take personality. HM: Personality?

RH: Yes! We haven’t talked about that, not as a molecular characteristic. It had long been proposed that personality changed with age. Again, a lot of this thinking was based on cross-sectional studies comparing young college students with old people in nursing homes. Real differences were found—and were attributed to age. But longitudinal studies found that, to a large degree, personality characteristics were constant over time. And they could be predictive of health outcomes—for example, optimism was associated with some positive health outcomes. Such associations were interesting because no one really had a sense of those before.

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Now, can you translate this insight into an intervention? Well, people have talked about whether you can compensate for what you understand about personality characteristics to improve our health behaviors. There was an appreciation that blood pressure was a risk factor for heart disease or stroke. Back when I was at HMS we were focused on, for example, the diastolic blood pressure as the real risk factor. Studies conducted in the past decades, however, have shown that the systolic pressure is critically important and that when you control blood pressure by bringing the systolic pressure down to levels defined by criteria determined through clinical trials, you decrease the probability of stroke, heart disease, and congestive heart failure. A study called SPRINT—and SPRINT MIND, a companion study to SPRINT—sought to determine whether a more aggressive control of blood pressure, taking people with a 140 systolic to 120 instead, could be beneficial and, if so, would it be beneficial if you were a 30-year-old, a 40-year-old, a 60-year-old, or an 80-year-old. That study was ended early for ethical reasons, but that was a very positive reason, for the study found that individuals who had their blood pressure controlled to a level of 120—remember 140 used to be a target—did much better. They survived better and they had fewer cardiovascular events, so the study was stopped. Because SPRINT ended, SPRINT MIND, which was investigating any changes in cognitive ability as a function of systolic pressure, also ended. When the available data from SPRINT MIND were analyzed, however, researchers found trends indicating that the probability of developing mild cognitive impairment, often an early stage of dementia or a precursor of dementia, decreased in people who had more vigorous control of their blood pressure. Because of this work, our recommendations for blood pressure control, not just in midlife but in older individuals, have changed. These changes have translated into public health recommendations that address other identified risk factors that could potentially make a difference in multiple diseases and conditions of aging. HM: These studies do point to the benefits of carefully evaluating medical measures, risk factors, and medications used in clinical practice. As you look ahead, do you see equally promising developments coming from research on novel therapeutics? RH: In fact, I can give you examples of how translation from more

molecular science to potentially promising interventions is already occurring. Some of the changes to the so-called pillars of aging, the components of the growing field of geroscience, pertain to the function of mitochondria, the energy-generating organelles in cells. In experimental models, studies have shown that interventions aimed at improving or sustaining mitochondrial function through aging make a difference in health and outcomes. Those findings are making their way into the first stages of experimental trials. Another example, which has received a lot of attention lately, is the phenomenon of cellular senescence.

Not so long ago, we thought cells were immortal. Now we know that’s not the case.

Not so long ago, relatively speaking, we thought cells were immortal. Now we know that’s not the case. The initial definition of senescence referred to replicative senescence—that the cells can’t divide anymore. Well, we’ve learned there’s much more that happens. Senescent cells are not passive; they have an abnormal phenotype that includes the production of a lot of inflammatory proteins. Genetic manipulation studies involving animal models have provided some very striking results. Specific manipulations of genetic material can selectively eliminate the small percentage of senescent cells that normally exist in an experimental animal. Doing so improves its musculoskeletal integrity, muscle mass, ability to run, cognitive function, function of multiple organs, and overall life-span expectancy. You can’t use those genetic procedures to directly eliminate senescent cells in humans, but as a corollary, drug interventions in animal models can eliminate the protective mechanisms that senescent cells have that keep them around. Drugs or drug combinations developed from therapeutics used in cancer regimens or used as anti-inflammatories have had a similar effect. If you give such drugs to test animals and selectively eliminate senescent cells, the animals live longer and have better-conserved function overall: brain function, cardiovascular function, musculoskeletal function. Studies of drugs that control senescent cells are in their early stages, with some now being taken into clinical trials. We don’t know if they’re going to be effective, but they do represent an example of translation from basic science. HM: It’s also an interesting example of how pervasive the effects of inflammation and inflammatory proteins can be in the body. It seems that changes in immune response are increasingly being associated with disease in aging. True? RH: Multiple changes occur in the immune system with aging. But

it’s an oversimplification to think that the immune system dampens with age, that it becomes less capable of responding. Changes to the immune system are specific to an individual, and they are not neutral. COVID-19 provides an example. The immune system in older adults may be less responsive to vaccines or other immunizations, but it may also respond to infection with hyper-responsiveness and inappropriate and prolonged inflammation. The strikingly selective vulnerability of older adults to morbidity and mortality with COVID has been linked to the hyperinflammatory response to the viral infection. But from COVID we are also learning other things about the effects disease can have on older individuals. These go beyond infection. What must be done to provide care to people who are older, who are institutionalized, who have had their social contacts modified? These are questions we are increasingly asking. Our strategy for caring for older adults will need to include helping them be more socially engaged and more connected with their health care system. It’s not just important to, for instance, gain knowledge of the clinical aspects of immune system function in older people, it’s also vital to promote and sustain the social, behavioral, and economic aspects of their lives. Ann Marie Menting is the editor of Harvard Medicine magazine. HARVARD MEDICINE | AU T U M N 202 1

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FIVE QUESTIONS

I CAROLINE SHAMU

A conversation with Caroline Shamu, HMS associate dean for research cores and technology, faculty director of the ICCBLongwood Screening Facility, assistant professor of biological chemistry and molecular pharmacology in the Blavatnik Institute at HMS, and assistant professor of radiology at Massachusetts General Hospital

What work goes on at the ICCB-Longwood Screening Facility at HMS?

Its main purpose is to screen large libraries of small molecules to determine their biological activity and whether they might be drug precursors and therefore useful in drug discovery projects. But the facility also allows us to screen large genomic libraries like RNAi libraries and CRISPR libraries to determine their effects on biological activity and function. This screening forms the basis of our translational work. What is the promise of this work?

Well, we do hope that we will find candidates that can be translated into drugs and therapies. But screening’s greatest value is that it illuminates biological activity and helps us understand function. Drug modulators allow you to study the dynamics of biological pathways. You can add a drug to switch a pathway on or off, then wash out the drug and reverse the action. How the pathway responds to such perturbations can help reveal how components of the pathway work together and whether a small molecule could be the basis for a drug. How did you end up in this field of research?

Outside of work, what fuels your imagination?

I love to cook and garden. I’ve been able to do a lot of that over the past year and a half! I am also involved in various local initiatives; I feel they ground me by keeping me connected to my community. My mom did volunteer work and was even on the planning commission in Kalamazoo, Michigan, where we lived. When my sons were young, I volunteered with their sports programs and at their school. Lately, I’ve been involved with efforts to build a community pool in the town we live in. I’ve also joined the League of Women Voters to support voting rights and voter education. It’s been really neat to meet women from different fields and different generations and to do this important activity for democracy. Which famous scientist or thinker would you like to have coffee with?

Shirley Tilghman. She’s a scholar, a renowned molecular biologist, an accomplished academic administrator, and a former president of Princeton University. It would be great to talk with her just to understand how she manages to balance it all. —Ekaterina Pesheva

JOHN SOARES

After I finished my postdoc training, I was thinking of going to industry. At that stage in my research career, I had set up a bunch of assay systems in different organisms— fruit flies, frog eggs, yeast, mammalian cells—so I felt I had a broad knowledge across many areas of biology. Screening was an emerging tool, and I thought it would be a good skill to gain. An opportunity opened at HMS, so I tried it out. Twenty years later, I’m still working in the field and in academe.

High-throughput screening is relevant to academic researchers, and I get to interact with colleagues in industry. It’s the best of both worlds.

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BACKSTORY

I MARIUS NYGAARD SMITH-PETERSEN, MD 1914

An alumnus’ insight revolutionized the surgical care of hip joint diseases

JOHN SOARES

JOHN SOARES (PHOTO); WARREN ANATOMICAL MUSEUM, CENTER FOR THE HISTORY OF MEDICINE, FRANCIS A. COUNTWAY LIBRARY OF MEDICINE

ARIUS NYGAARD SMITH-PETERSEN,

MD 1914, started pushing the orthopedic envelope as a Massachusetts General Hospital intern in 1916. After witnessing a bloody and brutal reduction of a congenital hip dislocation, he worked to develop a safer entry route into the hip joint. To sell the new technique to Mass General’s resistant orthopedic surgeons, SmithPetersen acquired a hip from the HMS anatomy laboratory, demonstrated his new method upon it, and brought it to the hospital as proof of his better way. Mass General orthopedics chief Elliott Brackett was impressed enough that he borrowed the hip, taking it to an American Orthopedic Association meeting, where it convinced several senior surgeons. Smith-Petersen, who emigrated with his family from Norway to Wisconsin in 1903, had a long-standing and prosperous Harvard career. After graduating from HMS, he entered a surgical internship at the Peter Bent Brigham Hospital under Harvey Cushing, MD 1895. In 1915, he followed Cushing to France with the American Ambulance Hospital. Once back in the United States, SmithPetersen moved to Mass General, eventually becoming chief of its orthopedic service in 1929. He was appointed an HMS clinical professor in orthopedics in 1935. Heralded as one of the most creative orthopedic surgeons of his time, Smith-Petersen developed treatments for diseases of the hip, particularly for joint reconstruction, that well outlived his days in the operating theater. His approach to hip joint reconstruction, or mold arthroplasty, began in 1923 with a piece of glass that he removed from a patient’s back.That glass, embedded for a year and surrounded by fibrous tissue lined by a synovial sac, inspired Smith-Petersen to develop a glass hemisphere that fit over the hip joint in order to similarly regenerate cartilage. The glass molds broke, but, encouraged by the results, Smith-Petersen kept testing materials, including the synthetic plastics Viscoloid and Bakelite and Pyrex glass. He finally found success with Vitallium, a cobalt-chrome alloy that was recommended to him by

his dentist,John Cooke. Smith-Petersen’s Vitallium mold arthroplasty proved effective and long-lasting, providing patients with pain relief and functional movement for up to 65 years after implantation, and became a preferred treatment for hip joint disease. Smith-Petersen retired from HMS and as Mass General’s orthopedics chief in 1946 but continued performing surgeries. In 1953, mere days before his death, SmithPetersen repaired the unresolved hip fracture of radio broadcaster Arthur Godfrey, who had been in pain for 20 years after an auto accident. The last clinic he conducted was in April 1953.Throughout a morning and an afternoon, he demonstrated case after case of successful arthroplasty operations, with patient after patient expressing gratitude for their palpable relief. —Dominic Hall

Some examples of the hip joint molds (middle and bottom rows, above) and reamers (top row) developed by Marius Nygaard Smith-Petersen.

Dominic Hall is curator of the Warren Anatomical Museum in the Center for the History of Medicine at the Francis A. Countway Library of Medicine. HARVARD MEDICINE | AU T U M N 202 1

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FEATURE

I BOOKSHELF

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A young man braves a watery escape from China and begins a new life as a physician in the United States by Kent Wong

It was Hong Kong’s promise of a better life, captured in the city’s bright lights, that kept author and physician Kent Wong committed to his plan to escape China, despite several setbacks.

LEE YIU TUNG/ISTOCK/GETTY IMAGES

OR SEVERAL DECADES, my American friends have encouraged me to write a book recounting my story of growing up in China and my multiple attempts to flee the Maoist regime. I hesitated. I am not trained as a writer. I’m a scientist, trained in medicine. So, I waited, believing that some other freedom swimmers would tell a story that mirrored mine. More than forty years have passed, and I am still waiting.… Many freedom swimmers who dreamed of a decent life—the same dream as mine—died on their journey. One of them [Curly]was a dear friend. He was with me in our first, failed attempt at escape. During his second attempt, he died in the sea…Should he be forgotten? My heart keeps telling me no.… In 2010, thirty-seven years after my friend’s death, I flew to Hong Kong. After a long ferry ride, I set foot, for the first time, on the “Beach of Bean Curd Rocks,” a unique feature of the island of Tung Ping Chau, in Mirs Bay. Freedom swimmers used to write on a large boulder there to mark their successful flight to freedom, but I found that the Hong Kong UNESCO Geopark now resided where the boulder once stood. Across the bay was a dark, jagged mountain range. I couldn’t discern which peak we traversed before descending to the coast where the People’s Liberation Army soldiers caught us during that first attempt, but I felt a chill run down my spine at the memory.…

Canton City was more than one hundred miles north of Hong Kong. To escape to Hong Kong, one needed to start somewhere closer to the coast. Starting midway between these two places would reduce the time spent crossing mountains and fields to about a week. Thanks to the senddown movement, many students had relocated to villages closer to Hong Kong than Canton, which were ideal for “lying under a pile of dirt.” Police heavily guarded the bus, ferry, and train stations in Canton City. All county roads leading to the Chinese coast north of Kowloon PeninHARVARD MEDICINE | AU T U M N 202 1

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BOOKSHELF

KSHELF

sula were punctuated by roadblocks and checkpoints guarded by militiamen. Back then, Chinese had to have permission to travel, and passing through all checkpoints required a valid travel document. Police and militiamen were good at checking documents, asking questions, and judging one’s appearance and expression. Fake travel documents were almost always used documents that had been bleached to erase the previous writing. But the bleaching left easily detectable marks on the paper.…

Previous escapees had pushed the seemingly impenetrable bushes outward, so we were able to fit our bodies inside the spaces created there. The stagnant air in these voids trapped the sun’s heat, steaming us. We kept motionless and speechless, and prayed for the sun to go away soon, but the sun didn’t bother listening. Finally, darkness came, and we slowly crawled out. 38

The road was dead, and we swiftly climbed the hill. The farther up we were, the more careless we became. We started to talk to make the climb easier and more pleasant. As we got deeper into the mountains, the vegetation became denser. The moon came out to illuminate the sky, but it was concealed from us by the mountains on both sides. I realized we were traversing the valley. Little creatures that crawled or jumped or flew were eager to irritate our skin; they ignored our scolding slaps. Our plan had been to reach the top of the mountain that first night. Like all other escapees, we planned to hide and rest during the day and cross the mountains during the night. But the dark-

COURTESY OF AUTHOR (MAP, FAMILY PHOTOS); MAKENOODLE/ISTOCK/GETTY IMAGES (ABOVE)

“Take out your travel documents!” a policeman on board announced. He started inspecting the documents of each passenger. He and his partner worked from the center of the aisle to the end and quickly got their first catch. The young man looked anxious as the younger policeman examined his paperwork. The younger policeman raised the travel document against the light and showed it to the older one, “Bleached?” The older policeman took a quick look and nodded.… It was my turn. “What’s the name of your village leader?” the older policeman asked as he inspected my document. “Comrade Lee, but we called him ‘One-Eye Dragon,’ ” I said. His eyes veered away from the paper and landed on my face. I looked him in the eye. He handed me the paper back and moved on. The younger policeman stared at [my sister] Ning, then quickly turned his head away and demanded, “Your document!” Ning obeyed. He looked it over and returned it to her, then moved to the next passenger. Once again, Ning had gotten a pass. She tended to have this kind of luck. As Mommy said, “Good looks and a nice dress go a long way.” I was sure that this time Ning’s looks, and not her clothes, had had something to do with it.…

The map above shows the three escape routes that Wong and others followed in their attempts to flee China. The “bean curd” rock formations, shown at right, are found along the shoreline around Hong Kong. A 1993 photo taken by the Xijiang River (below left) features Wong (wearing glasses), his young sons, and Qiang, a friend. The young Wong family (far right) gathered for this photo in the early 1950s.

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MAYA RUCINSKI-SZWEC

ness and the dense growth made this impossible.… We started to climb the hill in daylight. The cool temperature and the better visibility made all the difference, and soon we reached the top. The ridge was a strip of relatively flat ground with sparse vegetation. What a pleasant change! The strong mountain winds and full exposure to the punishing sun had driven away most of the moisture, and the insects that came with it. That was just fine with us.… We found a spot to rest and eat some of our food under a large tree surrounded by bushes. Unfortunately, black ants had beaten us to our meal. They had eaten through the plastic bags and buried themselves in the sea of sweet foods. “How can we get rid of them?” I asked. “Any idea?” “No way. They’re everywhere.” Curly was correct. “Then we have to eat them,” Ning said matter-of-factly.… “Do you believe in the Goddess of the Moon and her jade rabbit?” I asked Curly.… I felt love for the moon. She was never intrusive like the sun, which always tried to burn me into charcoal and flood me with my own sweat. Now her appearance calmed me as I traversed the mountains at night. Perhaps our ancestors felt the same way and did not want the shadows on her face deemed an imperfection. What could be more bittersweet than a lovely lady drinking the elixir of immortality to avoid an evil-minded pursuer here on earth, and so becoming the deity of the moon, living alone with a rabbit by her side, shown as shadows on the moon’s face, to remind the mortals on Earth? There she was, to watch over those of us who paid homage to her every year on the seventh day of the seventh month. Does she know she is guiding the freedom swimmers crossing the mountains at night? The next day, our third, a rainstorm hit. We tried, but failed, to shield ourselves under a large plastic tarp we’d brought along. We were soaked and freezing. We sat close to one another, trying to keep warm. Occasional thunder boomed directly over our heads, seeming much louder than the thunder we were used to at home. There was no need to get out from under our covering to retrieve water; instead, we merely stuck out our tongues to catch the voluminous raindrops rolling down our hair and faces. Far below us, through the curtain of the downpour, I saw peasants planting the paddies. It reminded me of how much I hated planting in the pouring rain—with an aching back, bloodsucking leeches, and bits of human waste floating around my legs!…

We were in a world of darkness and had been yearning for a better world for so long.

A sudden crash of lightning illuminated the mountains near us. How vulnerable we were! We must wait it out! Subtropical rain seldom lasts a whole day. Soon it stopped, and the sun came out, throwing two rainbows, one on top of the other, across the land. The raindrops had carried away the tiny dust particles suspended in the hot air to reveal the vivid details of the green leaves and colorful wildflowers around us. I tried to whistle to express my joyous state of mind, but I quickly gave it up, for the sound of my whistling destroyed the perfect harmony of nature. “Good,” I said. “Tomorrow will be a sunny day!” “How do you know?” Curly asked. “Because of the red sky late in the day.”… We couldn’t ask for a better ending to a dreadful day. We started our passage along the mountain ridges. The lingering twilight finally went away. Ahead of us was a bright light illuminating the mountain tops and radiated upward. “What’s that?” Ning exclaimed. “Can’t be the moon.” “It must be the neon lights of Hong Kong.” I was convinced of this. I recalled the photo from the Hong Kong magazine showing the intensely lit buildings jammed and layered up to the middle of the hills.… We were in a world of darkness and had been yearning for a better world for so long, and now, in front of us, the New World was giving us the first hint of things to come. We were moved. What could be a more dramatic welcome than lighting up half the sky for us?… Finally, after seven days, we saw the sea! Its blue water stretched to the far edge of a much lighter blue sky. We were speechless. How grand it was!. . . When we reached the foothills, it was dark. The foothills descended into a marsh, and we started across it, treading carefully to minimize the splashing sound of our footsteps. At the end of the marshland was the coast. With Curly leading and Ning in the middle, we slowly crawled toward the sea.… “Raise your hands,” said the soldier whose rifle was pointing at Curly. “Walk slowly. Keep your hands up. How many are you?” “I’m the only one,” Curly said as he walked toward the soldier. Ning and I kept still and held our breaths. Another flashlight swept across the field, to and fro, its beam approaching Ning and me. We turned our faces to the mud and waited for the inevitable. “Two more!” a second soldier shouted. “Stand up!” The game was over. Ning and I stood up and raised our hands. The soldiers tied our wrists using a long, thick rope and linked us together. “Sit down, and no talking!” the soldiers ordered.… Kent Wong, MD ’83, is a retired anesthesiologist in the Seattle area. This edited excerpt from his 2021 memoir, Swimming to Freedom: My Escape from China and the Cultural Revolution, appears with permission of the author and the publisher, Abrams Press. HARVARD MEDICINE | AU T U M N 202 1

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ALUMNI

I ROOTS I HILARY SIEBENS, MD ’80

Framing the Issue AS A CHILD, HILARY SIEBENS watched and cared

An interest in geriatric rehabilitation, and an understanding of how complex the care of older adults and people with disabilities could be, led Hilary Siebens to develop an integrated patient-care framework that is being adopted in clinical settings.

The idea of involving family in a patient’s care was born of personal experience. When Siebens was 13, her father died of cancer. His death caused significant suffering for her family, she says; her siblings and her mother had to cope with the emotional effects of their loss without help from medical professionals. “I think that experience was a defining influence.” As Siebens worked to finalize her patientcare framework, including conducting research that provided key insights for her model in older hospitalized patients, she also investigated the influence of mental models on organizational and systems behaviors and how these affect patient care. The latter work, she says,“clinched it for me. We need a broader mental model of patients and have health care address that.” After a period in Southern California, Siebens returned to Boston and added to her credentials, serving as an HMS lecturer in physical medicine and rehabilitation at Spaulding Rehabilitation Hospital and a

primary care geriatrician at Massachusetts General Hospital. She then headed back to California and began a push to fully develop her framework. The current version is now augmented by research-based self-care notebooks to help patients manage their own health care. Increasingly, her system of care is being adopted in clinical settings, including telehealth care management for individuals with Parkinson’s. Reflecting on the people who supported her idea along the way, Siebens is quick to call out two mentors at HMS: clinical physiologist Mark Altschule, MD ’32, and disability researcher Lisa Iezzoni, MD ’84. She hopes her work might be incorporated into medical school curricula, especially now, when concepts such as social determinants of health are being talked about commonly and broadly. —Susan Karcz

Hilary Siebens, MD ’80 | Principal, Siebens Patient Care Communications LLC | Founder, Siebens Domain Management Model

JOHN DAVIS; KELLY DAVIDSON (FACING PAGE)

for numerous animals and plants. Between college and medical school, she ran a clinic in a remote village in Ethiopia, where, by observing the people, she learned how to navigate an unfamiliar country and culture. When she entered clinical work, Siebens applied those early lessons in observation to create what has become her signature system for organizing care for patients. Siebens trained in internal medicine at The Johns Hopkins Hospital, where one of her key mentors, Arthur Siebens, or, as she knew him, Uncle Art, would help establish the Department of Physical Medicine and Rehabilitation. A geriatrics fellowship at HMS followed, sparking an interest in geriatric rehabilitation. A second residency, this time in physical medicine and rehabilitation, brought her an understanding of how complex the care of older adults and people with disabilities could be. Shortly after this training, Siebens began developing a framework she could use to care for her patients and, equally important, teach residents. The framework “looked at four domains: a patient’s medical issues, their cognitive and emotional makeup, their functioning and movement, and their physical and social environments, including family, home, and community.”

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STUDENT LIFE

I MMS

GRADUATES

Student Life Enas Mohamed BORN IN SUDAN and raised in the United Arab Emirates, Enas Mohamed grew up in “a very loving and caring family” that has supported her throughout her journey to pursue an education and a career. Although her path was different from that followed by many of the women in her family and community, “Mom always encouraged me to continue learning,” says Mohamed. “She said great women must complete their education and be independent.” Her mother’s best friend in the UAE is a neonatal pediatrician, and Mohamed’s uncle in Sudan is also a physician. “So during the school year I saw my mom’s friend, and on summer vacation I saw my uncle and his doctor friends. They told me it’s a long road and a tough road, but if you really love it, then go for it. Don’t give up.” She didn’t. She earned her MD at the University of Medical Sciences and Technology in Khartoum and did her rotations in the UAE, expecting to return to Sudan eventually and open a clinic. “In Sudan, there’s more to medicine than saving lives,” she says. “There is so much poverty, patients are not able to secure even minimum things. And women were treated differently, which I didn’t like.” She started thinking about how she might help address these larger issues. Her search led to the Master of Medical Sciences in Global Health Delivery program at HMS. After being accepted to the program, Mohamed began to research her thesis topic: female genital cutting. “The community thinks it increases a girl’s chances of marriage,” she says, but to observers “it’s one of the worst things you can ever imagine. Worse than seeing a patient with massive trauma.” Sudan banned the practice in April 2020. Mohamed graduated from the program this year, and her goal now is to become a woman’s advocate and human rights activist. She plans to start the work with the Sudanese immigrant community in Massachusetts. The Commonwealth also outlawed female genital cutting in 2020. But while the law may be on her side, thousands of years of culture are not. “They can outcast me easily if I don’t approach it the right way,” she says. “I need to gain the trust of the community first, and then slowly, slowly start talking about the harm of this practice.” She knows she has many years of work ahead of her, but keeps her mother’s advice in mind. “She always said to stay focused and be determined,” says Mohamed. “That’s how I got my medical degree, came to the U.S., and got into Harvard. I never give up.” —Elizabeth Gehrman

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MMS C GRADUATES

Rob Mancuso ROB MANCUSO IS NO STRANGER to second acts. When he was a teenager, he watched his older brother fall into using heroin and then get clean and earn a PhD. While still in his twenties, Mancuso married a woman and had three children before acknowledging that he was more attracted to men. His coming out was “very painful” at the time but ultimately strengthened his relationships with his family. And now, at 60, he has just earned a master’s in medical sciences in global health delivery (MMSc-GHD), after a successful career in sales and finance. Helping incarcerated opioid users secure employment and social services, the work he did for his thesis, was quite a change from his days as an executive. Though he had always enjoyed the sciences and initially was premed at Boston College, Mancuso ended up getting his MBA instead. “Making money was important to me,” he says, “because as a kid I had seen my mother putting things on layaway. She would send me to the stores to pay $3 here, $5 there, and I said I didn’t want to have to worry about things like that.” By his mid forties he’d tired of the corporate grind. He spent a few years teaching strategic management in Boston and in Parma, Italy, and then got involved in philanthropy. “I tried golfing and boating after I retired, but it was not at all fulfilling,” he says. Seeking a new challenge, Mancuso began taking courses at Harvard and got involved with Partners In Health, where he met the nonprofit’s co-founder Paul Farmer, MD ’88 PhD ’90, the Kolokotrones University Professor of Global Health and Social Medicine, and Joia Mukherjee, an associate professor in the Department of Global Health and Social Medicine in the Blavatnik Institute at HMS. From them, Mancuso learned of the MMSc program at HMS. “I fell in love with it. These people were so compassionate, trying to help in the most challenged areas of the world,” he says of Farmer and the other three professors teaching a global health course at Harvard Extension School. “I thought, this level of commitment is exceptional.” He chose his thesis topic partly in memory of his brother, who, after putting drugs behind him and achieving academic success, died in a car accident at age 30. Mancuso also witnessed the devastation drug use can have during his daily run past the Pine Street Inn and Boston Medical Center. He’s not quite sure what he wants to do with his new degree—perhaps ultimately work to influence policy—but he plans to start by mentoring young trauma survivors in Chelsea, Massachusetts. “I want to be with people,” he says, “not in a boardroom. Any little bit I can do will help.” —Elizabeth Gehrman

HARVARD MEDICINE | AU T U M N 202 1

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Ana Cristina Sedas

KELLY DAVIDSON (THIS AND FACING PAGE)

IN 2018, DURING ONE OF THE EN MASSE migra-

tions to the United States by people from Central America, Ana Cristina Sedas volunteered as a physician at camps in Mexico City and Tijuana, Mexico. At one of these camps, she met a 5-year-old boy from Honduras who was wearing Mickey Mouse Crocs and clinging to his mother. “I imagined my nephew of the same age walking across four countries,” says Sedas, who recently earned a master’s in medical sciences in global health delivery (MMScGHD) at HMS. She knew that if this boy or his mother had fallen ill during their perilous and arduous journey, they would have had no access to health care. “Why is this allowed?” Sedas recalls asking herself. Born in Pittsburgh and brought up in Monterrey, Mexico, Sedas is linked to two cultures: her mother is a native of Mexico and her father hails from the United States. She holds dual citizenship and travels frequently between the two countries. Before pursuing her master’s, Sedas earned a medical degree at the Monterrey Institute of Technology and Higher Education and completed a rotation at the Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital. She also had served as a health promoter for an initiative of the Mexican Consulate General in Boston aimed at improving access to health care and health literacy among migrants primarily from Mexico. This appointment came at a fraught time, just after the 2016 U.S. presidential election, when raids and deportations by U.S. Immigration and Customs Enforcement were increasing, causing many migrants to avoid services and aid. Sedas wondered how she could help people feel safe enough to seek available health services. A chance encounter with a couple from Mexico at a bus stop in Boston led to an answer. Their daughter was in the MMScGHD program, and Sedas soon met her and others in the program. From her new friends, Sedas learned of a health care model in which physician and patient travel the health care system in tandem, staying

together until the patient’s health concern is resolved. Using that model, Sedas built a successful program for the consulate and the migrant populations it serves. Sedas says the HMS program gave her the know-how and tools to change how migration health is addressed, skills she will bring to her new position as a consultant on

migration health at the World Health Organization. She is making it her mission to show that health and equal access to care is a universal right, one reserved for migrant populations, too. To do policy work, she says, it’s helpful “to know there is a 5-year-old boy walking.” —Bobbie Collins

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MMS C GRADUATES

Terence Bowie Mark PAPUA NEW GUINEA IS A COUNTRY that struggles with poverty, corruption, and, according to 2018 numbers, a doctorpatient ratio of 1 to 14,000. But it is also a country with people who are deeply involved in bettering the lives of its residents. One such person is Terence Bowie Mark. Mark, who earned a master’s in medical sciences in global health delivery (MMSc-GHD) this year, was placed on the path to making a difference early. His mother was able to carefully budget the family income to purchase a TV so her son could stay somewhat removed from their “rough neighborhood” in the capital, Port Moresby. “She introduced me to the alphabet by encouraging me to watch Sesame Street. Those furry characters are a force of nature!” She also put Mark through English kindergarten and made sure he obtained a public library card. “My mom saw education as the pathway to a better existence,” he says. Mark “felt a calling” toward medicine while attending a Christian youth conference, and after receiving his MD from the University of Papua New Guinea, began rotations in both Port Moresby and the rural highlands, at times sleeping in the wards because the staff was so overburdened. “It was very traumatic,” he says. “There was no hope of providing timely care to those who needed it.” After instituting a new triage system that turned around the emergency and outpatient departments in the Kavieng General Hospital in the nation’s New Ireland Province, Mark finally had time to step back and consider his future. Through online searches he discovered Partners In Health, a group he felt was “providing the highest quality of care to the most desperate, marginalized communities in the world.” He began the master’s program last year and, for his thesis, he and a colleague in Papua New Guinea started Neighbour Health, a nonprofit that educates and provides preventive health care to rural Indigenous households. Mark hopes the organization will act as a springboard, giving him a platform for proof of concept for innovations and ultimately the clout to influence policy. Tackling his country’s seemingly insurmountable problems, he says, is his mission. “I told God, if you give me the opportunity to get such knowledge and experience as a kid from this island, I will go back and help your people,” he says. “He has kept his part.” —Elizabeth Gehrman

KELLY DAVIDSON

HARVARD MEDICINE | AU T U M N 202 1

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I NEWS

Varnel Antoine announces his residency in urologic surgery at Brigham and Women’s Hospital outside the entrance to the original Peter Bent Brigham Hospital building.

COURTESY OF VARNEL ANTOINE

ALUMNI

Match List 2021 HARVARD MEDICINE | AU T U M N 202 1

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NEWS

Match List 2020

ANESTHESIOLOGY Uday Agrawal Massachusetts General Hospital Katherine Redfield Chan Brigham and Women’s Hospital Ashwini Joshi Massachusetts General Hospital

Brenna Nelsen Stanford University Programs

Anthony TuckerBartley Massachusetts General Hospital

DERMATOLOGY Sepideh Ashrafzadeh Massachusetts General Hospital Amy Blum Duke University Medical Center Ai-Tram Bui Stanford University Programs

Graduates (left to right) Mark Zaki, William Murphy, Samantha Harris, Kelly McFarlane, and Vartan Pahalyants gathered for a post-vaccination celebration of their residency announcements. Perched between Harris and McFarlane is an unidentified canine— residency plans unknown.

Samantha Guhan Northwestern University McGaw Medical Center Lisa Guo Massachusetts General Hospital Ruby Kwak University of Miami/ Jackson Health System Devon McMahon Hospital of the University of Pennsylvania Danna Moustafa Massachusetts General Hospital

William Murphy Barnes-Jewish Hospital Vartan Pahalyants New York University Grossman School of Medicine Mack Su Massachusetts General Hospital Zizi Yu Boston University Medical Center

EMERGENCY MEDICINE Baturay Aydemir Western Michigan University Charles Brower University of Cincinnati Medical Center Taylor Brown Beth Israel Deaconess Medical Center Thomas Church Riverside Community Hospital Anna Fang Boston University Medical Center

Zachary Johannesson Ohio State University Medical Center Nelson Malone Johns Hopkins Hospital Bridget Matsas Madigan Army Medical Center Conor Narovec Ohio State University Medical Center Jamaji NwanajiEnwerem Emory University School of Medicine

COURTESY OF MARK ZAKI, ET AL.

Juan Macias University of Utah Health, Salt Lake City

Hannah Scott Stanford University Programs

HARVARD MEDICINE | AU T U M N 202 1

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Jordan Petersen Alameda Health Systems-Highland Hospital Asmaa Rimawi University of Michigan Hospitals Morgan Sehdev Massachusetts General Hospital

Chase Marso Massachusetts General Hospital

Jennifer Ge Brigham and Women’s Hospital

Larisa Shagabayeva University of Miami/ Jackson Health System

Jakub Glowala Northwestern University McGaw Medical Center

Natalie Williams University of Texas Southwestern Medical School

Sharon Grossman Massachusetts General Hospital

FAMILY MEDICINE Jacob ArellanoAnderson University of California San Francisco

Aditya Achanta Massachusetts General Hospital

Katherine McDaniel Boston University Medical Center

Titilayo Afolabi Massachusetts General Hospital

Alma Oñate Munoz Greater Lawrence Family Health Center

Stephanie Alden Johns Hopkins Hospital

Nikolai Renedo Maine Medical Center

Erik Bao University of California San Francisco

Tiantian White Oregon Health and Science University

Jonathan Boiarsky UCLA Medical Center

GENERAL SURGERY

Alexis Coolidge Massachusetts General Hospital

Rachael Acker Hospital of the University of Pennsylvania

COURTESY OF ANGEL REYES

INTERNAL MEDICINE

Richard Ebright Massachusetts General Hospital

James Agolia Stanford University Programs

Ahmed Elnaiem Brigham and Women’s Hospital

Huma Baig Beth Israel Deaconess Medical Center

Kirby Erlandson New York University Grossman School of Medicine

Denston Carey New York University Grossman School of Medicine

Bryn Falahee Brigham and Women’s Hospital

Nicholas DeStefino Beth Israel Deaconess Medical Center

Michael Fuchs University of California San Francisco

Samantha Harris Barnes-Jewish Hospital Melody Huang Massachusetts General Hospital Garret Johnson Duke University Medical Center Revanth Kosaraju UCLA Medical Center Jonathan Kusner Duke University Medical Center Nicholas Kwok Cedars-Sinai Medical Center Geetika Mehra University of Chicago Medical Center Mahan Nekoui Massachusetts General Hospital Sarah Onorato Brigham and Women’s Hospital David Reshef Brigham and Women’s Hospital Abigail Schiff Brigham and Women’s Hospital Helen Shang UCLA Medical Center

Haziq Siddiqi University of California San Francisco Eriene-Heidi Sidhom Massachusetts General Hospital

Angel Reyes (left) and Hilary Dolstad, MD ’20, his girlfriend, share news of his residency in orthopedic surgery at Massachusetts General Hospital.

Xiaoling Yu Hospital of the University of Pennsylvania

Gabriella Herrera University of California San Francisco

Sohail Zahid New York University Grossman School of Medicine

Ethan Manelin Brigham and Women’s Hospital

Mariame Sylla Brigham and Women’s Hospital

Mike Zhai Brigham and Women’s Hospital

Maria Thomas Brigham and Women’s Hospital

Amy Zheng Massachusetts General Hospital

Matthew Townsend Duke University Medical Center

Joyce Zhou Massachusetts General Hospital

Kruti Vora Massachusetts General Hospital Chen Wei Stanford University Programs Constance Wu University of California San Francisco

Hema Pingali Brigham and Women’s Hospital Erin Plews-Ogan Massachusetts General Hospital

NEUROLOGICAL SURGERY

MEDICINE-PRIMARY

David Cote University of Southern California

Michael Alcala Brigham and Women’s Hospital

Mark Zaki University of Michigan Hospitals

Daniel Gonzalez UCLA Medical Center

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NEWS

ORAL AND MAXILLOFACIAL SURGERY Andrew Emery Massachusetts General Hospital Yisi Ji Massachusetts General Hospital

ORTHOPEDIC SURGERY Troy Amen Hospital for Special Surgery Jonathan Franco Massachusetts General Hospital Kelly McFarlane Stanford University Programs

Allen Zhou captures for posterity the news of his residency in otolaryngology at Massachusetts Eye and Ear.

NEUROLOGY Iyas Daghlas University of California San Francisco Linda Xu Hospital of the University of Pennsylvania

OBSTETRICS AND GYNECOLOGY Elizabeth Byrne Brigham and Women’s Hospital Ann Cathcart Oregon Health and Science University Kathleen Koenigs Brigham and Women’s Hospital

Anabel Starosta Yale-New Haven Hospital

Sonya Ye Naval Medical Center, San Diego

OPHTHALMOLOGY Kaitlyn Brettin Wills Eye Hospital Enchi Chang Massachusetts Eye and Ear James Harris Massachusetts Eye and Ear Chloe Li Columbia University Harkness Sachin Patel University of California San Francisco

Michael Seward Mayo Clinic School of Graduate Medical Education

Andrew Parsons Boston Children’s Hospital

PATHOLOGY

PLASTIC SURGERY

Chen Lossos Johns Hopkins Hospital

Ryoko Hamaguchi Brigham and Women’s Hospital

PEDIATRIC PSYCHIATRY

Abra Shen University of Washington Affiliated Hospitals

Timothy McGinnis Johns Hopkins Hospital

PEDIATRICS Patricia Corona Rush University Medical Center David Gootenberg Boston Children’s Hospital Julia Hiserodt Duke University Medical Center Jane Irwin Boston Children’s Hospital

Nathan Varady Hospital for Special Surgery

Aditya Kalluri Boston Children’s Hospital

Evan Zheng Massachusetts General Hospital

Katherine Kester Children’s Hospital of Philadelphia

OTOLARYNGOLOGY

Cara Lachtrupp Boston Children’s Hospital

John Ceremsak Vanderbilt University Medical Center Manuela von Sneidern New York University Grossman School of Medicine Chloe Warinner Massachusetts Eye and Ear Rachel Weitzman New YorkPresbyterian Hospital/Columbia and Cornell

Jessica Laird Boston Children’s Hospital Carlton Lawrence Icahn School of Medicine at Mount Sinai Michelle Lee University of California San Francisco Ruchit Nagar Yale-New Haven Hospital

PSYCHIATRY Sun Fletcher Cambridge Health Alliance Anthony Jang UCLA Semel Institute for Neuroscience Benjamin Landwersiek Cambridge Health Alliance Ali Raza Brigham and Women’s Hospital Lucas Wittman Brigham and Women’s Hospital

Regina Parker Tamposi Walter Reed National Military Medical Center Anna Zhao Brigham and Women’s Hospital

THORACIC SURGERY Sarah Nisivaco Northwestern University McGaw Medical Center

UROLOGY Varnel Antoine Brigham and Women’s Hospital Francisco Ramos University of Texas Health Science Center at San Antonio Chanan Reitblat University of Michigan Medical Center

OTHER Jacob Donoghue Beacon Biosignals

RADIATION ONCOLOGY Edward Dee Memorial SloanKettering Thomas Howard Massachusetts General Hospital Yuzhong Meng Memorial SloanKettering Leah Thompson Massachusetts General Hospital

RADIOLOGY Corbin Ester Duke University Medical Center

Senan Ebrahim Delfina Mark Kalinich Watershed Informatics Suan Tuang Eventide Asset Management Adrian Veres Harvard University Da Yang Artist Institutions listed represent categorical residency matches and their locations. Locations of preliminary or transitional programs are not included.

COURTESY OF ALLEN ZHOU

Natalie Posever Beth Israel Deaconess Medical Center

Isabelle Wijangco University of California San Francisco

Angel Reyes Massachusetts General Hospital

Allen Zhou Massachusetts Eye and Ear

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ALL IMAGES COURTESY OF THE CENTER FOR THE HISTORY OF MEDICINE, FRANCIS A. COUNTWAY LIBRARY OF MEDICINE

ROUNDS ALUMNI ROUNDS

DETAILS, UPDATES, AND OBSERVATIONS FROM ALUMNI

Fuller Albright, a physician and endocrinologist at Massachusetts General Hospital, made significant contributions to his field, including elucidating the major hormonal functions of the adrenal cortex.

Which of your clinical rotations during medical school made the greatest impression on you? HARVARD MEDICINE | AU T U M N 202 1

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ROUNDS

John D. Bullock, MD ’68

Surgery at the Beth Israel with Bill Silen. I knew I wanted to become an ophthalmologist, but I loved watching him. He was a beautiful surgeon. When he opened the belly or the neck, it looked like photographs from an anatomy text. I tried to emulate him when I was doing all my operations. I would tell my fellows, “You can’t rush perfection.” That’s what I learned from him. In practice for 25 years, I performed more than 10,000 operations and was never sued. Thank you, Bill! John B. Livingstone, MD ’58

Four of us stood on rounds during our clinical rotation in internal medicine in 1957. We were listening to a visiting expert in infectious diseases when he proclaimed: “Gentlemen and lady, listen up, as I’m going to make a biblical statement: The viruses shall inherit the earth.” Although I felt helplessly vulnerable and then curious about my own reaction, it took the next 64 years, including witnessing the recent burnout of clinicians caring for COVID patients, for me to fully embrace the truth of what he said. My response to a profound statement made on a clinical rotation was a trailhead for my medical teaching and research career, including co-authoring a textbook on the power of relationships in health care in 2016. Sheila Hafter Gray, MD ’58

My third-year medicine rotation at Boston City Hospital—that’s where I learned how to be a physician. Thomas Bettman, MD ’69

Anesthesia at the Brigham under Leroy Vandam. First day on the rotation I did not understand the difference between green and blue gas cylinders. Catastrophe was averted by the watchful eye of Vandam. Afterward we had a long, calm, insightful discussion of errors in medicine, especially related to supervising less-experienced people, but also recognizing the key roles of humility, personal vigilance, and mastery of information related to clinical care. Readers may find the Closed Claim Project, under the aegis of the American Society of Anesthesiologists, to be relevant here. 50

Elizabeth Wise, MD ’78

Internal medicine at Peter Bent Brigham, where we learned the history of the coronary care unit’s “Lown chairs,” which were recliners for patients born from Bernard Lown’s insight that patients should not in fact be kept on strict bed rest after heart attacks. So he got them up, and in so doing reduced the number of pulmonary emboli. Christopher Smith, MD ’89

The intense growth of my medicine clerkship stands out in my memory as a remarkable life-changing experience. We learned

William Silen (second from left), sits with Tariro Makadzange, MD ’05 (left to right), Kristofer CharltonOuw, MD ’02, and Alfredo QuiñonesHinojosa, MD ’99.

to draw blood tests on our patients at the West Roxbury VA before morning rounds, made gram stains, followed our patients to the OR, and nervously presented their case histories in front of peers, resident teams, and professors. I recall the thrill of poring over our patients’ medical records searching for clues to their illnesses and reading Harrison’s Principles of Internal Medicine late at night in the Brigham library. We formed bonds with our patients, who tolerated our earnest but awkward efforts. And most important, we were nurtured by amazing clinicians, including Sanjiv Gupta (charming, witty,

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opened the stenotic mitral valve with his finger he said to me, “Come here and [put] your finger in the aurical.” I could feel the mitral valve open and close on my finger. How’s that for medical drama? Samuel (Bob) Snodgrass, MD ’63

MGH medicine, fourth year. I worked hard and did many procedures, which clearly needed to be done. Barry Zitin, MD ’73

Surgery at MGH. It was in the days when we worked every other night and every other weekend, so we had two months of total immersion. I had a dream team of house staff: Andy Warshaw, MD ’63, Jim May, Cary Akins, MD ’70, and Arlan (Skip) Fuller. They were terrific teachers and physicians—smart, dedicated, caring. I was never so tired or so engaged. When I returned to the outside world, I realized that I missed that world and missed getting to know the patients better. I ended up with a very fulfilling career in psychiatry. Bruce Barnett, MD ’75

and always ready with an unlimited supply of clinical pearls) and Dan Federman, MD ’53, the kindest and most inspirational teacher I have ever had. Those three months were the centerpiece of my HMS education. They instilled in me a foundational set of guiding principles and a deep passion for the practice of medicine that motivate and sustain me to this day. Don Dickerson, MD ’57

During my senior year surgery rotation at the Brigham I rotated through the cardiac surgery department under Dwight Harken. This was before the pump. After he had

Among my clear memories of so many superb rotations a few stand out. Harvard’s Introduction to the Physical Examination taught me to consider first my patient’s chief complaint. That has been the foundation of my clinical practice ever since. Oddly, perhaps, the elective rotation that introduced a small group of my class to the phenomenon of hypnosis has been useful in my clinical and personal life to this day.

Daniel Federman (top, left), an endocrinologist whose work was pivotal to the development of the field of genetic endocrinology, was also known as a leader in medical education. Surgeon Dwight Harkin (below, left) worked at Brigham and Women’s Hospital and was wellrecognized for the many advances in cardiac surgery he pioneered.

Christopher Baker, MD ’74

In my third year, I spent two months with the liver transplant team at Addenbrooke’s Hospital in Cambridge, England, working with Maurice Slapak, who had been my preclinical mentor at Boston City Hospital. In addition to solidifying my decision to pursue general surgery as a career, it helped me crystallize my attitudes toward medical ethics. David Sachar, MD ’63

Outpatient clinic when I correctly diagnosed a young housewife who complained of fatigue with myasthenia gravis. On her third visit, she mentioned having double vision. She taught me the importance of listening carefully to patients. They are telling you the diagnosis! Dick Peinert, MD ’73

Radiation therapy, one of the few rotations where the students were treated like colleagues. Things are probably different now, but back in the day a lot of professors really went out of their way to “teach” us how little we knew versus teaching us what we needed to know. Sam Hellman, Bill Shipley, MD ’66, and Tony Piro (later a colleague when I went into practice) were terrific teachers and kind men. Edmund Lee, MD ’96

Psychiatry. The consequence of emotional trauma was difficult to witness. However, that experience has informed my practice of dermatology on a regular basis.

Calie Santana, MD ’02

Elizabeth Dreesen, MD ’87

My pediatrics rotation. I met children with cancer whose parents couldn’t visit them from New Hampshire due to cost. Patients with asthma whose caretakers smoked around them. The curriculum didn’t reference or unpack social determinants of health, but the hidden curriculum was undeniable. I took these cases home with me every night and tried to think of structural upstream solutions without having the vocabulary. It was eye-opening and a bit traumatic. I decided I couldn’t do peds as a career.

The frank brutality of my surgical clerkship. Every other night. Rounds at 4 a.m. before the T started running. I asked for parking so that the other woman student and I could safely reach the hospital in the dark. The male students cried discrimination when we got one. Still, every day for two months, my car safely ferried one of us to and from the hospital. I liked surgery, but the gratuitous nastiness of the clerkship sent me to OB for a year, before I lateraled to surgery in a nicer place.

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ROUNDS

George Hill, MD ’57

Medicine, at the Boston City Hospital. William Castle, MD 1921, and his faculty gave full responsibility for each medical ward, about thirty patients, to an intern and his fourth-year medical student. The two of us saw and initiated treatment for two patients on the ward who developed a femoral embolus and a stroke. I assisted in a gastrectomy for one of my patients. I made a diagnosis that had been missed in the hematology clinic and I did a pericardial tap. An awesome time.

Simeon Locke (near right) was a neurologist and a scholar who wrote about consciousness, neurolinguistics, and schizophrenia. Anesthesiologist Leroy Vandam (far right) made significant contributions to his chosen specialty throughout his career at HMS.

George Lewinnek, MD ’67

My most vivid memories are of three months of general medicine in my third year, which is strange, given that I always had a surgical bent and became an orthopedic surgeon. I enjoyed the diagnostic challenges and the applied physiology. I also remember getting into trouble twice, in both cases overstepping my boundaries trying to protect patients. Harold Sox, MD ’66

Pediatrics. I loved surgery, my first rotation, but pediatrics immersed me in the world of clinical reasoning, and I was hooked for life. In the end, I became an internist. Jan Polissar, MD ’61

Public health lectures by David Rutstein. He pointed out that the greatest effects on public health are not always made by physicians. I believe my classmate, Mike Lane, MD ’61, who spearheaded the eradication of smallpox, saved more lives than any other physician in the modern world. Jim Adelstein, MD ’53

Fuller Albright, MD ’24, was quite disabled by Parkinson’s disease, for which there was then no good treatment. He traveled to and from MGH in a vintage two-door sedan. The medical student of the month was his driver—picking him up at home in the morning and returning him in the evening. During the day, I shadowed him when he was seeing patients, leading discussions in the endocrine and bone clinics, in lab meetings, or making rounds. I learned 52

much from him about endocrinology and human resilience. Michael Rasminsky, MD ’64

HMS third-year sessions with Simeon Locke at Boston City Hospital propelled me toward clinical neurology/neuroscience. Years later, at lunch with him and a mutual colleague in Montreal I told Simeon that my decision to become a neurologist had been largely influenced by that initial exposure to him. He turned beet red, stammered something unintelligible, and changed the subject. I resolved that the only possible

thanks for that early experience was to be the best teacher possible with the students under my tutelage. Martin Prince, MD ’85

Surgery was amazing. Especially the surgical ER rotation at MGH, where we were sewing up lacerations and doing real frontline patient interactions. John Carmody, MD ’65

Third-year clinical rotation in surgery at MGH. I had really struggled my first two years with basic science and was scared to

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Kathy Glatter, MD ’93

Laurie Green, MD ’76

I really enjoyed doing a plastic surgery elective at MGH with a well-known, successful surgeon there. He had gold-plated instruments, which really impressed me, and he let me tap the hammer to break the patient’s nose that he was reshaping.

General surgery, with Frannie (Francis) Moore, MD ’39. He was a larger than life Renaissance figure who shared my interest in medical history. Yet he hadn’t quite processed the onslaught of female medical students at a time when there were no female surgical trainees. For the first time, I saw the benefits of military training: rigor, devotion to duty, precision, stamina.

Tamara Fountain, MD ’88

Psychiatry was my first rotation, so perhaps there was some bias in my memory there. It was the first time I realized, with horrifying clarity, that the mind can get sick just like any other organ or body system. A person with a bad heart is still the same person we always knew. A person with mental illness challenges the essence of how we think of them as a person. Perhaps this is what I found so destabilizing about this clinical experience, and apparently so memorable as well.

Mary Flowers, MD ’78

My residency at Brockton Hospital. My first night on call I had a veteran who ended his life by jumping from a second story window. William Goodson, MD ’71

Surgery clerkship with William Silen, who demanded more of himself than from us, and the chief resident, Gary Manchester, MD ’64, who was excited about his work and taught us with the same enthusiasm. He had a reverence for clinical care, and he went out of his way to be certain we learned from the instructive and unusual situations.

Karen Singer, MD ’77

death that first morning, when two of my classmates and I met with our teaching resident. He introduced us to our very first real patient. “Do an H & P, I’ll be back in thirty.” He began by asking my two colleagues very basic questions, and neither had a clue about Dx or Rx. I could not believe it. “John, tell us about our patient.” I knew then I belonged at HMS. Kara Wong Ramsey, MD ’09

I did not speak any Spanish when I enrolled in rural medicine in Latin America as a fourth-year med student. With only one month of Spanish lessons at the med school, I was placed in Hospital Nacional de Niños in Costa Rica. It was a humbling experience as I struggled to understand and participate in the conversations in Spanish going on around me. I reflected on how non-English speakers must feel in the U.S. medical system and the importance of diversity in physician training and recruitment.

Plastic surgery. I thought anything was possible being a plastic surgeon. I performed my first surgery, an excision of a lipoma. Not a big deal later, but it sure was then. The patient was perfect, and the operation went well. Gave me confidence. I saw remarkable surgeries, breast reconstructions, facial reconstructions after trauma, abdominoplasties. I saw the difference one could make for so many people.

Charles Janeway

Karl Singer, MD ’67

The course I remember the most was a one-month epidemiology elective taught by David Poskanzer, MD ’54, a neurologist at MGH who had been in the Epidemic Intelligence Service at CDC. I have been using many of the lessons I learned in that course over the past seven months of the pandemic. I also remember our final meeting, when David took us all to dinner at Locke-Ober. Peter Zawadsky Jr., MD ’68

My pediatrics rotation at Boston Children’s Hospital was probably my most memorable. The teaching staff was very motivated to educate medical students. Physician-in-chief Charles Janeway was an excellent advisor and helped me with my career development. HARVARD MEDICINE | AU T U M N 202 1

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ROUNDS

Paul Russell

seemed to have much purpose, his stories would have been science fiction only a few years earlier. Lessons of Elio Raviola applied in the OR, functional anatomy—it was exciting. My interests changed but I’ve forever sought tangible results: ones we can see, touch, measure in the now. Robert Colvin, MD ’68

Surgery at MGH, an afternoon two-hour small group seminar with the chief of surgery, Paul Russell. Robin Smith, MD ’88

I remember being on rounds at the Brigham and the senior resident asking questions Socratic style. When it was my turn to answer, I replied that I did not know but that I would be happy to learn if he wanted to teach me. He stopped rounds, and I thought I was done. Then he said, “That is the smartest thing I’ve ever heard a Harvard Medical student say. The first thing you need to know is what you don’t know.” That has stuck with me throughout my career. Steven Swerdlow, MD ’75

Marvin Bittner, MD ’76

Psychiatry at Mass Mental Health Center, in Spring 1974, was a rich blend of education and clinical service, and it incorporated a wide range of viewpoints from the frontiers of psychopharmacology to a psychoanalyst who eschewed any drug therapy. The clinical presentations of the patients were dramatic, and the didactic material utterly engaging. The insights of the faculty complemented their unwavering commitment to teaching. That experience set a high bar for clinical rotations. Joseph Savino, MD ’84

The rotation was surgery, but the impression came from role models. I had dinner at the home of a senior cardiothoracic surgeon. Both at the hospital and at home, his life 54

You might think it was my pathology rotation and getting to go to the great William Meissner’s home that was special, but it was more the moments dripping with sweat while sewing up a gash in the MGH ER, the moments dripping sweat on a patient in cardiology because I was having fevers but you were not supposed to call in sick back then, or the time I asked not to be sent to review a massive set of charts on a patient with an obvious hip fracture. That wasn’t my idea of learning orthopedics. Priscilla Slanetz, MD ’91

I became a radiologist not because of my radiology rotation, but because of Stanley Wyman, MD ’39, an esteemed diagnostician who could tell me everything about the patients I was following on the medical wards just by looking at a plain radiograph of the chest or abdomen. Back in those days, cross-sectional imaging with CT was used only sparingly. The visits to the radiology

reading room made me aspire to become an expert at interpreting “shadows” on all imaging modalities. Suzanne Boulter, MD ’68

Boston City Hospital was an incredible environment to learn about the care of patients prior to the enactment of Medicare. Ambulances brought the sickest, the poorest, and people of color to Boston City where a dedicated and distinguished group of house staff and attendings provided them all with topnotch care. As a medical student in internal medicine, the high-level teaching rounds supplemented comprehensive, hands-on learning opportunities about patient care. Richard Sogg, MD ’56

Pediatrics as a senior med student. A little girl was dying of pulmonary edema; she said she felt like she was drowning. I will never forget her terror. Thanks to all who shared recollections of your most memorable clinical rotation. We are pleased to announce we will now run Rounds online and in the print magazine. We invite your responses to the question for the December 2021 Rounds online: When you were a student at HMS, what were your favorite places to study, and why? And we look forward to your reflections on the question for the Spring 2022 Rounds physical issue: How have the public conversations on systemic racism and implicit bias affected how you interact with patients and colleagues? If you’d prefer we use only your class year with your response to the Spring 2022 question, please indicate that in your response. Responses can be submitted online: hms.harvard.edu/rounds; via email: hmsalum@hms.harvard.edu; by phone: 617-384-8520; or by mail: Rounds, Alumni Affairs and Development, Harvard Medical School, 401 Park Drive, Suite 505, Boston, MA 02215.

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ALUMNI

I OBITUARIES

Obituaries 1940s

Gilbert R. Cherrick, MD May 13, 2021

Russell L. Jeffery, MD May 1, 2021

1955

Richard E. Lindseth, MD May 4, 2021

1945

John M. Carey, MD May 19, 2021

Carl N. Brownsberger, MD June 9, 2021

1948

Sigurd B. Gundersen Jr., MD January 27, 2021

Lester Grinspoon, MD June 25, 2020

1950s 1950

Donald S. Gair, MD July 8, 2021 1951

John J. Garrett Jr., MD March 5, 2021 Robert C. Reid, MD July 27, 2021 Alfred L. Skinner, MD April 23, 2021

William G. Bush, MD July 3, 2021 Norman Barry Marshall, PhD April 19, 2021 1957

Jeremiah E. Silbert, MD May 24, 2021 1958

Carl David Brandt, PhD June 17, 2020 Stephen J. Healey III, MD April 26, 2021

1953

Albert C. Parker Jr., MD July 11, 2021

Tomiko I. Goldman, MD July 27, 2021

Charles Solow, MD June 6, 2021

P. Herbert Leiderman, MD April 1, 2021

Kirby L. Von Kessler, MD March 12, 2021

Donald B. Louria, MD July 26, 2021

1959

Leonard J. Triedman, MD March 19, 2021 1954

2000s

David K. Brewer, MD October 3, 2020

2005

1977

Eric B. Jelin, MD May 13, 2021

Paul S. Swerdlow, MD April 11, 2021

Larissa J. Lee, MD June 1, 2021

1961 2007

1956

Robert J. Zullo, MD August 6, 2021

Gordon F. Schwartz, MD August 16, 2021

1972

Josef E. Fischer, MD June 14, 2021 Kent H. Johnston, MD April 18, 2021 1962

Joseph W. Inselburg, MD February 29, 2020 1963

1990s 1990

Michael Evan Hughes, PhD May 4, 2021

Andrew B. Freese, MD June 30, 2021

2010s

1994

2017

Elizabeth M. Van Cott, MD April 13, 2021

Sam Bharat Dubal, MD October 2020

Charles E. Riordan, MD July 17, 2021 1964

Horatio Ransome Aldredge, MD April 1, 2021 1965

Wayne P. London, PhD May 5, 2021

This listing of deceased alumni includes those whose notices of death were received between April 1, 2021, and September 1, 2021.

1966

Joan L. Ullyot, MD June 19, 2021 1968

John A. Hobson, MD July 7, 2021

Samuel H. Wilson, MD April 23, 2021

Herbert Lessow, MD July 2, 2021

1970s Jare L Barkley, MD May 21, 2021 William B. Carey, MD July 25, 2020

1960s

1971

1960

Ormond L. Haynes Jr., MD October 22, 2017

Verne S. Caviness Jr., MD July 6, 2021

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dication 022 Dised in ce, and rvice as s mission. mination.

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ALUMNI

I NEWS

PRESIDENT’S REPORT

Preparing to Continue Our Good Work

Michael Rosenblatt, MD ’73, is senior partner at Flagship Pioneering in Cambridge, Massachusetts. 56

Nominate a Deserving Alumna or Alumnus Are you inspired by a peer who deserves recognition for showing dedication to the School? The Alumni Council is seeking nominations for the 2022 Distinguished Service Award for HMS Alumni. This award was established in 2019 to recognize MD alumni who have demonstrated loyalty, service, and commitment to HMS through volunteering, community building, service as an ambassador for the School, or otherwise supporting HMS and its mission. Submit your nomination by December 31 at alumni.hms.harvard.edu/nomination.

Alumni Council Welcomes Four New Members MD graduates selected four new Alumni Council members during the 2021 election. Three of those members will represent the second (classes of 2011–2015), fifth (1996–2000), and ninth (1976–1980) pentads, respectively: Jessica Ann Hohman, MD ’13 (Class of 2012); Sitaram (Ram) M. Emani, MD ’97; and Nancy Q. Petersmeyer, MD ’80. John F. Cramer III, MD ’74, will represent all classes as councilor-at-large. Learn more about the new representatives at alumni.hms.harvard.edu/election.

Thank You, Alumni Donors Philanthropic support from alumni is one of HMS’ proudest traditions. Gifts received during fiscal year 2021, which ran from July 1, 2020, to June 30, 2021, are helping to sustain the School’s mission to alleviate suffering and improve health and well-being for all by assisting students, bolstering research programs, and providing critical funding for emerging needs. MD alumni can view each class’s honor roll of donors at alumni.hms.harvard.edu/honor-roll.

Join Your Reunion Committee Classes ending in 2 and 7 will gather to celebrate June 2–4, 2022. Join your Reunion Committee to help plan a classspecific event and encourage your classmates to participate in the activities. Contact the alumni engagement team at 617-384-8520 or hmsalum@hms.harvard.edu for more information. Although we plan to celebrate in person, we will continue to monitor the coronavirus pandemic and post updates at alumni.hms.harvard.edu/reunion.

Provide Career Advice to Students Alumni are invited to sign up for the MD Alumni Advisor Program, which lets students select a volunteer who can help them choose a specialty, find the right residency, and practice interviewing for internships. Interested alumni can contact Dea Angiolillo, MD ’79, at dea.angiolillo@gmail.com.

RANDY GLASS

GRATITUDE AND ADMIRATION are the words that occupy my thoughts as my two-year term as Alumni Council president ends. Although a small group, the councilors very well represent the talent, values, and dedication of HMS alumni. I’m grateful to each member, but I especially want to thank departing members Mimi Choi, MD ’09, Allison McDonough, MD ’97, Ted Kohler, MD ’76, Al Sommer, MD ’67, and student representatives Shivangi Goel and Derek Soled. I found the two-year term for Council president, a relatively new institution, to be very useful for it allowed me to choose an ambitious long-term project: making HMS debt-free for students with financial need. This goal will not be met overnight. Nevertheless, the Council was able to form and launch the initiative. Now, two donor streams will drive us toward that goal. One stream involves Harvard University leadership, which has made this goal a University priority—a key step toward identifying someone who will make a transformative gift of approximately $300 million, which could be developed through an endowment mechanism. Another involves the REACH program and the alumni donations that help reduce the need for student loans. Alumni gifts under $1,000 already constitute support for an average of eight financial aid packages annually. The REACH program helps the School achieve its diversity goals and fits well with the agenda being developed by my successor, Kenneth Bridges, MD ’76. In addition, benchmarks for the debt-free initiative are being developed by Dean George Q. Daley, MD ’91, and the School’s development group. Meeting with HMS leadership is critically important to the Alumni Council’s success, so we welcome the fact that Dean Daley attends every Council meeting and updates members on HMS, the University, and the world of science and medicine. Our discussions are candid and highly interactive. At our meeting in May, Dean Daley told the Council about progress on HMS’ anti-racism initiative and about HMS alumni and faculty who have joined the Biden administration. I hope that this special relationship between the dean and alumni will remain strong. The updates from leadership throughout this past year showed Council members that, despite the tragedies it brought, the pandemic also led to several stunning successes for medicine, medical research, and medical education. We witnessed the profound impact of collaborations. We learned how HMS acted locally and globally to improve the health of patients by contributing to our understanding of COVID-19, developing vaccines, and convening collaborations across research disciplines. We admired the agility of our medical students as they surmounted the pandemic’s obstacles. And we experienced the bewildering human behavior regarding masks and vaccines, behavior that undermines efforts to save lives and defend against disease. Next time, will we be prepared, and will science rescue us so quickly? The humbling experience of the pandemic also sounded cautionary notes. We should not be too self-congratulatory. HMS, great as it is, doesn’t have a birthright to its top-ranked position. It needs to earn it continually, and it needs to be mindful of and learn from the competition. This is an arena where alumni, based throughout the medical world, can help. It’s a special moment in history and an extraordinary time to be a physician. I am so pleased to pass the gavel to Ken Bridges, a clinical researcher who translates science into new therapies. I thank the alumni for having given me the opportunity and honor to serve.

Alumni Announcements

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WILLS & TRUSTS

PLANNING

WHAT WILL BE YOUR LEGACY? Consider investing in longer, healthier lives Naming Harvard Medical School as a beneficiary of your will

TIP:

or trust is one of the simplest ways to leave a legacy to help secure a healthier tomorrow. If you’ve experienced a major life event, or if you’re creating your first estate plan, take the opportunity to consider designating a charitable bequest to HMS in

Update your will every 3-5 years or after major life events.

support of the area most important to you.You can give cash or a specific asset such as real estate or personal property. Bequest gifts of any size have a powerful impact on the School.

Have you recently: • Changed your marital status • Welcomed a new child/grandchild

Benefits

• Experienced the death of a loved one • Moved to another state • Bought or sold property

• Fulfill your financial, tax, and estate planning goals • Reduce or eliminate estate tax • Improve health and well-being for all

Learn more at hms.harvard.edu/bequests

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Nonprofit Organization 25 Shattuck Street Boston, Massachusetts 02115

U.S. Postage PAID Burlington, VT 05401 Permit No. 391

Electronic Service Requested

Dents in the golden years? The percentage of older adults in the U.S. population, now at around 16 percent, is expected to increase to 20 percent in less than a decade. Many worry that the paradigm for delivering care, especially long-term care, to members of this population does little to provide them empathy or ensure their dignity.

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