winterfall 2012 2012 Hopkins medicine

Comfort Zones Living better in the shadow of serious illness

Sometimes, the most intriguing career path is off the beaten one.

You may have read in this magazine that Johns Hopkins Medicine is becoming ever more global. Over the last decade, we’ve been engaged in dynamic collaborations with government, health care and educational institutions overseas designed to de- velop innovative platforms for improving health care delivery around the world.

To achieve this ambitious mission, we rely on physicians and other health care profes- To apply or to sionals who work onsite in leadership roles at these locations. This is an opportunity learn more, visit to push the boundaries of medicine in a broad-reaching, sustainable way—while hopkinsmedicine.org/ expanding your clinical exposure to complex cases and developing new research and careers and refer to the education projects in close collaboration with Johns Hopkins faculty and interna- requisition number tional colleagues. Questions? Current opportunities on the Johns Hopkins Medicine International [email protected] expatriate team: n Chief Executive Officer (Panama): 38143 n Chief Medical Officer (United Arab Emirates): 38147 n Medicine Practice Leader/CMO (Kuwait): 38541 n Paramedical Practice Leader (Kuwait): 38802 n Physician (Kuwait): 38652 n Project Manager/COO (Kuwait): 38501 n Public Health Professional—MD or MD/PhD (Kuwait): 38591 n Radiology Practice Leader (Kuwait): 38775 n Senior Project Manager/CEO (Kuwait): 38500

EOE/AA, M/F/D/V – The and Health System is an equal opportunity/affirmative action employer committed to recruiting, supporting, and fostering a diverse community of outstanding faculty, staff, and students. All applicants who share this goal are encouraged to apply. FEATURES 14 Defying Death Cells on a seemingly one-way road to dying have come back from the brink—raising tantalizing treatment possibilities. By Christen Brownlee Fall 18 Comfort Zones advocates are taking hospice strategies and pushing them “upstream.” By Jim Duffy 2012 24 The Last Word? Paul McHugh and colleagues are on a crusade to radically rethink the manual that has come Volume 35 * no.3 to define . By Mat Edelson

30 The Bea Project In his quest to find answers to his daughter’s genetic condition, Hugh Rienhoff ’82 has gone “rogue.” By Sharon Tregaskis

“I’m definitely outside DEPARTMENTS the establishment … 2 Letters I’m a gypsy and I Chestnuts about Chesney, and more. prefer that—there’s 4 Circling the Dome so much more freedom The new dean settles in and gets to work, mobile apps that address health needs around to work with different the world, organ donation goes viral, and more. kinds of people in 8 medical Rounds industry, academia, in Seeing is believing, overcoming ageism in kidney transplants, covered stents for mesenteric different companies.” ischemia, from twanging to talking. Hugh Rienhoff ’82, who launched “The Bea Project” to find answers to 12 hopkins Reader the genetic condition afflicting his Surgeon Marty Makary makes the case for young daughter (below). accountability to improve patient safety. Plus: p. 30 Remembering Victor McKusick, and the hope of . 45 annals of Hopkins E. Hunter Wilson ’53 formed bonds to Hopkins Hospital as a medical student that remained unbroken throughout his long career. By Neil A.Grauer

CLASS NOTES 36 News from and about graduates. OPINIONS 47 Curve After a decade of reflection, it’s time to move on. By Daniel Munoz ’04 48 Post-Op Toward honoring the traditions that have flourished here—and helping them expand. By Dean/CEO Paul B. Rothman

Cover illustration by James Steinberg Hopkins MedicinePhotogra p•h Fall by LE 2012AH F A•STEN 1 | Letters |

from the Chesney Chestnuts editor As an applicant for the Class of 1955, I was interviewed BEYOND THE CURE by Dean Chesney. I’d been Johns Hopkins is widely known as a forewarned that if the Dean place where medi- raised his hand to his ear, cal miracles seem to happen every that signified that he’d heard day—a place where enough and was turning off the best minds his hearing aid! But no one told me what that labor (often suc- cessfully) to find treatments and cures meant. for all kinds of difficult illnesses. In Sure enough, as I waxed eloquent about how the words of one administrator here, “Our docs can always pull some rab- I had been inspired to pursue medicine after bit out of a hat.” reading in Microbe Hunters about Metchnikoff ’s And, in fact, we proudly share accounts of these medical magic acts theory that lactobacillus protected the gut in every issue of this magazine. against pathogens, Dr. Chesney arose and With this issue, however, we depart from this curative focus to strolled over to the window, where he raised look at specialists who are delivering his hand to his ear. Taking this as an ominous Hopkins-level excellence along a parallel path. Known as palliative sign, I concluded my remarks and withdrew, care, it’s aimed at treating the and was doubly relieved when I was later in- symptoms of serious illness rather than the disease itself, and it is rapidly formed that I’d been admitted. gaining a foothold here, as you’ll discover in Jim Duffy’s cover story, Dr. Mountcastle states that Dr. Chesney’s one “Comfort Zones.” major fault was not accepting federal funding The timing couldn’t be better, nor the conditions within the field [Annals, Spring/Summer 2012], but then de- of health care more propitious. scribes him as being highly opinionated and Palliative care exists in harmony with medicine’s growing emphasis never laughing. This amused me because Dr. on “patient-centered” care, by Chesney struck me, at least in his later years, offering an individualized approach that relieves and suffering and as a reassuring father figure—in contrast to the creates the best possible quality of then young Dr. Mountcastle who was, at least life for patients at any stage of illness. It also saves money, by avoiding for us med students, a brilliant but humorless expensive hospital admissions (and and decidedly fearsome presence! readmissions) and instead keeping patients at home, with their families, It even seems likely that Dr. Chesney was where they can make the most of quite aware of the story about turning off his their time together. Within a medical environment hearing aid during interviews, and just did it like Johns Hopkins, which exalts to satisfy his young interviewees … and maybe the curative power of medicine, the effective delivery of palliative display his quiet wit! care represents a different kind of “success” story: one that is worth sharing, and celebrating. Nicholas Cunningham, MD '55, Dr PH ’77

2 • Hopkins Medicine • Fall 2012 | Letters |

CONTRIBUTORS

Editor Sue De Pasquale A graduate of the Rhode Island School of Design, illustrator James Class Notes Neil A. Grauer Steinberg (cover image) has done work for book and CD covers, Consulting Editor Edith Nichols and for a wide variety of newspapers and magazines, including Time, The Contributing Writers Christen Brown- New York Times, Forbes, Fortune, , and Reader’s Di- lee, Marjorie Centofanti, Lauren Glenn, gest. In 2001, he designed a postage stamp for diabetes research. Stein- Ellen Beth Levitt, Justin Kovalsky, Linell Smith, berg is based in Amherst, Mass. Shannon Swiger Art Director Max Boam Illustrator Nigel Buchanan (“The Last Word,” p. 24) works out of DESIGN David Dilworth, Abby Ferretti Photography Mike Ciesielski, Leah Fasten, a large warehouse in Sydney, Australia, with a bunch of other artists. A Monica Lopossay, Chris Myers, Keith Weller lecturer in illustration and design at Australian colleges, Buchanan’s cli- ents include Money Week Paris, The New York Times, MTV, and The Radio Administration Times in London. He is the recipient of a silver medal from the New Paul B. Rothman, Dean/CEO, Johns Hopkins Medicine York-based Society of Illustrators. Ronald R. Peterson, President, The Johns Hopkins Hospital/Health System Sharon Tregaskis (“The Bea Project,” p. 30) is a freelance writer Dalal Haldeman, PhD, MBA, Vice and farmer who lives in New York's Finger Lakes. She's reported on the President, Marketing and Communications politics of federal funding for stem cell research, the role of folic acid in Advisory Board fetal development, and the ethics of disclosure among genomic investi- Steve Desiderio, MD ’78, PhD ’81 gators and the people who participate in their studies. Her most recent Director, Institute for Basic story for this magazine examined the role of race in quality of care in Biomedical Sciences the emergency department. George Dover, MD, Director, Johns Hopkins Children’s Center David Hellmann, MD ’77 Vice Dean, Johns Hopkins Bayview Argye Hillis-Trupe, MD ’95 Professor, David Nichols, MD, Vice Dean for Education A New Hospital—And a New History Richard Ross, MD, Dean Emeritus, The Johns Hopkins School of Medicine Thomas Traill, MD, Professor, Medicine Cornelia Trimble, MD, Associate Professor, Leading the Way: A History Gyn/Ob Hopkins Medicine is made possible through the generosity of The Johns Hopkins Medical and Surgical Association, the organization of Johns Hopkins Medicine for every MD or PhD whose training or employment includes Hopkins. William Crawley, MD ’79, President With the opening of a new Johns Hopkins Hospital comes a new history of Johns Hopkins Medicine—the first in Printed in the U.S.A. more than 20 years. ©2012 The Johns Hopkins University and Leading the Way: A History of Johns Hopkins Medicine The Johns Hopkins Health System Corporation offers a lively, lavishly illustrated account of the exceptional

achievements of Hopkins physicians, researchers, teach- Hopkins Medicine is published in the fall, ers, and students since 1889, especially the extraordinary, winter and spring by Johns Hopkins Medicine, previously unchronicled expansion and accomplishments 901 South Bond Street, Suite 550, , MD 21231. of Hopkins Medicine over the past two decades. Written by Neil A. Grauer and featuring more than Send letters to Sue De Pasquale, Editor, at the above address. 400 photographs, many of them in color, Leading the Way e-mail: [email protected] provides all those interested in the story of Johns Hopkins Letters may be edited for clarity and length. Medicine—or even just in the advances in medicine itself over the past 20 Web address: www.hopkinsmedicinemagazine.org years—with the riveting story of how Hopkins remains in the forefront of medical education, research, and patient care. Phone: 443-791-1526 Persons not on the magazine’s mailing list $60.00 may order a three-year subscription by send- ing a check for $40 (made out to Hopkins Available through The Johns Hopkins University Press: www.http://JHUPBOOKS. Medicine magazine) to the editor. press.jhu.edu ; 410-516-6956 or 1-800-537-5487

Hopkins Medicine • Fall 2012 • 3 CIRCLING the dome First Impressions The new Dean/CEO settles in and gets to work.

Paul B. Rothman officially began work as Dean/CEO of Hopkins Medicine on July 1, but he’d already become a familiar presence, having made weekly visits to campus since the announcement of his appointment last December. We checked in with him over the summer to get his initial about Hopkins and its people. Look for more extensive coverage of the new Dean/CEO in future issues of Hopkins Medicine Magazine. Interview by Justin Kovalsky

Your first week on the job coincided with the aftermath What is your strategy for moving forward with of a summer “derecho” that left parts of Baltimore with- any change here? out power for a week… Before I do anything, I really want to understand So I walked into a blackout. My wife was laughing because Hopkins’ culture. I think I understand the value sys- when I took the dean job at the University of Iowa, the day I tem, but I want to know it well. I’ve started to gain was approved by the board there was a huge flood in Iowa City, knowledge of the people and the institution, but over and I actually had to close the medical school for a week. That the next couple of months I want to solidify that and was my first act as dean. So I guess I’m used to coming in under get a much better understanding of the place. adverse conditions. What do you see as your greatest challenges? What most excites you about your new role? We’re in a time of change in health care. The country The opportunity to work with the outstanding people at Hop- needs institutions to step up and develop systems of kins. People here are committed to developing new systems of care, and that’s a big challenge, especially for academic care that are cost-efficient and of the highest quality, with a institutions. But I think we’re up for the challenge. focus on the patient and on patient safety. I’m also excited by Hopkins has to lead in developing a cost-effective the amazing quality of education and research here. Many places system that continues to deliver high-quality and safe have seen drops in funding over the last several years but Hop- care. kins continues to grow in research. The restraint of federal spending, both in terms of health care and research, is going to be a challenge. How will your background in basic science color your ap- I’m really worried about flat NIH budgets. I know proach to Hopkins’ research enterprise? that the nation is committed to medical research and I know the life of scientists, and I’ve been a great advocate of helping to find treatments for disease. I understand basic science. I understand how important basic science is to that there are financial constraints to that, but I moving all discovery forward and that it’s the basis for finding think it would be shortsighted to really cut NIH. treatments for disease.

GETTING PERSONAL Paul B. Rothman Areas of specialty: Hometown: New York City First jobs: Stock clerk in a paint store; summer camp Professional: Dean of the Rheumatology and molecular Favorite music: Jack Johnson; counselor Carver College of Medicine, immunology; research focus on a bluegrass group called Nickel University of Iowa, 2008-2012 the role of cytokines in leukemia Creek; old classic rock Favorite (non-medical) and in immune response to authors: Richard Russo, Favorite food: Chinese asthma and allergies Ethan Canin, Michael Chabon

4 • Hopkins Medicine • Fall 2012 Meeting a Burning Need Mobile apps address health needs worldwide.

In January 2009, on the outskirts of Nairobi, an over- turned tanker gushed thousands of gallons of gasoline, attracting a crowd that attempted to collect the spilt fuel. Nearly 100 died in the explosion that ensued, and almost twice as many sustained burn injuries, inundating local hospitals that were ill-equipped for the catastrophe. As part of a Johns Hopkins Burn Center team deployed to help, director Stephen Milner witnessed firsthand the devastation—inspiring him to seek an effective way to teach others how to properly care for burn victims. The result? A mobile application that is now available online for medical students and physicians. The Burn Center product is among a fast-growing number of mobile apps being developed throughout Johns Hopkins to provide health and medical informa- tion to physicians, medical students, emergency medicine personnel, and global health workers. Born out of a collabora- While your long-term plan is still percolating, tion with Harry Goldberg, Visit the iTunes store what’s on the shortlist? assistant dean and director or Google play for The shortlist is to develop a strategic plan. We have to of academic computing for the following apps: think about where the institution is going to go in the the School of Medicine, the • Johns Hopkins Antibiotic next three to five years, so that’s my primary goal right Burn Medical Education Guide now. And that’s a process that involves many people and app, or BurnMed, utilizes • Johns Hopkins Atlas of a lot of input, and a system to make sure that we have a combination of pictures, Pancreas Pathology video, and text to illustrate people on board to get where we want to go. • Johns Hopkins BurnMed how to handle victims in (Pro and lite versions) the eight hours following a What do you see as the role of collaboration? • Johns Hopkins Diabetes burn—a period critical for Guide Selflessness obviously is the heart of collaboration. I think survival. For example, by • Johns Hopkins eMOCHA scientists love to collaborate—it’s inherent to them. Some- highlighting burned areas on • Johns Hopkins eMOCHA times we put up administrative barriers that inhibit the a rotatable 3-D figure of a TB DETECT natural flow of science. The people who are successful man, woman, or child using • Johns Hopkins HIV Guide are the people who are oblivious to those barriers and go an iPad or iPhone, the user • Johns Hopkins HIV ahead and make sure science gets done. My job is to facili- can quickly calculate how Dementia Scale tate that and make sure that there aren’t any barriers for much fluid to administer. • Johns Hopkins Tech the flow of science. “This app is designed so Transfer App the user can understand For clinical activity, collaboration is also key. Again, the underlying procedures there are systems of reimbursement and administration used to treat a burn victim within a few minutes,” says that sometimes don’t allow the natural flow of care across Goldberg. “In a textbook, one could read several chapters disciplines to take place in a patient-centered way. Our and they still may not understand these procedures due goal now is to overcome anything that would inhibit a to the limits of text.” collaborative approach to our patients and refocus on Milner says apps are fast, accurate, and accessible in patient-centered care. comparison to traditional treatment methods that involve complex mathematical equations. Two-dimensional textbook charts don’t show the surface area of the sides of the body, top of the head, and bottom of the feet—a shortcoming, he says, that could lead to dangerous miscal- culations, as too little or too much fluid can be lethal. Family: Wife, Frances Jane Meyer, a Pets: “Arwen,” a rescue dog Milner and Goldberg are just two of many across Hop- clinical gastroenterologist, and three that is part black Lab, part kins who’re developing applications designed to impart children: Alissa, a sophomore at Australian sheep dog. “Libby,” medical knowledge.“This is another way to share the Johns Amherst College; Daniel, a freshman the first cloned ferret in the Hopkins values, mission, and brand with places we have at Brown; and Eric, a ninth-grader at world (“She’s published”) not yet reached internationally,” says Montserrat Capdev- Friends School of Baltimore ila, of the university’s Tech Transfer Office.Shannon Swiger

PHOTO BY Will Kirk Hopkins Medicine • Fall 2012 • 5 | Alpha Docs | Phenom Social networking proves a boon to boosting organ donation.

In medicine, viruses usually are a bad thing. When a new, potentially lifesaving idea goes viral on the Internet, however, that’s something else. Just ask Andrew Cameron ’98, surgical director of Hopkins’ liver transplant program, and Sheryl Sandberg, a

former undergraduate classmate of Cameron’s at Harvard, Pho t o b y MI KE C I ES ELSK who now is chief operating officer of Facebook. Surgeon Andrew Cameron (pictured above) teamed up with Face- When Cameron and Sandberg attended their 20th Har- book's Sheryl Sandberg to go viral with organ donation. vard reunion in 2011, they got to talking. Five years before, Sandberg had read an alumni magazine profile of Cameron says Cameron. “Maryland had an average of 10 donors per day in which he described the anguish that transplant surgeons feel prior to the Facebook initiative,” he says. “In the first week after it when they can’t do anything to help patients who die because of was launched, Maryland had 781 new donors sign up,” reflecting the the chronic, critical shortage of donated organs in the U.S. nationwide trend. A month later, the donor registration rates still At the time Sandberg read that article in 2006, Facebook was were elevated, he adds. only two years old—but by 2011 it had become an Internet social This is a welcome development for the more than 114,000 networking behemoth with millions of subscribers. As Cameron people requiring new livers, hearts, kidneys, and other organs and she talked—and brainstormed—at their college reunion, they throughout the U.S. One of those individuals dies every four hours reached a joint epiphany. “Doctors save lives one person at a time,” while waiting for a transplant. Although the need for organ donation recalls Cameron, an associate professor of surgery. “Sheryl is able continues to increase, the rate of donation over the past 20 years to reach people millions at a time. We have a public health problem has been almost flat, despite widespread public campaigns. that really just needs education, communication, and discussion.” The Hopkins liver transplant program that Cameron heads is Now Facebook is providing it. Since May 1, Facebook users have one of the most forward-looking, evidence-based ones in the na- been able to share their organ donor status with friends, family— tion. This year, he and his surgical colleagues will perform approxi- and the world—as they do other basic information. The informa- mately 50 liver transplants. “Getting people to donate their organs tion is part of the site’s new Timeline feature, which asks users to has been an intractable public health problem,” Cameron says. “It share stories and photographs. stands in contrast to other public health campaigns such as seat Facebook also is making it easier for its members to obtain belts or drunk driving, which have major impacts. If we succeed on information about organ donation—simultaneously dispelling myths Facebook with organ donation, it could be a model for how to use and misperceptions—and is providing links to state databases of-the-moment social media to solve important medical issues.” where users can make their desire to donate their organs official, Among these is the need for healthy individuals to donate a just as they can do when getting their driver’s license. piece of their liver, rather than designate their liver for use after Since the launch, the results of the Facebook organ donation their death. Cameron says his program is “interested in using social initiative have been phenomenal, boosting the nationwide increase media in novel ways” to facilitate living donor transplants, too. in registered donors by a staggering 1,183 percent in its first week, Neil A. Grauer

Robert Adams, associate professor of American Federation for Medical Research, Hugh Calkins, professor of medicine, molecular and comparative pathobiology, has the Association for Clinical Research cardiology, and pediatrics and director of been appointed associate provost for animal Training, the Association for Patient the arrhythmia service, research and resources. Adams, a 35-year Oriented Research, and the Society for laboratory, tilt table diagnostic laboratory veteran of the faculty, has been filling the po- Clinical and Translational Science. and the ARVD (arrhythmogenic right sition on an interim basis, directing the care Frederick Brancati, professor of ventricular dysplasia) program, has been of more than 150,000 animals—mostly mice medicine and epidemiology and chief of the named president-elect of the international and rats—used by university researchers. Division of General Internal Medicine, has Heart Rhythm Society. Calkins also is the lead author of the 2012 Expert Consensus Lawrence Appel, professor of medi- been named Distinguished Service Professor Statement on Catheter and Surgical cine and director of the Welch Center of Medicine by the university’s board of Ablation of Atrial Fibrillation. for Prevention, Epidemiology and Clinical trustees. Such a designation is given to select, Research, has received the 2012 National senior faculty to recognize their exemplary Phillip Dennis has been named director Award for Career Achievement and service. Brancati is recognized worldwide as of the Sidney Kimmel Comprehensive Contributions to Clinical and Translational an expert on the epidemiology and preven- Cancer Center at Johns Hopkins Bayview Science. It was awarded jointly by the tion of type 2 diabetes and related conditions. and director of the Department of

6 • Hopkins Medicine • Fall 2012 | Alpha Docs |

Oncology. He plans to expand and inte- Award from the American Medical Women’s were William Kaelin Jr., a Hopkins grate oncology care across departments to Association. The award is bestowed on a intern and resident from 1987 to 1988 and provide better access to cancer screening, woman physician who has made exceptional now a professor at the Dana-Farber Cancer diagnosis, and treatment. He also will lead contributions to medical science, especially in Institute, and Peter Ratcliffe, of Oxford all lung cancer treatment efforts within women’s health. University, who discovered how oxygen the center’s Upper Aerodigestive Cancer Constantine Lyketsos, professor and regulates HIF-1. Program, including the creation of a Center director of the Department of Psychiatry Patrick Walsh, Distinguished Service of Excellence in Thoracic Oncology. at Hopkins Bayview, has received the Professor of Urology and former director Paul Englund, professor emeritus of 2012 American Association for Geriatric of the Brady Urological Institute, has been biological chemistry; Rachel Green, pro- Psychiatry’s Distinguished Scientist Award, the named the 2012 recipient of the American fessor of molecular biology and genetics; and highest national honor in . Academy of Arts and Sciences’ Francis Se-Jin Lee, professor of molecular biology Lyketsos is a lifetime member of the associa- Amory Prize. Awarded since 1940, the and genetics, have been inducted into the tion, which strives to enhance the knowledge Amory Prize recognizes major advances in National Academy of Sciences, one of the and practice standards in geriatric psychiatry. reproductive biology and medical care. United States’ top scientific honors. Gregg Semenza, professor of pediatrics, Pamela Zeitlin, professor of pediatrics, Sewon Kang, professor and director of medicine, oncology, and radiation oncology, director of pulmonary medicine, and co- the Department of Dermatology, has been is among three recipients of the Institute director of the Cystic Fibrosis Center, has elected president of the Photomedicine of France’s Lefoulon-Delalande Foundation received the American Thoracic Society’s Society, an international organization of phy- Scientific Grand Prize for 2012. The award 2012 Elizabeth A. Rich, M.D. Award. The sicians, molecular biologists, physicists, and recognizes Semenza’s work at Hopkins in honor recognizes outstanding women and engineers based in the United States. purifying and isolating the protein HIF-1 leaders who have made significant contribu- (hypoxia-inducible factor-1), which switches Pamela Lipsett, professor of surgery, tions to the thoracic society in pulmonary, genes on and off in cells in response to low has been given the 2012 Woman in Science critical care, or medicine. oxygen levels. Co-recipients of the award

Parsimony’s Pay-off Two faculty have grown a nest egg to support postdoc training.

N. Franklin Adkinson, Jr. ’69 and his longtime colleague “In the initial years, the Robert Hamilton, PhD ’80, of Hopkins’ Dermatology, interest from the fund is not Allergy and Clinical Immunology Reference Laboratory, don’t going to be that much, so it’s consider themselves major league philanthropists. going to cover special expens- Instead, they’ve just been very careful with the money that es associated with our fellows their lab—better known by its initials, DACI—has earned over program,” such as medical the past three decades. They and their faculty colleagues, tech- insurance for the fellows and nicians, and fellows perform highly specialized allergy testing on board examination fees, Ham- blood samples they receive from clients throughout the U.S. ilton says. “Eventually, we may and around the globe, all seeking assistance in the diagnosis have enough interest from and management of human allergic disease. Other income has the fund to actually provide come from special contracts with pharmaceutical companies a fellowship, so that we pay a that want to test the immunogenicity safety of new drugs. stipend to the fellow. But this DACI’s leaders also have been scrupulously frugal about will take time.” how they run their operation. “I’ve tried to be diligent in bare Although Adkinson notes bones expenses over many years,” says Hamilton, the lab’s that it was surpluses gener- Scrupulously frugal: Hamilton (left) director, explaining that he often saves money by doing basic ated by Hamilton’s efforts that and Adkinson. research-related chores himself rather than hiring a new created the endowment fund, technician to handle them. Such parsimony and productivity Hamilton insisted that it also bear Adkinson’s name. produced a sizable nest egg, as Hamilton spent 30 years squir- “Dr. Adkinson and I have worked together for more than 30-odd reling away any surplus funds “so we could use them for some years,” says Hamilton. “I’ve always appreciated his sage guidance, and positive purpose for this division,” he says. therefore I feel he should be No. 1 on the listing. And because he’s been This past spring, they did just that. With $600,000 in the director of the allergy and asthma group training program here at painstakingly saved surpluses, they established the Adkinson- Hopkins for so many years, he deserves that position.” Hamilton Educational Endowment in the Division of Allergy It is hoped that the Adkinson-Hamilton Endowment will become a and Clinical Immunology. Interest from the fund—believed to focal point for future divisional fundraising in support of postdoctoral fel- be the first ever created by two faculty members with a labo- lows. While it’s too early to tell if it will, Adkinson says alumni response to ratory surplus—will support postdoctoral training programs. the endowment’s creation so far has been “laudatory.” NAG

Photo by MIKE CIESIELSKI Hopkins Medicine • Fall 2012 • 7 medical ROUNDS Seeing is Believing New procedure offers global view of the liver, reducing sampling error.

A few years back, after a checkup flagged elevated liver enzymes, forty-something Max Zacur* learned that he had hepatitis C, genotype 1. A local gastroenterologist performed a percutaneous liver biopsy—the older sort with palpation first and “blind” needle insertion. But since the resulting pathology report showed little inflammation and no fibrosis, the hallmarks of active disease, Zacur opted to bypass treatment, given its reputation for side effects and low efficacy. Last year came a repeat: His liver enzymes were again suspect, though he still felt fine. This time, Zacur went to a radiologist for a biopsy, one guided by ultrasound. And this time, the sample yielded quite different results, showing severe, significant fibrosis. “Fortunately, therapy for hepatitis C is now more potent,” says Hopkins hepatologist Zhiping Li. “The downside, however, is that side effects have worsened. People daily feel like they have the flu. Some develop anemia.” Zacur’s apparently burgeoning hepatitis Zhiping Li describes mini-peritoneoscopy as a “true advance” over traditional gave Li pause, and he realized that an accurate laparoscopy. In hepatitis patients, he’s been able to reduce liver sampling global survey of Zacur’s liver disease was in error, a traditional hazard since liver disease rarely spreads uniformly. order. For the patient’s third biopsy—this time at Hopkins—direct visual inspection of the liver via peritoneoscopy would guide the needle. Three advantages stand out, he says. “One is that you Brought to Hopkins from Germany three years ago, mini- can retrieve a larger tissue sample.” That’s in contrast to peritoneoscopy lets endoscopists visualize the peritoneum ultrasound where housing the biopsy needle within the and its contents via a small, streamlined instrument fed into probe limits needle size. Also, Li adds, “we use sedation, and a single port. A second opening admits the biopsy needle. patients are happier with that.” Last, he says, post-biopsy The technique is extremely nimble because both ports need bleeding isn’t a problem. “We catch bleeding right away be only a few millimeters wide and can be put anywhere in because we can see it. That avoids painful hematomas that the abdomen that a patient’s condition allows. are almost universal otherwise.” After biopsy, two Band-Aids are enough to close. The major benefit, though, lies in damping down liver- “It’s a true advance over traditional laparoscopy, which sampling error—a traditional hazard, Li says, because liver involves 5- to 10-millimeter suture-requiring holes in the disease rarely spreads uniformly throughout the organ. abdomen,” says Li. That certainly was the case with Zacur. Though his frontal The new mini-peritoneoscopy service is unique in the left lobe showed spots of fibrosis, his right was clean. Thanks United States, though the technique has spread throughout to the global view achieved through mini-peritoneoscopy, Europe. Li has seen some 50 patients so far, mostly with Li’s recommended a “watch and wait” approach, which hepatitis. Zacur was happy to follow. Marjorie Centofanti

8 • Hopkins Medicine • Fall 2012 * Patient’s name has been changed to protect privacy. | Medical Rounds | Overcoming Ageism in Kidney Transplants Considering older donors—and recipients—could boost quality of life for thousands.

In the world of kidney transplanta- predictor of outcomes than any other tion, younger has always been deemed criteria that we are able to measure,” better—at least in terms of selecting Segev says. recipients and donors. The logic was It’s not only older recipients who simple: Younger recipients would ap- are sometimes overlooked. Older pear to have better odds of survival potential donors, too, have often been and success, and younger donors would disregarded, even though they could offer organs that had seen less wear have excellent outcomes and continue and tear. to live a high-quality life. In one study, But in the Department of Surgery Segev and his colleagues examined here, researchers are finding that this more than 200 living donors, ages 70 assumption isn’t necessarily true. In fact, and up. They looked at two things: says transplant surgeon and researcher how well the recipients of their organs Dorry Segev, studies conducted did and how well the donors them- during the last decade have shown that selves did. They then compared those older patients could be just as eligible donors to healthy people of the same and hold just as much promise as their age who had not donated a kidney. younger counterparts. Yet every year, the possibility that kidney transplantation “We found that the surgical risk for tens of thousands of patients are turned could be an option for patients 65 and a properly screened older adult was no away from—or not even referred to— older. Second, those patients—recipients different than for a properly screened transplant programs because of their age. and donors alike—need to be identified. younger adult,” Segev says. “We also Instead, they’re left with only one choice: “The question is how do we decide found that older donors lived just as long years and years spent on dialysis, with no whether someone is robust enough to as their non-donor counterparts. end in sight. get through the transplant operation so That’s not to say that a 70-year-old is “That feels almost as bad as a death they can actually reap the benefits of it?” necessarily the best donor for a 20-year- sentence for many of these adults,” Segev Segev says. One of the most promising old recipient, particularly if other options says. “But for the right patients, older criteria is a condition that in recent years are available. Older donors, Segev ex- has become increasingly prominent in the Pho t o b y K e i h W elle r ones included, transplantation offers a plains, are ideal for older recipients who chance at survival and a much higher field of geriatrics: frailty, or physiologic would generally require a shorter organ quality of life. Right now, the referral rate reserve. In the past, frailty was limited to shelf life. Still, considering older donors for kidney transplantation in older adults a vague assessment by an experienced increases a patient’s pool of potential liv- is almost one-tenth that of younger clinician from the foot of the hospital ing donors, particularly for older patients adults. But we recently showed that bed; today it can actually be quantified whose support networks are often thousands of older adults every year go with a simple set of tests. populated by people their own age. on dialysis, despite being excellent candi- By measuring walking speed, grip “Patients on dialysis may have to wait dates predicted to do exceptionally well strength, fatigue, physical activity, and years and years before they get a donor and derive tremendous benefits from a muscle loss, physicians can often de- offer from a waiting list,” Segev says. “If kidney transplant. Yet they never make it termine whether an older patient is fit you can find a living donor, that’s a much to us.” for any procedure—transplantation better option, because you can spare The challenge today is twofold: First, included. “We recently published that a yourself many years of waiting and pos- the medical community needs to accept patient’s level of frailty was a stronger sibly dying on dialysis.” Lauren Glenn

“ We found that the surgical risk for a properly screened older adult was no different than for a properly screened younger adult. We also found that older donors lived just as long as their non-donor counterparts.” Dorry Segev, transplant surgeon

ILLUSTRATION BY STUART BRIERS Hopkins Medicine • Fall 2012 • 9 | Medical Rounds | Eating Again Covered stents may prevent need for bypass in fatty arteries that feed intestines.

ixty-two-year-old Homer Pullen, the arm may be an easier of West , had already route due to the sharp gone through a triple coronary angled take-off of the Sartery bypass surgery when he superior mesenteric and developed fatty deposits in the arteries celiac arteries. that feed his intestines, a condition Abularrage believes known has mesenteric ischemia. that covered stents may “I tried to eat but couldn’t because be more effective than of the pain, and I went from 180 older, bare metal stents pounds to 132,” says Pullen. “It was in keeping the arteries heartbreaking.” open because they have Although coronary atherosclerosis more radial force and is in the news all the time, there’s little can decrease the scarring attention paid to mesenteric ischemia, that thickens blood says vascular and endovascular surgeon vessels (known as intimal Christopher Abularrage. As a hyperplasia). result, by the time patients like Pullen “Uncovered stents have come for treatment, they are usually been used as a bridge to very weak and undernourished and bypass—treating patients’ are not good candidates for an open symptoms so that they operation to bypass the blockages. are pain-free and able to Got it covered: Christopher Abularrage. So Abularrage is taking a minimally eat more and build their invasive approach, using covered strength. However, covered stents fishing, and other activities with his stents. Patients are awake but sedated, may replace the need for a bypass,” friends that he couldn’t enjoy before. experience minimal pain, and can go says Abularrage. None of the patients Abularrage says that most patients home the next day. he treated more than a year ago with with chronic mesenteric ischemia are “We start by inserting a catheter covered stents has had a recurrence. over age 60, often with a history of through the patient’s arm, down the Such was the case with Homer smoking and a high cholesterol level. chest into the abdominal aorta,” he Pullen. A month after Abularrage It affects more men than women. says. “From there, we pass a wire performed the covered stent procedure, Patients present with abdominal pain through each blockage and then deploy starting through Pullen’s arm, the after eating and significant weight loss, a covered stent that is mounted on a West Virginia man had gained back 20 but sometimes the symptoms can be balloon to open the vessels.” While pounds. “I now eat everything—even mistaken for gallbladder disease or the procedure can also be performed spaghetti with meat sauce and ham and kidney stones, which is why it is often through the femoral artery in the groin, eggs, and I feel great,” says Pullen. He’s diagnosed after it has progressed. Abularrage explains, going through also been able to go back to hunting, Ellen Beth Levitt

Hearing loss has been linked with 2001 to 2004 cycles of the National Hearing Goeth a variety of medical, social, and Health and Nutrition Examination cognitive ills—including dementia. Survey, a research program that has Now, says Hopkins otologist Frank periodically gathered health data from Before a Fall Lin, new research shows that hearing thousands of Americans since 1971. loss may also be a risk factor for During those years, thousands of Loss of hearing could make it another huge public health problem: adults ages 40 to 69 had their hearing difficult to maintain balance falls. tested and answered questions about and gait. To investigate possible connections whether they had fallen over the past between hearing loss and falling, year. Lin joined up with Luigi Ferrucci Their study found that people with of the National Institute on Aging. a 25-decibel hearing loss, classified as Together, they used data from the mild, were nearly three times more

10 • Hopkins Medicine • Fall 2012 | Medical Rounds | From Twanging to Talking The humble jaw harp gives voice to those without larynxes.

Musician Wayne Hankin was listening to the radio one day in Califano invited Hankin to Hopkins to present his idea to December 2007 when he heard a segment featuring Hopkins head himself and Webster in person. After a couple of short les- and neck surgeon Joe Califano, who spoke about the post-sur- sons, both were speaking with the instrument—suggesting gery challenges facing patients with advanced laryngeal cancer. that it might be a viable option for patients, too. While a total laryngectomy offers a high cure rate, “the obvi- Within months, Webster and Hankin had started a small ous downside is no more sound source for patients’ voices,” says pilot study to teach jaw harp-generated speech to a dozen speech language pathologist Kim Webster, whose Hopkins total laryngectomy patients. The method is straightforward: caseload is filled with patients dealing with this issue. Users mouth words while strumming the jaw harp in their Most patients have one of two options for replacing their mouth. Although results were mixed—not every patient natural voice: either the hand-held, battery-operated electrolarynx, was a fast learner—the majority were able to pick up the or a tracheoesophageal prosthesis (also known as a TEP). A third technique quickly and with relative ease. method, used less commonly today, is esophageal speech, a tech- The low-cost jaw harp holds decided advantages over ex- nique in which patients learn to “burp” their words by swallowing isting technology, Webster says. With no special equipment air and forcing it out of the esophagus. or batteries necessary and a small learning curve, it could be Though these methods do offer patients ways to talk, each has a great option for patients in resource-poor settings. its drawbacks, Califano explains. Electrolarynxes and TEPs can cost Adds Hankin, “If you take care of your instrument and thousands of dollars over patients’ make an effort to learn it, the lifetimes for care and upkeep, and total charge for patients could esophageal speech can be extraordi- be just a few dollars over the Pho t o b y K e i h W elle r narily difficult to learn. None of these course of a lifetime.” options is a good fit for patients in Hankin and Webster pre- developing countries, where resources sented their work at the Ameri- such as equipment and batteries—and can Speech-Language and Hear- even education—are scarce. ing Association annual meeting Hankin, who plays the jaw harp in 2009 and at a Baltimore Adult professionally and uses it to generate Communications Disorders twangy, buzzy-sounding speech for Interest Group in 2011. They’re fun, wondered whether his instrument also preparing a manuscript on might offer an alternative for patients. their pilot trial for publication. So he called Califano. Says Hankin, “This adds an- Initially, the doctor was skeptical. “I other real option to the limited it sounded like a nutty idea,” set of tools that cancer patients Califano says. “But when Wayne start- can use to get their lives back.” ed talking on the phone with his jaw Christen Brownlee harp, I could see that it really works.”

likely to have a history of falling. Every environment, making tripping and hearing in the elderly—through additional 10 decibels of hearing loss falling more likely. Another is hearing aids and cochlear implants— increased the chances of falling by 1.4- that the might be overwhelmed might improve other problems fold. This finding still held true, even with demands on its limited resources. associated with hearing loss, including when researchers accounted for other “Gait and balance are things most falls. factors linked with falling, including people take for granted, but they are Finding ways to reduce falls might age, sex, race, cardiovascular disease, actually very cognitively demanding,” save millions in health care costs in and vestibular function. Lin says. “If hearing loss imposes a the United States each year, as well as Lin says that he and Ferrucci aren’t cognitive load, there may be fewer the health of thousands of people. “If sure why hearing loss and falling are cognitive resources to help with we can prevent even a small fraction of linked, but one possibility is that maintaining balance and gait.” falls by improving hearing,” Lin says, people who can’t hear well might not Lin and his colleagues are currently “that could make a huge impact on have good awareness of their overall investigating whether improving people’s lives.” CB

ILLUSTRATION by Martin O'Neill Hopkins Medicine • Fall 2012 • 11 | Hopkins Reader | It’s Time for Transparency Surgeon Marty Makary makes the case for accountability to improve patient safety.

Every physician has horror while making treatment options and Then there were the “styles” of stories about witnessing the inap- institutional policies more transpar- two surgeons (again, not at Hopkins). propriate, excessive, or incompetent ent. As part of this effort, he wants to One was warm and affable, the other treatment of a patient—and about how ensure that the public has easy access brusque and demeaning. The affable a professional code of silence ensures to every hospital’s outcomes data on physician charmed patients with that the public won’t learn about the various medical procedures. his bedside manner, but his surgical failings of the offending practitioners Appearing frequently on both technique was abysmal. His patients or institutions. CNN and the Fox network as a medi- suffered a disproportionate number Marty Makary, a surgical oncolo- cal expert, Makary knows the value of painful, costly complications—a gist and gastrointestinal surgeon at of riveting stories to make a point. He fact well known in the hospital. The Hopkins Hospital, seems to have more fills his book with them. residents called him “Dr. Hodad” (for of these tales to tell than most—or For example, during his training in “Hands Of Death And Destruction”). at least is more willing to do so. As another hospital, he saw a gastroen- The other surgeon was known as “The accountability is becoming a new terologist, unfamiliar with endoscopic Raptor.” He humiliated staff and byword in American medicine—par- removal of a colon polyp, display patients alike. His surgical technique, ticularly with the nation’s new health admirable humility by calling upon a however, was superb. The residents care act establishing “accountable care younger colleague to perform a quick despised him personally—but he was organizations”—the timing could not and safe polypectomy by using a the one they’d want to operate on be more propitious for Makary’s new wire snare passed through them or a family member. book, Unaccountable: What Hospitals the scope. Days later, The staff and residents knew that to Won’t Tell You and How Transpar- air their concerns could be professional ency Can Revolutionize Health Care suicide, so they remained mum about (Bloomsbury Press, 2012). the individuals and incidents for which Although the drive for account- they coined devastating nicknames. ability in health care is accelerating, Divided into three parts, “Some Makary contends that much remains Random Doctor,” “The Wild West,” to be fixed. Many information sources and “Transparency Time,” Makary’s on patient safety are hidden in an 17 chapters are a fascinating blend of impenetrable maze of websites, he discomforting facts, common sense notes. Medical institutions and practi- proposals, and an impressive call-to- tioners continue to mislead prospective action. patients with deceptive advertising, “To say that we provide amazing acting as salespersons for—or defen- technology and have the world’s best sively overusing—potentially unneces- research, therefore we are the saf- sary treatments. What’s more, hospitals est, is something that doctors say is fail to discipline errant physicians, and part of the problem in health care,” they don’t report fully on the outcomes says Makary, who is also an associ- of the care they provide. ate professor of health policy at the “This is my passion,” says Makary, Bloomberg School of Public Health. 41, who spent two years of nights and “We need to be open and honest about weekends writing Unaccountable. A col- our mistakes, our shortcomings, where league of Hopkins’ renowned patient a respected but clearly self-important we can do better, our poor-performing safety advocate ’91, colorectal surgeon spurned Makary’s areas in the hospital. And if we can’t Makary has been in the vanguard of suggestion that he seek the assistance be honest about our problems, then we such initiatives. He was instrumen- of the wire-snare expert on an identi- really can’t improve on them. tal in developing the World Health cal case. Instead, the surgeon insisted “By and large in America, when Organization’s wide-ranging medical on performing an invasive operation people walk into a hospital, they walk procedure safety checklist. He is also to remove the patient’s colon. His rea- in blind. And we can do better than a leader of the movement that aims to son? “I just like to take these out with that.” Neil A. Grauer improve the overall standard of care surgery.”

12 • Hopkins Medicine • Fall 2012 illustration by Sherrill Cooper | Hopkins Reader |

MORE BOOKS

Victor McKusick and Hopkins colleagues developed the History of Medical a liberating overview, or meta- Genetics, Krishna R. model, for its practice. It held Dronamraju, PhD, and Clair that certain common factors A. Francomano, MD, Editors could be found in the applica- (Springer, 2012) tion of all the methods, and that these common elements Krishna Dronamraju of treatment accounted for (Fellow, medical genet- psychotherapy’s success. ics, 1965) and Clair Frank wrote that a key Francomano ’80 (HS, to any effort to address the faculty, medical genetics, mental distress of patients 1980-94) have assembled who feel they have lost control an all-star lineup of medi- over their lives and is cal luminaries and family Medicine, writes, “It is greatly to strive toward restoring the members to pay tribute to to be hoped that in due patients’ morale and renew- Victor McKusick (1921-2008), ten by 1978 Nobel laureate course, a detailed and objec- ing their hope that they can, the genetic medicine giant Hamilton Smith ’56 (fac- tive scientific biography [of indeed, understand the source whose 65-year career at ulty, microbiology, 1967-1998). McKusick] will be written.” of their distress and master it. Hopkins—from 1946 School Other current or former Whoever writes it will find Rarely has a single book of Medicine graduate to faculty, house staff, or fellows this volume a valuable source. had such a profound impact ever-active, iconic figure who contributed appreciation Neil A. Grauer on a medical specialty. Revised until his death—was the or recollection pieces about in 1973 and 1991, Persuasion longest consecutive tenure their erstwhile mentor or and Healing remains in print, of any faculty member in the colleague include Aravinda The Psychotherapy of in many languages. Its three School of Medicine’s history. Chakravarti, Edison T. Hope: The Legacy of editions have been “cited Dronamraju, now Liu, Donlin Long, Reed Persuasion and Healing more than 1,600 times in the president of the Foundation Pyeritz, and Sir David Renato D. Alarcón, MD, MPH, literature, a prodigious ac- for Genetic Research in Weatherall. and Julia B. Frank, MD complishment,” write Renato Houston, contributed two The most charming (JHU Press, 2012) D. Alarcón, a Frank protégé, of the 17 essays recounting contributions of personal and Frank’s daughter, Julia B. McKusick’s professional ac- recollections were written by A half-century ago, Hopkins’ Frank, who became a psychi- complishments and personal McKusick’s wife of 59 years, Jerome D. Frank revo- atrist herself and collaborated characteristics. Francomano, rheumatologist Anne Bishop lutionized the perpetually with him on the third edition now director of adult genet- McKusick ’50 and his “DNA debate-riven and factionalized of his book. ics at the Harvey Institute identical twin brother,” Vincent field of psychotherapy with Marking the 50th anniver- of Human Genetics at L. McKusick, former chief the publication of his land- sary of Persuasion and Healing, GBMC—and part of the justice of the Maine Supreme mark 1961 book, Persuasion Alarcón and Frank have assem- research team at Hopkins Judicial Court. and Healing: A Comparative bled an impressive roster of 20 that in 1991 discovered the The book also contains Study of Psychotherapy. psychiatric scholars—including gene that causes Marfan eight eulogies, some delivered Frank (1909-2005), who Hopkins’ Paul R. McHugh syndrome—also contributed at McKusick’s funeral, including had come to Hopkins in 1940 and Glenn J. Treisman—to two essays. One of these one written by former School as a resident under Adolf bring a 21st-century perspec- was written in collabora- of Medicine dean Richard S. Meyer, systematically ana- tive to Jerome Frank’s insights. tion with the late David Ross. In addition, it features lyzed the effectiveness of the In 15 essays—six on the ba- Rimoin, a 1967 Hopkins a 29-page bibliography of multiple, fiercely competing sic principles of psychotherapy PhD, fellow, and house staff McKusick’s 172 scientific papers. theories of psychotherapy— and nine on current practices member who became a In his 18-page essay, “Victor numbered by one scholar at in the field—the contributors pioneering medical geneticist McKusick and the History of more than 500. update Frank’s central themes, at Los Angeles’ Cedars-Sinai Medical Genetics,” Sir Peter Employing carefully thoroughly critique the latest Medical Center. He died S. Harper (fellow, medi- devised, innovative experi- developments in psycho- last May. cine, 1973), former professor ments on the efficacy of these therapeutic methods, and offer The brief introduction of medical genetics at the conflicting psychotherapeu- proposals on how to improve to the collection was writ- University of Wales College of tic methods, Frank and his its practice. NAG

Hopkins Medicine • Fall 2012 • 13 | Bench Press | | Bench Press | defying d th Cells on a seemingly one-way road to dying have come backa from the brink, raising tantalizinge treatment possibilities for everything from heart attacks to cancer. By Christen Brownlee Illustration by Michael Glenwood

hen faced with death at Marooner’s Rock, Peter Pan bravely quips, “To die will be an awfully big adventure.” That’s because fatality is the ultimate of finalities. None of us knows for sure what happens after death, but most of us can be relatively sure that once we’re dying, there’s no turning back. WBut what if the road to death wasn’t as one-way as we’d previously thought? A new Hopkins study suggests that it may be possible to do a 180 from dying—at least, for cells. When scientists exposed batches of cells to deadly poisons, leaving them looking like they’d headed to that vast petri dish in the sky, the majority were still able to bounce back completely after those toxins were removed. Not only is this finding a testament to the indomitable cellular spirit, but it could also hold plenty of practical value. Better understanding this death-defying process may offer some practical insight on how to save dying tissues after heart attacks or , as well as prevent cancer in cells transiently exposed to toxins.

Hopkins Medicine • Fall 2012 • 15 | Bench Press |

Findings Too Wild to Believe controversy about what constitutes the point of no return for As in the Peter Pan novel, this new insight into death—or cells.” the lack thereof—got its start with a set of siblings. When Hogan Tang headed for Montell’s lab in 2009 to con- Ho Lam “Hogan” Tang began his first year as a doc- tinue his PhD, soon joined by Holly, who took a job as a toral student at the Chinese University of Hong Kong, his lab coordinator for Montell. Together, the team, along with younger sister Ho Man “Holly” Tang took a break from her additional colleagues at Hopkins, replicated the experiments undergraduate biology program at the Iowa State University performed in Hong Kong. The researchers exposed healthy and joined him in his research as a junior visiting scholar. cells isolated from mice or rats and growing in petri dishes Hogan’s main project was studying aspects of apoptosis, to ethanol, a potent toxin. Within hours, the cells displayed the process of programmed cell death, which scientists have the typical hallmarks of apoptosis, including cell body and known about for decades. nucleus shrinking, cell membrane blebbing (developing ir- Apoptosis can be both positive and negative. For example, regular bulges), and an altered appearance of cellular organ- cell death is absolutely necessary to sculpt fingers from elles. However, when the scientists washed the ethanol away, paddle-shaped hands during development and to kill off they watched in amazement as many of the cells plumped rogue cells that could be the start of cancerous tumors. How- back up, smoothed their membranes, and regained normal ever, it also kills cells in excess after traumatic events, such as organelles. a heart attack or , or in degenerative diseases, such as To rule out the possibility that only rare “escaper” cells Alzheimer’s disease. were somehow managing to dodge death, the researchers While trying to figure out how the cell’s cytoskeleton, counted how many made it. Their findings showed that a network of fibers that helps it retain its shape, remolds about 90 percent of the cells managed to survive. during apoptosis, Hogan and Holly Tang became curious “You can watch an individual cell shrivel up, look like it about whether the cells they had exposed to toxins to kick- has no chance, and then come back to life,” Montell says. start apoptosis were really on an irreversible track to death. The team published their findings online in April in the Scientists had long considered a set of physical and molecular scientific journal Molecular Biology of the Cell. markers—changes in a cell’s appearance, or the appearance Repeat experiments showed that the findings held true of the activated form of an enzyme known as caspase-3—as for a variety of cell types, Montell adds, including mouse unmistakable signs that a cell was definitively going gently brain and rat heart cells. This suggests that the ability to defy into that good night. death could be universal for all or at least many kinds of cells But when the Tang siblings saw the same things in their in the body, she says. Additionally, the team discovered that batches of cells, they weren’t so sure. reversing apoptosis wasn’t just something physical to observe “We were curious,” Hogan remembers. “We always do in the microscope. Gene expression data showed that several experiments together, and sometimes we have some weird molecular indicators that researchers had considered signs ideas. We thought, if it doesn’t cost a lot of time and money, of imminent death, such as activated caspase-3, also reversed we’d test whether these were really dead cells.” when the cells sprang back to life. In some preliminary experiments, the duo waited until Though part of the apoptosis program includes cells chop- the cells surely appeared to be pushing up daisies by the ping up their own DNA—part of a complicated self-destruc- hallmarks other researchers had established, then replaced tion sequence—further tests showed that they could snap the toxic brew the cells were sitting in with normal media, a back even from this genetic damage, stitching the severed nutritious broth that researchers ordinarily use to grow cells. pieces back together. However, more experiments showed Within hours, they noticed that most of the cells appeared to that sometimes cells made mistakes, missing pieces of DNA turn back, regaining their original appearance and behaving or connecting the wrong pieces. as if they’d never faced mortality. Since these kinds of errors can lead to cancer, the scien- Hogan Tang recalls that at their next progress seminar—a tists tested whether surviving cells exposed to toxins had forum in which a lab member can share his or her findings malignant characteristics. Sure enough, they found that a and get feedback from colleagues—no one believed their small percentage of the cells grew abnormally, developing results. A few months later, when he received a Fulbright some hallmarks of cancerous growth. scholarship and started contacting labs in the U.S. where he might go to continue his studies, he ran into the same Monsters or Prophets? problem. “They all rejected it,” he says. “They just weren’t Rather than cast a dark pall over this rejuvenation, that last interested, or they thought it was too wild an idea.” finding could have implications for explaining and treating But his luck changed when he contacted Denise Montell, cancer, as well as a variety of other diseases, Montell says. a professor in Hopkins’ Department of Biological Chemistry. For example, though researchers know that alcoholics have Montell was open-minded enough, Hogan recalls, to chal- a propensity toward developing liver cancer, the lenge what many researchers believed were central dogmas in have been unclear. Based on this discovery, it’s possible that apoptosis. problem drinkers might continually be bringing their liver “There’s clearly some point when something is truly dead cells toward the brink of death and that some surviving cells and can’t come back,” Montell says, “but there’s been a continue on with genetic defects that lead to malignancy.

16 • Hopkins Medicine • Fall 2012 “You can watch an individual cell shrivel up, look like it has no chance, and then come back to life,” says biological chemistry professor Denise Montell (center), with siblings Holly and Hogan Tang.

The results might also explain why cancer cells often Montell, the Tang siblings, and their colleagues plan to develop resistance to chemotherapy. During chemotherapy, continue to investigate the mechanisms behind this abil- cells are transiently exposed to toxic drugs that induce apop- ity to bounce back, which they’ve named anastasis, based tosis, and then the patient is allowed to recover. So while on research from two acquaintances, Ralph A. Bohlmann most of the cancer cells die, those that survive may develop and James W. Voelz, who happen to be Greek scholars. genetic defects some of which could contribute to their abil- While “apoptosis” comes from Greek roots meaning “fall- ity to resist death on the next round. ing to death,” “anastasis” means the opposite, “rising to life.” In effect, the finding could offer new hope for a variety Knowing more about this process could eventually lead to of conditions that center around cell life or death, says Allan ways to enhance it, Montell says, which could be a boon for Spradling, director at the Carnegie Institution for Science conditions in which apoptosis occurs to excess. On the other in Baltimore. “Do resurrected cells become monsters that hand, identifying ways to reduce or prevent anastasis could continue to lurk in an organ’s dark corners, or prophets that be useful for averting the development of resistance to che- can rally neighboring cells to carry out novel and beneficial motherapy or other conditions where cell survival is harmful. actions? Either way,” he says, “the new knowledge generated By helping cells live or die, she adds, researchers might by these investigators may soon improve our ability to man- eventually help people get back to their own healthy lives— age some of the diverse medical conditions that are expected an awfully big adventure in itself. to generate [these] cells.” * “Do resurrected cells become monsters that continue to lurk in an organ’s dark corners, or prophets that can rally neighboring cells to carry out novel and beneficial actions? Either way, [this] new knowledge may soon improve our ability to manage some of the diverse medical conditions that are expected to generate [these] cells.” —Allan Spradling, director at the Carnegie Institution for Science

PHOTO BY Chris Myers Hopkins Medicine • Fall 2012 • 17 Comfort zones Palliative care advocates are taking hospice strategies and pushing them “upstream”—to aid patients throughout the course of a serious illness. By Jim Duffy Photos by Monica Lopossay

18 • Hopkins Medicine • Fall 2012 Louise Moyer and her husband, John, were able to make the most of his final months, thanks to a palliative care team at Hopkins.

Comfort zones

Hopkins Medicine • Fall 2012 • 19 By the time she found her way to someone who knew about palliative care, Louise Bianco Moyer was in a desperate state. Her husband, John Moyer, was fighting a long, brave battle with two primary cancers—the first, in his kidney, appeared in 2006, while the second, in his rectum, showed up in 2010.

A facilities engineer at the Patuxent Naval Air Station in palliative care here,’” she recalls. In fact, Cooper herself is a Southern Maryland, John was faring tolerably well when part of the interdisciplinary team providing care at Kimmel as things took a turn for the worse in mid-2011. His weight bal- the Harry J. Duffey Family Pain and Palliative Care Program. looned, and he was soon carrying more than 300 pounds on Cooper reached out to her colleagues on the Duffey team, his stocky, 5-foot, 8-inch frame. Of even more concern was and the next day a physician and nurse arrived to consult on the pain shooting down John’s legs; over time, it became so John Moyer’s case. “We found a person in terrible pain—John excruciating that it left him all but incapacitated. was just miserable,” says the nurse, Lynn Billing. The guy Louise had fallen in love with was a larger-than- Moyer’s other physicians had been uncomfortable about life figure. “If you walked into a crowded room where you increasing his doses of pain medicine past a certain point, but didn’t know anybody, John’s the guy you’d notice right away,” the palliative team recommended that they try doing just that. she says. “He was just filled with the joy of living. He had a They converted the pain medications he had been receiving to huge appetite for everything human—food, fun, sex, friends.” an intravenous hydromorphine, Dilaudid, and they escalated The John before her now was a shadow of that man. At just the dosage until Moyer’s comfort level increased. 48, he had none of the joy that so defined his healthy life. Ev- Within a few days Moyer was planning a bass-fishing trip ery ounce of his strength was spent grappling with that pain with friends—in Florida. “I cannot even begin to say what a in his legs; he had nothing left in reserve. difference they made in my life—and in my husband’s life,” No one was able to help. Specialist after specialist in mul- Louise Moyer says. “I finally had my husband back again.” tiple hospitals ran test after test. Time and again, they failed to find a cause for John’s woes. “It looks like your husband is fine—we can’t find anything wrong,” said the doctors. While palliative care can trace its When Louise Moyer recalls such moments, her voice shakes roots back centuries to the work of religious orders in Eu- in tears one moment, then rises in anger the next. She was rope, the modern incarnation of the field dates only to the certain the experts were wrong, but everything she tried or late 1980s. That’s when Cleveland Clinic and the Medical Col- suggested added up to nothing more than grasping at straws. lege of Wisconsin began dipping toes in patient-care waters, Louise has a sister in Michigan who’s a nurse, and she inspired by the hospice movement but no longer limited to mentioned the possibility of palliative care—a fast-growing patients who are knocking on death’s door. specialty that is focused on providing value-added treatments The field has been growing rapidly ever since. Lynn Billing and services that aim to help patients feel healthier and live is the nursing coordinator on the Duffey team at Hopkins. fuller lives even while they battle serious disease. When she first attended the annual conference of the Ameri- After her husband became an inpatient at Johns Hopkins can Academy of Hospice and Palliative Medicine, there were Hospital, Louise asked about palliative care but was told at about 500 colleagues in attendance—that was in 2005. This first that the service was unavailable (and indeed, at that point, year’s conference drew seven times as many. the service was only available in targeted wards). A short while The national Center to Advance Palliative Care has tracked after that Louise found herself meeting with Rhonda Cooper, the spread of the specialty into hospital settings. By 2000, the chaplain at the Sidney Kimmel Comprehensive Cancer roughly one in four U.S. hospitals had started some sort of pal- Center. liative care initiative; 10 years later, that had climbed to nearly “I told her everything, the whole incredible story of all the two out of every three hospitals—some 1,600 institutions. things we’d been through and why I just didn’t trust anybody But the field still has a way to go. One sign of just how far anymore,” Louise says. “Rhonda just sat there with me, listen- is the way some medical professionals still seem a little unclear ing, and the whole time the tears were just pouring out of me.” about what, exactly, palliative care is. The Duffey program has Cooper remembers the encounter clearly. “Some people been up and running for five years now, but on occasion the think chaplains only get called in when someone is about to team still encounters misconceptions. die, but that’s a misconception,” she says. “Most of my work “The most common is that we’re only about end of life, or is with people who are in distress. Not just patients but also that palliative care and hospice are one and the same,” Billing spouses and other family members, and staff as well. What I says. “We hear from colleagues—‘No, this patient isn’t ready try to do at first is just listen very deeply to what they’re will- for you.’ Our response is, ‘We want to be helpful,’ and we start ing to share.” by meeting the patient and family where they are.” Cooper was surprised to hear Louise complain that Hop- The dictionary describes a treatment as palliative when it’s kins didn’t offer palliative care. “I said, ‘Oh yes, we do have aimed at symptoms rather than a disease. So in one case a

20 • Hopkins Medicine • Fall 2012 palliative team might work alongside an oncologist to reduce experts in the field. His appointment marks the first full -em pain and ease nausea through a chemotherapy regimen. In brace of the young specialty at the institutional level. another, the team might treat a patient’s depression or help On a recent Thursday afternoon, Smith joined with 15 of him navigate the spiritual crisis that arises so often in serious his colleagues as they squeezed into a small conference room illnesses. Then there are cases where the team is focused on just off the lobby of the Kimmel Center for a meeting of the making sure patients are able to manage the home environ- weekly Multidisciplinary Cancer Pain Conference. ment and thrive as outpatients. The case that dominated the meeting involved a woman The palliative toolbox, then, includes the skills of physi- with metastatic melanoma who’d endured multiple recent hos- cians, nurses, pharmacists, , chaplains, social pital admissions. The animated discussion was focused on how workers, and more. This array is quite similar to the toolbox to ease the woman’s pain to the point where she could stay used in hospice—the key difference is that palliative care ad- at home for an extended stretch with her husband and grade- vocates have their sights set on helping patients not just when school-age child, without bouncing back into the hospital. death is imminent but throughout the course of a life-threat- A key strategy under consideration is one that’s been highly ening illness. They’re taking hospice concepts and pushing successful in such cases—delivering pain medications directly them “upstream.” into the spinal fluid. The team also discussed a number of A 2010 study at Massachusetts General is often cited to symptoms beyond pain, including depression, shortness of demonstrate the potential of the field. There, researchers breath, and fatigue, among others. randomized 151 patients with metastatic non-small cell lung As the discussion wound down, Smith raised a hand in cancer into two groups at the time of diagnosis—one group the air and moved the subject to the woman’s long-term pros- got standard oncology care, while the other received pallia- pects. Asking about prognosis, he learned that the patient is tive care in addition. The palliative patients experienced the likely to die in the window of six months to one year. boost in quality-of-life measures that such care is designed to “Has anyone been in yet to say, ‘What do you want to know deliver—less depression, less pain, fewer complications. They about what’s going on with your illness and where things are also lived on average almost three months longer than those in headed?’” he asks. “If she wants to know more, this is the time the control group. The results helped convince the American to be honest. It’s going to go a lot better if we do that now so Society of Clinical Oncology to issue a formal recommenda- that she and her family can get to thinking about it sooner, tion last year that diagnosis is the right time to start delivering not when she’s at death’s door. Can we help her get started palliative care to such patients. with a life review? Maybe she’ll want to write things down for her child.” Trained as an oncologist, Smith knows from experience At Hopkins, the first palliative care initiative sprang that in treating patients suffering from a deadly disease, there up as a small consult service in the Department of Medicine can be lots of seemingly sound reasons to steer clear of frank in the late 1990s. Then came the Harriet Lane Compassion- discussions about a bleak prognosis. Is this patient at risk for ate Care program at the Children’s Center, which started as a depression? Does that one seem likely to give up the fight alto- staff educational initiative. Later, the Duffey program at the gether? Is a third dependent on the support of family members cancer center grew out of an existing pain service; it, too, is who might not be able to handle the news? structured as a consult service giving recommendations to “It turns out that it’s a bit of a myth that oncologists like care teams. me actually sit down with patients at some point and have These efforts tended to be small and underfunded, says these ‘big’ conversations,” he says in an interview. “Some of us Terry Langbaum, chief administrative officer at the Kimmel do, but a lot of us don’t.” Center and a longtime cham- That’s not just an an- pion of expanding palliative care The Compassionate Care program at the Children’s ecdotal impression. Smith at Hopkins. “Over time we be- Center aims to help families enjoy a child for every cites one study in which re- came an outlier among academic moment that they have together, says medical searchers looking back over director Nancy Hutton (right), with program medical centers,” she says. “In a director Cynda Rushton. patient charts found that field that was young but growing such “big talks” happen in and obviously catching on every- just one of five cases where where, we were falling behind. the patient is likely to die. That’s not supposed to happen Smith cites another study here—we’re Hopkins.” at one academic medical That began to change late center, where in just two last year when Thomas Smith of 85 such cases did oncolo- was named the first-ever direc- gists raise with patients the tor of palliative care for Johns topic of preparing advance Hopkins Medicine. He arrived health care directives to in East Baltimore from the Vir- guide care. ginia Commonwealth University In that sense, there’s a School of Medicine (formerly the bully-pulpit aspect to the Medical College of Virginia), job at hand for Smith and where he had established himself his colleagues. Hopkins as one of the nation’s foremost is built upon the curative

Hopkins Medicine • Fall 2012 • 21 power of medicine. While the growth of palliative care doesn’t Such deaths are more costly than they should be on just change that goal, it does ask physicians who are often strapped about every front. Patients miss out on opportunities to savor for time and resources to deliver Hopkins-level excellence priceless moments, whether that’s making amends with an es- along a parallel, palliative path. tranged sibling, confiding in a minister, or dying at home with “It’s a major leap in this institution,” says Langbaum. “Our loved ones close at hand. docs can always pull some rabbit out of a hat. You know, if Those loved ones miss out on such moments as well. And, this treatment fails we have that treatment and if that fails Smith notes, they find themselves in the aftermath of their there’s a third and after that there’s a clinical trial. They’re loss at higher risk for depression and post-traumatic stress scientists, and their focus is on curing the disease.” compared with families whose loved ones receive palliative Smith points to a series of research results showing that the and hospice care. Hospice families are also less likely to go fears clinicians have about “big” talks are misplaced. The vast bankrupt, Smith says, and surviving spouses are less likely to majority of patients with deadly diseases tell researchers that die in the aftermath of their loss. they’d prefer it if caregivers spoke early on and frankly with The health care system loses out as well. Deaths are much them about their prognosis. more expensive in intensive care than they are in hospice. Smith himself helped conduct a study that found that in Here, Smith cites a test project by the insurance company the absence of such discussions many patients came to believe Aetna to deliver palliative care alongside standard treatment their prognosis was worse than it actually was. in terminal cancer cases: The costs of care in the last 40 days “We also measured their sense of hope—it’s the first time of life dropped by 22 percent, primarily due to reduced hos- anybody studied that around a prognosis,” Smith says. “And pitalizations. the level of hope those patients felt about their future didn’t “No one got into this field with the first thought in their diminish after they had all the facts—it either stayed the same mind being that it might be a great way to save money,” Smith or went up a little bit. And depression is far less likely when says. “But the fact that palliative care allows people to live we have these discussions, for both patients and caregivers.” longer and live better while also saving money—that’s obvi- “When this doesn’t happen,” Smith says, “that’s how we ously a good thing considering what’s going on with costs in end up in these worst-case scenarios where we have patients the U.S. health care system.” we know are going to die, but we end up giving them no Concrete plans are now in place for the expansion of pal- chance to prepare before they end up in intensive care, hooked liative care at Hopkins. An inpatient palliative unit is slated up to blood pressure support and suffering from things like to open next year on Marburg 3, Smith reports, that will serve delirium and other complications.” patients in need of symptom “tune-ups” as they’re discharged

Most patients with deadly diseases prefer for caregivers to speak early on and frankly about their prognosis, notes palliative care director Thomas Smith, with nursing coordinator Lynn Billing. ‘‘The first thing we did was to conduct a needs assessment, and the thing we learned is that our clinicians were suffering a lot around these issues of end-of-life care. There was grief and moral distress.’’ —Cynda Rushton, Program Director

from the emergency room or intensive care. At the Children’s conferences that put the entire range of caregivers at the table Center, palliative care experts are in the midst of business to discuss goals of care and debate treatment options. And planning and developing a campaign to seek philanthropic they developed a new system of debriefing sessions for staff support for the expansion of such care there. with the center’s bereavement counselor in the wake of patient deaths. “Over time there was a genuine change in the air,” Hutton As medical director of the Harriet Lane Com- says. “Before, it was like the ‘wounded healer.’ There were pro- passionate Care program at the Children’s Center, Nancy fessionals here experiencing loss and doubt without ever ac- Hutton is often called in to consult on cases where children knowledging it to themselves or anyone else. After, there were have a bleak prognosis. Whether they are likely to die in a few more open conversations about the fact that children here can months or over a longer time frame, the care she delivers often have a bad prognosis. It became safer to talk and debate about tends to be as much focused on the arts of communication the best things to do when that’s the case.” and compassion as it is on clinical recommendations. That groundwork helped the field build up credibility, so In a recent case, Hutton watched as a young mother hop- much so that it was the Children’s Center staff who came to ing for good news received instead the worst possible report the Leadership Council and requested that it create a consult from her child’s doctors. In the weeks that followed Hutton service. That service began operating in 2009, but is not yet and other palliative caregivers made a series of home visits that funded in ways that would provide 24-hour access, as well as helped build a foundation of knowledge about the family’s outreach to patients during clinic visits and at home. circumstances and trust with the child’s mother. “There isn’t so much of that misconception anymore that “Part of what I did with the child’s mother privately at the this is about hanging crepe,” Hutton says. “People see that it’s bedside is say things like, ‘There’s going to come a time when about doing our best to help families enjoy a child for every someone’s going to ask you really hard questions, and you moment that they have together.” need to think about what your answers are going to be,’” Hut- ton says. “There’s going to come a time when the stomach isn’t working anymore. There’s going to come a time when seizures John Moyer spent most of April and are out of control. I told her, ‘We’re not there today, but there’s May of this year back home, his pain lessened and his outlook going to be a day when you’re asked whether your child should improved. Looking back, his wife cherishes every moment of stay on the breathing machine.’” those calmer weeks after all of the time spent bouncing in and The Compassionate Care program developed along a path out of hospitals. that’s unusual in the field. Most palliative services start out The Moyers came into Hopkins on June 4 to discuss a on a consult model like the Duffey program at the Cancer planned surgery to ease some digestive blockage John was Center. The Lane program dates its history to 1997, but direct experiencing. Instead, the couple found themselves meeting consultations on cases began only three years ago. with nurse Lynn Billing in a private room. There, Billing re- “The first thing we did was to conduct a needs assessment, viewed the latest report from John’s physicians, explaining and the thing we learned is that our clinicians were suffering that his cancer had exploded and was now out of control. a lot around these issues of end-of-life care,” says Program Di- “She said he had about three weeks left, and he died three rector Cynda Rushton. “There was grief and moral distress.” weeks and three days later,” Louise Moyer says. Often, Rushton adds, such distress revolves around heart- Later that day, Billing spent two and a half more hours wrenching questions that arise in cases where children are not with the Moyers, first with both husband and wife and then going to survive their illnesses. What should the primary goal with Louise alone. “She had such a marvelous way of present- of treatment be? Are we striking the right balance between ing what we needed to do on the next step,” Louise recalls. “It trying to extend life for days or weeks and trying to boost wasn’t like we were giving up—we were shifting our focus and quality of life so that families can make the most of their we were going to spend our energy to die well.” remaining time with the patient? Occasional disagreements John died on June 28, assisted by a hospice program in among caregivers around such questions are inevitable—and Southern Maryland. In the wake of her experience, Louise the high stakes involved can generate emotional tensions. has become a strong advocate for palliative care. So, at first palliative care efforts at the Children’s Center “We live in a society where no one wants to talk about focused on staff more than patients. The center’s volunteer- death, and when you think about it that’s the one thing we driven Compassionate Care Leadership Council initiated a all have in common,” she says. “The people in palliative care new series of palliative care rounds on units where staff dealt aren’t afraid to talk about it. Lynn and Dr. Smith just made most often with deaths. The council made it easier to convene such a difference in his life, and in our lives.” *

Hopkins Medicine • Fall 2012 • 23 24 • Hopkins Medicine • Fall 2012 The Last

WordPaul McHugh and colleagues are? on a crusade to radically rethink the manual that has come to define psychiatry. By Mat Edelson Illustration by Nigel Buchanan

Hopkins Medicine • Fall 2012 • 25 It is a book both revered and mocked by those within the profession—a 943-page diagnostic tome that was never intended to be a bible, yet nonetheless has been elevated to Final Word status by the majority of the nation’s practicing psychiatrists. It is not apocalyptic to state that the future status of the profession, its perceived capacity to help versus harm, may well rest on the book’s next chapter…

…So perhaps it’s only appropriate that, with the Fifth Psychiatry. “We had to come up with a classification system, Edition of the Diagnostic and Statistical Manual of Mental to get the psychiatrists to all agree on what disorders looked Disorders (a.k.a. DSM) on the verge of descending from like so they could at least call them the same thing.” the mountain top, a former DSM acolyte-turned-heretic is Enter DSM III. Released in 1980 by the American Psy- leading his disciples away from the dogma, and toward what chiatric Association (APA), it was staggering in scope: The he envisions as a promised land where mental illness and its work of hundreds of psychiatrists yielded symptoms for 265 sufferers will be seen and treated in a healing new light. diagnoses—for illness ranging from borderline personality disorder to catatonic type schizophrenia. Yet hardly any of the diagnoses had established scientific “validity,” i.e., a veri- o understand Paul McHugh’s love/hate fiable base set of causes, notes McHugh. This initially greatly relationship with the DSM is to understand concerned him. the history of the book itself. Actually, it was “I told [DSM-III editor] Bob Spitzer, ‘Gee, Bob, I don’t more of a short synopsis in its first two incarna- know; you’re starting off by naming stuff whose nature you tions, circa 1952 and 1968—nascent attempts to don’t know,’” recalls McHugh. “And he said, ‘Nope, Paul, categorize and nomenclate the expressions of this is the way to do it.’ And for the first 10 years after, I Tmental distress. But by the early-70s, it was becoming clear thought, ‘he’s right!’” that psychiatrists, depending upon their particular schooling McHugh, who was always fascinated by methods—he and inclinations, couldn’t agree on diagnoses; their infight- calls them “perspectives”—for helping to determine causa- ing was reminiscent of the Islamic parable of the Six Blind tion for mental illness, hopped on the DSM III train because Men and the Elephant, who, depending upon what part of of its implied promise: If psychiatrists, regardless of training the creature they touched, concluded that the animal defi- and practicing philosophy, could agree on which symptoms nitely was either a wall, spear, snake, rope, fan, or a tree. led to the same diagnosis, then researchers would have a There was nothing amusing about the diagnostic in- standardized field of patients to study, and begin to uncover consistencies then facing psychiatry. A landmark study in the base causes of different mental illnesses. This was vital, 1971 showed that, when evaluating patients with identical for while different methods of psychological therapy had symptoms, American psychiatrists generally concluded the long been studied, the root causes of what made people men- patients had schizophrenia, while British psychiatrists leaned tally ill in the first place, and how best to choose between toward a diagnosis of major depression. Two years later, a medications, therapy, and perhaps social services for treat- study in Science went a step farther; researcher David Rosen- ment options, had received far less attention. han sent volunteer “pseudo-patients” claiming audio hal- DSM III was supposed to fill this research Q and A void, lucinations into a dozen psychiatric hospitals across the U.S., but that’s not what happened in the wake of its launch; psy- where they were all admitted, some for weeks, with a schizo- chiatric research still lagged as few diagnoses proved easy to phrenia diagnosis. The hospital’s diagnostic criteria never pin to a single biological cause. Furthermore, the intention- ferreted out the fakers among their general schizophrenic ally atheoretical underpinnings of DSM III meant that “by population, leading Rosenhan to conclude, ominously, “It is rule, the APA’s editors wanted to stay away from thinking clear that we cannot distinguish the sane from the insane in about causes,” says Hopkins Kostas Lyketsos. psychiatric hospitals.” Meanwhile, the simplified “checklist” system of DSM Similarly, depending upon whether one landed upon III—which, critics say, tried to quickly nail down a symp- the doorstep of a Freudian, Jungian, behaviorist, or neuro- tom/diagnosis match using leading questions, without deeply biologically-oriented psychiatrist, one could be diagnosed investigating the patient’s bio/psycho/social history—was with a myriad of mental conditions requiring a plethora of radically transforming psychiatry. As an example, McHugh different treatments. This lack of agreement on diagnosis— mentions grief. In the wake of DSM III, it became classified “reliability” in medical parlance—was rapidly becoming an as major depression, “so instead of [doctors] talking with the embarrassment to practicing psychiatrists. person about the meaning of their loss, they just started pop- “The field was riven by ideological factions,” recalls ping pills into them. They lost touch with the humanity of McHugh, who directed the department from 1975 to 2001 this most basic human .” and is now University Distinguished Service Professor of Still, the checklist concept was proving irresistible: Within

26 • Hopkins Medicine • Fall 2012 a decade the APA found itself with a multimillion dollar diagnostic labels on seemingly “normal” people, the medi- bestseller on its hands, as both psychiatrists and physicians calization of kids to the point where 2-year-olds were being outside the field became fascinated by this elaborate diagnos- diagnosed and medicated for depression … this was a cat- tic menu. echism McHugh could no longer embrace. “DSM III was meant as a tentative guide to diagnosis. Especially because he had already found a better way. Instead, it was treated like a bible,” says McHugh contem- porary Allen Frances, who was editor of the 1994 DSM IV before becoming one of the fiercest public critics of the direc- n the May 17 issue of the New England Journal tion the latest DSM edition is taking. “People never took of Medicine, McHugh and Hopkins colleague Philip seriously DSM I and II. But the [symptom] sets of DSM III Slavney laid their concerns over the coming DSM became the subject of cocktail party conversation, they be- revision on the line in an essay titled “Mental Illness— came the subject of research, they became the way insurance Comprehensive Evaluation or Checklist?” Lead author companies paid for treatment. It decided who was sick and McHugh didn’t mince words: “Identifying a disorder by who wasn’t. It became the vehicle for determining disability Iits symptoms does not translate into understanding it. Clini- benefits and who would get school services. And it was very cians need some heuristic concept of its nature, grasped in important in the courtroom. But each time the DSM was terms of cause or mechanism, to render it intelligible and to used beyond its capacity, the use distorted itself and the place justify their actions in practice and research.” it was being used. It was meant to help psychiatry retain its Leading members of the APA, well aware of the criticism credibility, but no one realized there’d be this vast over- of the DSM levied by McHugh and others, argue the latest shoot.” version will be able, thanks to electronic publishing, to re- By the time DSM-IV rolled around in 1994, Paul spond to and potentially correct areas of diagnostic concern McHugh believed that his field was in trouble. The DSM within the tome. “I don’t like the term ‘bible,’ says David had led everyone to believe they could practice psychiatry: Kupfer, who is lead editor for the current revisions. “A bible Consider that, with the help of big pharma’s “if you have is written once, and we can write commentary on it, but we these symptoms, ask your doctor” ads, nearly 80 percent of can’t change it. I think it’s important to convey the fact that all psychiatric meds were being prescribed by internists and this DSM is going to be a living document. We’re calling it family practitioners—some in the course of a seven-minute DSM 5.0; we see a 5.1, 5.2, and a 5.3, not rewriting the whole HMO visit. Hardly time to deeply evaluate a diagnosis, let thing, but where there is new information, and good thresh- alone get to the cause of the problem. olds met to change criteria, we want to be able to do that and And it was that explosion of new diagnoses that most not have it wait in the queue for 20 years.” concerned McHugh. DSM IV contained nearly 300 diagno- McHugh, who maintains a cordial relationship with ses—three times more than DSM I. “In the early ’90s, things Kupfer, respectfully disagrees on waiting to implement dawned on me. These diagnostic categories that the experts change. His solution—or at least a suggestion of where DSM said existed were expanding way out of size. [Patients] only 5 should head immediately—is a direction that ironically express [themselves] emotionally in so many ways; ultimately harkens back to psychiatry’s roots at Hopkins of nearly a doctors began to put lots of people in the anxiety category century ago. That’s when Adolph Meyer established the first and the major depressive category, and they were all get- comprehensive methods for evaluating a patient’s life—the ting the same kind of treatments,” says McHugh. He also origins of the bio-psycho-social model. believed the DSM was allowing faddish diagnoses to get in That was supposed to be DSM’s 21st-century model as without scientific rigor. well. But even the APA’s then president Steve Sharfstein “DSM [inclusion] gave cover to certain kinds of major admitted in 2005 that his field had turned into “a bio-bio-bio assumptions, such as the ‘recovered ’ and ‘multiple model” dominated by “a pill and an appointment.” personality’ syndromes. As soon as you said in the DSM For McHugh, such an approach is anathema to the way that multiple personality exists, then people could build up he’s taught the psychiatric arts to thousands of Hopkins treatment programs based on the fact that you repressed medical students over the past 40 years. While it’s impossible of sexual abuse as an infant. And they went wild for students to ignore the DSM—at the very least, it guides on that,” says McHugh, whose 2008 book Try To Remember insurance reimbursements that sustain medical practices— recounted his and other psychiatrists’ mostly successful ef- McHugh says the DSM is best seen by students as a general forts to discredit the existence of both conditions. field guide to psychiatry, much in the same way amateur bird The price of devotion was becoming too high for watchers might look at an Audubon guide to separate robins McHugh; the harm to families victimized by accusations from starlings. of false memories of abuse, the infliction of stigmatizing But to really figure out what makes starlings or people tick—or at least get them flying toward their own personal True North again—McHugh and Slavney’s teachings have balanced the DSM’s black-and-white influence with their version of modern day Meyerism, which they’ve written about in The Perspectives of Psychiatry. First published in 1986 (a second edition came out in 1998), the book urges psychia- trists to invoke four perspectives with each patient to get to the heart of their condition. The book is considered the foundation of Hopkins clinical training, and its influence

Hopkins Medicine • Fall 2012 • 27 has reverberated across the field. “It is a book for the ages,” says Margaret Chisolm, who “We’re saying, after a directs psychiatric education at Bayview and was schooled in McHugh’s methodology. “They call it the recipe for ap- generation of description, plying the bio-psycho-social model.” Duke’s Allen Frances you’re going to bring out a has an equally humanistic view of McHugh’s perspectives: “ [says] it’s far more important to understand the new edition and the only thing person who has the disease than the disease the person has. Paul’s [perspectives] are following in those footsteps,” says you’re going to tell us is you’ve Frances. discovered a few other If it were up to McHugh, the perspectives would become a new organizational structure for both the DSM and the diagnoses? You don’t need a field at large. They include categorizing diagnoses by: • Brain Diseases, such as schizophrenia new field guide, if that’s the • Personality Dimensions, such as obsessive-compulsive best you’re going to do. disorder • Motivated Behaviors, such as alcohol and an- The time has come to move orexia • Life Encounters, including grief and post-traumatic stress toward explanation.” disorder —Paul McHugh To the layperson, such perspectives appear at first glance to be both subtle and contradictory. Neuro-psychiatrists might suggest that all mental illness is caused by brain disease. Similarly, in a sort of chicken-and-egg conun- drum, does someone with anorexia not eat because they are obsessive-compulsive, or does the desire to not eat become obsessive over time? To McHugh, this is where the monochromatic current viewpoint of the DSM has to yield to the investigation, reflection, and consideration of numerous causal factors that can be brought forth by applying the perspectives to each psychiatric patient. Instead of a rush to diagnosis, the em- phasis becomes about understanding, insight, and appropri- ate treatment. Each perspective is brought to bear, like applying rotating gel lights of different colors to the same stage. Subtle? Yes. Field changing? Perhaps. It’s worth noting that, in a journal noted for vigorous debate, there was no rebuttal from the APA or others to the McHugh/Slavney call-to-arms. If any- thing, some of the country’s top psychiatrists are embracing his message. “I think Paul’s perspectives nails it,” says University of Iowa psychiatrist Arnold Andersen, an eating disorders authority who spent 15 years at Hopkins working with McHugh. “They address the issue by recognizing that differ- ent modes of reasoning are needed to appreciate the real-life, categorical differences between different types of psychologi- cal distress. “Take alcohol abuse,” continues Andersen. “It’s a behavior with different sources. There isn’t any one treatment until you trace back the origin. The little old lady who has sherry before her Canasta game to calm a benign hand tremor is very different from the 13-year-old who just loves alcohol and has no side effects [that’s almost always genetic] and from the person who uses alcohol to cope with a high-stress situation. To categorize those three on a single checklist implies the job is done. “By contrast, Paul’s approach is the soundest I know. The perspectives have a methodological approach; when he finishes with a global assessment [of a patient], you have a comprehensive guideline on how to begin with treatment. If

28 • Hopkins Medicine • Fall 2012 DSM 5 would put their different disorders into his categories, DSM definitions. That education did not draw anyone into you could begin to reason in a far more sound way.” the field.” “I have eight pages on Paul’s system,” says Harvard psy- Even with a serendipitous mentor or attending physician chologist Jerome Kagan, referring to his own book, Psychol- who can see beyond the DSM and excite a student about ogy’s Ghosts: The Crisis in the Profession and the Way Back psychiatry, many young doctors arrive at Hopkins after (2012). To Kagan’s thinking, while McHugh’s first three medical school—or even residencies—completely dependent categories can all lead back to biological roots, “Family four upon the manual. was his brilliant idea; that any of the symptoms in families Kotsas Lyketsos, chairman of psychiatry at Johns Hop- two [personality dimensions] or three [motivated behaviors], kins Bayview, worries that this can draw the wrong people can have mainly environmental causes.” to the field. “The DSM gives the appearance that psychiatry “Consider,” Kagan says by way of example, “that the best is easy, so people who are interested in basic research would predictor, right now, in any part of the world, of whether be happy to come through psychiatry, learn the checklist, get you’re going to have anxiety, depression, impulsive aggres- the imprimatur of being a psychiatrist [with no intent of en- sion, gambling, or drug abuse is the social class in which you gaging clinical practice], and not really learn what it’s really grew up.” By solely using DSM, social status might never be like to think through a problem facing a patient.” discussed on the way to, say, a diagnosis of depression with What Lyketsos and colleague Margaret Chisolm are resulting treatment being anti-depressive drugs. However, doing is taking McHugh’s perspectives one important step using McHugh’s approach that considers environment, the further—to a place that they hope will attract more medical diagnostician might uncover that the onset of the patient’s students to psychiatry. McHugh’s textbook on the subject is depression coincided with his being laid-off six months considered a masterwork, notes Chisolm, but it’s not easily previously, and part of the long term therapy might include digestible for students relatively new to the game. The joy engaging social workers to help the patient find employment. has always been in listening to the entertaining McHugh McHugh also notes the perspectival approach could be speak, she says. This oration was the most accessible way to used by family practitioners to help them better evaluate pass along his insights about the perspectives to students. It which conditions can be handled comfortably in an inter- fell upon Lyketsos and Chisolm to set the sermons in stone, nist’s office—especially given their longtime familiarity with or as Lyketsos jokes, given his Grecian upbringing, “we had most patients—and which should be referred out to psychia- Homer; what we needed was the Iliad.” trists, who in many cases could work with the internists to Their new book, Systematic Psychiatric Evaluation, seeks help diagnose and best manage care. for the first time to put rules to McHugh’s perspectives and McHugh said he wrote the NEJM essay because, after give diagnosticians more confidence in their global assess- more than a generation of teaching the perspectives he ment and treatment of patients. “Rule number one is, you wanted to give them a public airing, especially in light of the want to take a complete history, and there are certain ele- development of DSM 5, which has been in the study group ments that go into that. You want to ask general questions phase since 2004 and is set to be released next year. Given that are not directing the answers,” says Lyketsos. “Re- that, as he notes, the APA will “make millions in royalties” member, in DSM you can’t do that; in DSM you’re directly from the publication of DSM 5, it would be a “failure of asking questions that say ‘do you have this symptom or that leadership” if the book is identical in scope to the previous symptom?’ So if you were strictly applying just DSM, you two that focused exclusively on descriptions of illness. “Every could not ask open-ended questions.” discipline has a right to go through a descriptive phase. We’re In the end, what Lyketsos, Chisolm, and McHugh are not blaming anybody for that,” says McHugh. “But you looking for in future psychiatrists is—well, there’s no other begin to criticize [leadership] when they say they can’t move word for it—perspective. It’s not about throwing out the out of the descriptive phase. We’re saying, after a generation DSM. “It drives treatment authorization, so you need as a of description, you’re going to bring out a new edition and practitioner to learn enough about it to use it, just as long as the only thing you’re going to tell us is you’ve discovered it doesn’t drive patient care,” says Lyketsos. Instead it’s about a few other diagnoses? You don’t need a new field guide, if emphasizing the “perspectival approach” to best guarantee that’s the best you’re going to do. The time has come to move that every appropriate treatment option can be explored. toward explanation.” Will the approach ultimately find its way into DSM 5? Probably not, given the publication’s deadline of 2013. But by going public with his critique of the DSM process, McHugh or as much as the DSM is being debated for is no longer a lone voice in the wilderness. its impact on patients, far less chatter surrounds the “Paul is a man of conscience and courage,” says Frances, effect it has on medical students and residents at in- who criticized DSM 5 because of his concerns that proposed stitutions where it is treated as The Book. McHugh expanded new diagnoses could, as he wrote in a New York strongly believes that such “training to the test”’ has Times op-ed in May, “define as mentally ill tens of millions the effect of driving would-be psychiatric residents of people now considered normal.” Finto other fields. “Paul is part of the inspiration of me [writing publicly] “The textbook education using just the DSM does such an about this stuff,” says Frances. “It’s not really part of my per- injustice to the field,” says second-year Hopkins psychiatric sonality to be a crusader, but he’s an example that you can’t resident Rachna Hundal. Her own medical school psych just sit on the sidelines.” rotation in Philadelphia, she says, “was just about DSM. We Not while there’s work still to be done. were taught based upon DSM definitions. Our exams were *

Hopkins Medicine • Fall 2012 • 29 In his quest to find answers to his daughter’s genetic condition, Hugh Rienhoff ’82 has gone “rogue”— and become a minor celebrity in the world of do-it-yourself biology.

By Sharon Tregaskis Photos by Leah Fasten The Bea Project

30 • Hopkins Medicine • Fall 2012 Hugh Rienhoff gives Bea a lift, in the backyard of their Bay Area home.

The Bea Project

Hopkins Medicine • Fall 2012 • 31 With the air of a mini-docent, Bea Rienhoff stops short in front of a prehistoric shark’s jaw at Baltimore’s National Aquarium. “A whole family can fit inside!” she declares. She and her older brother MacCallum have spent all day touring Charm City as their dad, Hugh Rienhoff ’82, met with former colleagues, research collaborators, and Bea’s doctor, Hal Dietz, the Victor A. McKusick Professor of Genetics at the School of Medicine.

Later, as they walk along the Inner Harbor, Hugh keeps an underpinnings of Marfan. During training, Rienhoff himself eye on his slight daughter, who’s clearly losing steam. “Do had examined dozens of adults with the condition, which is you want a ride, Bee Bee?” he offers, effortlessly sweeping caused by an anomaly in the transforming growth factor-ß her up. Off her feet—clad in black sneakers to anchor the pathway responsible for connective tissue and musculature. orthotics that support her arch and stabilize her ankles—she When Rienhoff left Hopkins in 1992, it was for a stint as perks up and Rienhoff regales the kids with tales of his ad- a managing partner at the Baltimore office of New Enter- ventures in the neighborhood in the early 1990s. Back then, prise Associates, a life sciences venture capital firm. There, he Rienhoff worked as a venture capitalist for New Enterprise combined his insights into clinical practice and a knack for Associates, whose offices overlooked the docks nearby. business with a vision for how the Internet could empower With her contemplative manner, punctuated by bursts of patients and improve health care. Along the way he forged enthusiasm, it’s easy to imagine Bea wrapping any adult— connections with physician-entrepreneur Seth Harrison and not least her father—around her little finger. What’s not so worked closely with James Clark, founder of Netscape and obvious on meeting this pint-sized yellow belt in kung fu is Healtheon (now WebMD). the role she and her father have played in promoting DNA- A voracious reader, Rienhoff steeped himself in issues based personalized medicine. related to intellectual property, clinical trials, and trends It would take a trained clinical geneticist—her father, relevant to the emerging biotech sector. It took him just a for example—to detect the subtle traits that suggest that few years to come across the technology that would anchor Bea’s slight frame and wide-set hazel eyes owe to a mutation his own first startup. among the genes that program some of the earliest steps in In 1998, he moved to California’s Bay Area to found DNA embryological development. Sciences, based on a high-throughput device to speed large- In his ongoing quest for a definitive diagnosis for his scale genomic sequencing in the lab. By recruiting volunteers daughter, Hugh Rienhoff has taken a page from each of the from around the world who would provide both medical careers he’s pursued since he earned his MD at Hopkins— histories and DNA samples, DNA Sciences sought to create incorporating a dash of do-it-yourself genetic diagnostics, a “gene trust” for use by scientists seeking the precursors a healthy dollop of Internet-based crowdsourcing, and the to disease, as well as pharmaceutical and other life sciences insights of a widely distributed team of academic experts. companies developing diagnostic tests and treatments based His approach has garnered criticism as well as praise, and on the genome. there have been plenty of dead-ends. The $3 billion Human Genome Project had passed its But Rienhoff is circling ever closer to insights about the midpoint that year and the promise of personalized medi- biology behind Bea’s low muscle mass and the resulting cine—the notion that both prevention and cure could be weakness and fatigue—information he hopes will provide tailored to a person’s unique genetic predispositions—had clues to how her condition will play out over time. become something of a holy grail. Funded by Harrison’s ven- ture capital fund, DNA Sciences boasted an all-star board of Building a Gene Trust directors including Netscape’s Clark and James Watson (with Bea was born in December 2003, a few months after her Crick, of double-helix fame). “The knowledge we gain from father’s 51st birthday. Yet even before she left the delivery the gene trust has the potential to change medicine forever,” room, the pediatrician flagged some subtle indicators of the company’s site promised in 2000. “But we can’t do it genetic trouble: Bea had a port-wine stain on her face (since without your help.” faded), poor muscle tone, disproportionately long feet, and It was a grand vision. By that time the company had tightly clenched fingers and toes. The constellation looked a raised more than $100 million and grown to nearly 200 em- lot like Marfan syndrome. ployees. But when the dot-com bubble burst in 2001, DNA If anyone was equipped to make sense of Bea’s symptoms, Sciences’ bottom line went with it. The day before the twin it was her father, by then a Silicon Valley-based biotech towers fell in Manhattan, the board announced a lay-off of entrepreneur and venture capitalist at the leading edge of the half the firm’s employees; Rienhoff stepped down as CEO. move toward consumer-oriented genomic sequencing. Three years later, the company filed for Chapter 11. “The tech As a fellow in clinical genetics at Hopkins in the late wreck happened right as we were going public,” says Harri- 1980s, Rienhoff had trained at the elbow of the legend- son. “It was literally a plane crash.” ary Victor McCusick ’46, founder of Hopkins’ Division of Rienhoff retrenched, investing in other biotech startups, Genetic Medicine and an early expert on the molecular serving on the boards of directors for a handful of them,

32 • Hopkins Medicine • Fall 2012 and tending his growing family with wife, Lisa Hane. Son of vascular disease. A subsequent genetic test confirmed that Colston was born in 1998 and MacCallum in 2001. In the the Loeys-Dietz diagnosis didn’t fit either. delivery room with Hane and their new daughter in 2003, Rienhoff breathed a sigh of relief, but he was far from sat- Rienhoff was all father and husband. Back home, though, his isfied—plagued, he recalls, “by the unanswered question” of clinical training spurred him up the stairs to his attic office, whether Bea was at increased risk for the ticking time bomb where he devoured his former mentor’s papers on Marfan. of vascular disease. Bea was 10 days old when an orthopedist suggested that she had Beals, also associated with mutations in the TGF-ß pathway. Rienhoff did his reading, then sent Bea’s records to The Bea Project is Born Rodney Beals himself, an orthopedist in Oregon. Not a fit. How do you mark the launch of a quest? Is it the first time By the time Bea was five months old, her symptoms were the vision is spoken aloud? The bottle, smashed against the more alarming: She still had poor muscle tone and while her hull of a ship when the craft is christened? limbs were all growing at a healthy clip, she wasn’t gain- For Rienhoff, the journey to understand Bea’s biology ing weight. “For a mother, the most important thing is that happened in stages. By the time Loeys-Dietz was off the you’re feeding your child, that she’s getting enough to eat,” table, Rienhoff knew that uncovering Bea’s diagnosis would says Hane. The two undertook an evaluative 36-hour inpa- require more than just literature reviews, clinical exams, and tient hospitalization to determine whether Bea would need consultations with experts. Someone was going to have to supplementation with a feeding tube. “At the end of it,” says analyze each of the genes implicated in Bea’s TGF-ß path- Hane, “they concluded that she was feeding properly, she was way, looking for the unique mutation at the heart of her getting nutrition, she just wasn’t growing at the normal rate.” symptoms, including the one most complicating her life—an Specialist after specialist examined the infant, offering inexplicable dearth of muscle growth. up a potpourri of diagnoses: amyoplasia congenital, cystic What happened next has made Rienhoff a minor celebrity fibrosis, metabolic syndromes, a mitochondrial defect. Rien- in the do-it-yourself biology world and a lightning rod in the hoff dived even deeper into his reading, putting out the word debate over personal genomics. Rienhoff launched “The Bea among friends and former colleagues on both coasts, seeking Project” by contacting scientists investigating the TGF-ß referrals to someone expert enough to name his daughter’s condition. When Bea started standing, another “I’m not content to wait for a paradigm shift,” says clue emerged. She had to use her arms, Rienhoff. “I want to be responsible for one.” bracing them against her legs for extra leverage, to push herself erect. Rien- hoff recognized the tactic as a classic indicator of Duchenne’s muscular dystrophy, a fatal condition caused by a recessive gene. “I needed a comprehen- sive, old-fashioned assessment of her symptoms,” says Rienhoff, who called his former colleagues in Baltimore. “I needed to come back home—Hopkins is really grounded in the clinical arts and that’s really the big message of my Hopkins education: Lay your hands on, get a good history, and most of the time you’ll get the diagnosis.” In March 2005, Bea had a comprehensive exam with a team of pediatric clini- cal geneticists at Hopkins’ Institute of Genetic Medicine. They suggested a particularly terrifying TGF-ß anoma- ly—now known as Loeys-Dietz for the two Hopkins professors who described it in a January 2005 Nature Genetics article. People with the mutation de- velop such profound aortic warps and arterial convolutions that they rarely live beyond their mid-20s. Bea underwent an echocardiogram just days after her return home. Rien- hoff watched the entire procedure like a hawk. As with each sonogram that Bea has had since, it showed no sign pathway to ask if they’d sequence that part of Bea’s genome. “There’s so much data and no good software to analyze Hopkins’ Se-Jin Lee, MD/PhD ’89, a professor of Molecu- it,” he says. “When you’re talking about 20 million [base lar Biology and Genetics and an expert in the TGF-ß gene pairs], you need a collaborator to look at it.” With that, responsible for curtailing muscle development, was among Rienhoff took the Bea Project public. Nature put a photo of many who declined to participate. Hugh and Bea on its cover. Wired and Discover ran stories. What Rienhoff was proposing was technically an experi- He penned a feature-length, do-it-yourself article for Make ment, Lee pointed out. For any academic scientist to touch magazine, and gave talks at Google, Cold Spring Harbor, so much as a hair on Bea’s head—let alone start sequencing and at UCLA, for a conference on “outlaw biology.” her genes—an institutional review board (IRB) would have “I’m definitely outside the establishment, whether it’s big to give its blessing. pharma, biotech, or academia,” he says. “I’m a gypsy and Rienhoff felt he didn’t have the time to wait for IRB I prefer that—there’s so much more freedom to work with approval, and back then, consumer-targeted whole genome different kinds of people in industry, academia, in different sequencing cost $350,000. Even more than cash, this dad companies.” had connections—to used equipment, to labs for hire, to Rienhoff also took to the Internet, launching MyDaugh- help and guidance from the cadre of experts, many of them tersDNA.com, intended as a forum for parents of children personal friends, with whom he’d been consulting. with undiagnosed congenital conditions and the clinical Rienhoff decided to sequence his daughter’s DNA him- geneticists who might be able to help. Ideally, he would find self. another Bea, and if nothing else, he could empower other He started with a visit to a phlebotomist—Rienhoff has parents like himself, looking for answers. never drawn Bea’s blood or performed any other medical Duke University’s Misha Angrist, who had his own DNA procedure on her, citing both the Hippocratic oath and his sequenced and published for the Personal Genome Project, duties as a father. Vial in hand, he went to the Stanford lab is author of Here Is a Human Being: At the Dawn of Personal of Nobel laureate Andy Fire, who provided access to tools for Genomics. In the book, he writes extensively about the intel- extracting Bea’s DNA. And then with a collection of used lectual property and privacy issues associated with genetic equipment purchased for less than $2,000 and installed in material, as well as Rienhoff’s work at DNA Sciences and on his basement, Rienhoff amplified the DNA in his daughter’s the Bea Project. white blood cells, harvesting enough genetic material from “Hugh knows what he doesn’t know, and he’s constantly the phlebotomist’s sample that a for-profit lab could sequence looking for advice and support and insight,” says Angrist. the strands associated with the TGF-ß pathway. “For him, it’s not an academic reputation or publishing When the results came back, Rienhoff copied the entire papers or getting grants or winning prizes. He wants to save sequence into a Microsoft Word file, then painstakingly his daughter’s life and that dwarfs every other consideration. reviewed each string of letters looking for diversions from the There really is no other consideration.” associated sequence published in the Human Genome Proj- Having failed to discover the explanation for Bea’s ect. With Lee’s guidance, Rienhoff started with receptors for symptoms by comparing her TGF-ß pathway to that of the myostatin, the gene to which Lee has devoted his research. Human Genome Project reference, Rienhoff turned to his When he found nothing there, he expanded his search to the longtime friend and colleague Jay Flatley, the CEO of Il- rest of Bea’s TGF-ß pathway. The work was slow and - lumina, a giant in the world of consumer, agricultural, and taking, a process he’s described as “hand-to-hand combat.” medical sequencing technology. In 2008, a team at Il- lumina sequenced all the expressed genes of Bea, her Mighty Mice brothers, and their parents. Rienhoff took the results to Among the cadre of scientists who’ve helped Hugh Rienhoff, Se-Jin Lee stands out. He his attic office, poring over has furnished vital insights into the molecular cascade responsible for cueing muscle growth. “He the files in search of variants thinks therapeutically about the TGF-ß pathway,” says Rienhoff. in Bea’s file. In late 2009, Molecular Endocrinology published Lee’s description of the first gene in the pathway’s superfamily he narrowed in on a likely in 1990; biochemical details of the other genes followed. To reveal what each TGF-ß gene actually candidate, the gene on Chro- does, Lee created a series of knockout mice, deleting one gene from each strain, then meticulously mosome 20 responsible for analyzing the resulting litters to discover how the genes he’d eliminated had influenced embryonic producing copine-1, a remote development. element of the TGF-ß signal- Most of the pups died, but one strain not only survived, they thrived. They had four times more ing cascade. With help from muscle mass, no body fat to spare, extraordinary strength, and excellent health. Lee dubbed the gene a Harvard scientist, he devel- responsible myostatin. Nature published the finding in 1997. Myostatin keeps our muscle growth in oped an assay to detect Bea’s check; without it, Lee’s brawny knockouts rippled with definition befitting a bodybuilder. copine-1 mutation in samples Now a professor in Hopkins’ Department of Molecular Biology and Genetics, Lee has since found from 400 anonymous donors. evidence of naturally occurring myostatin knockouts, including heavily muscled Belgian Blue and Pied- Forty of them shared the montese cattle and a super muscular German child. mutation. “Even though we Today, Lee investigates compounds that interrupt the TGF-ß pathway and block the effect of knew nothing about those myostatin to enhance muscle development. Bea and her family aren’t the only ones with a stake in 400 people, we knew it was what he finds—people with muscular dystrophy, cancer, AIDS, and even those of us feeling the ef- very unlikely that 1 percent fects of the aging process could all benefit from compounds that promote musculature. ST

34 • Hopkins Medicine • Fall 2012 “For Hugh, it’s not an academic reputation or publishing papers or getting grants or winning prizes. He wants to save his daughter’s life and that dwarfs every other consideration.” —Misha Angrist, Duke University of the population around the world would be like Bea,” says ness about her,” says Hane. “Instead of letting those physi- Rienhoff. “That told me we had to cast the net further—we cal distinctions get her down, she embraces them and takes had to start looking at the whole genome.” He went back to them as her own, a sort of take-it-or-leave-it approach.” the drawing board, getting Illumina to sequence the entire Now free of the looming terror of an aortic blowout for family’s genome. Bea, Rienhoff has turned his attention to understanding the Alan Beggs, PhD ’88, a professor of pediatrics at Harvard basic science of the TGF-ß pathway and its role in develop- and director of the Manton Center for Orphan Disease ment. To do so, he’s begun integrating insights gleaned Research at Boston Children’s Hospital, consults regularly from a half dozen scientists at Harvard, Hopkins, and other with Rienhoff on the genetic pathways associated with the academic medical centers. “I want to study TGF signaling in inherited muscle weaknesses he investigates. Beggs notes a whole animal,” he says. “There are multiple layers of regula- that while he works with hundreds of parents grappling with tion of the pathway.” “orphan diseases”—conditions so rare they attract minimal This fall, Rienhoff was submitting a case report about attention from scientists and pharmaceutical companies— Bea to a peer-reviewed journal. “You have to be persistent, Rienhoff is unique both in his scientific training and access systematic, scientific,” he says, “but if you just follow the cur- to resources. rent paradigms, you’re likely to have to wait for a paradigm While Beggs calls Rienhoff’s degree of involvement an shift. That’s the nature of science, but I’m not content to wait “extreme case,” he also believes the quest to understand Bea’s for a paradigm shift. I want to be responsible for one.” biology promises new insights into other facets of both mus- Already, the insights Rienhoff has gleaned from oversee- cle weakness and orphan diseases—the intellectual legacy of ing the Bea Project have infused his professional trajectory— Victor McKusick, who emphasized the insights to be gleaned and an emerging model in drug development—over the last from studying singular conditions. five years. Says Beggs, “[Bea] may have a mutation in a gene that’s In 2007, he launched Ferrokin BioSciences, a micro phar- of interest to a lot of people, and reveal things about muscle maceutical company that is testing a chelation drug to coun- that would be useful to people with many different condi- ter the iron toxicity that accompanies frequent transfusions. tions. Learning about her has the potential to inform us The company owes its distributed research and development about something much more common.” model to the experience Rienhoff has had working with Based on his latest research, Rienhoff now believes that TGF-ß experts around the country. Last spring, Dublin- the structural heart and circulatory defects that kill many based Shire acquired Ferrokin in a deal worth more than people with TGF-ß anomalies—including those with Loeys- $100 million. Shire retained Rienhoff and four other of the Dietz and Marfan—are less likely to afflict Bea. company’s employees, as well as a few of the 60 contractors “The biochemistry that we’ve done suggests a different who had designed and executed the Phase I and II clinical mechanism of disease.” More likely, he believes his daughter’s trials of Ferrokin’s compound. long-term health challenges will involve orthopedic issues: In addition to his new duties with Shire, Rienhoff contin- While her limbs are as long as those of any other child her ues his monthly pilgrimage to Harvard, where a Bea Project age, her scant muscles tire quickly. scientist has been analyzing the TGF-ß pathway’s influence on muscle development in embryonic . Meanwhile, Shifting the Paradigm a team in Arizona has begun development on a knockout This fall, Bea Rienhoff started third grade. Her favorite sub- mouse with a mutation to its TGF-ß pathway that mirrors ject is art, especially sculpture. At home, she helps with the the one in Bea’s genome. Eventually, Rienhoff hopes to learn dishes and takes turns feeding the family’s outsized rabbits. whether the “Bea mouse” develops vascular disease. Other than her specially crafted orthotics and regular occu- The mice and frogs are interesting, says Rienhoff, but in pational and physical therapy, she’s pretty much just like any the end his daughter isn’t her disease. “Bea defines herself— other kid, taking piano lessons and practicing her kung fu. and we all define her—in terms of what she can do and who “There are some physical things she’s not strong enough she is,” he says, “not what she has.” to do,” says her mother, “but I’ve always tried to deal with “She has so many adaptations that allow her to be her like I have with the boys. Bea has certain motor deficits herself,” says her father. Over the summer, while her older still, but it’s just a daily part of our lives.” More powerful is brother rehearsed for his part as Frederich in The Sound of the girl’s fearlessness and an independent streak. When the Music, Bea banged out the tune to “Somewhere Over the family was traveling in Ecuador this summer, Bea found a Rainbow” for her father on the family piano. “It’s poi- kid-sized tuxedo, as well as a perfectly fitted black fedora, gnant,” Rienhoff admits, “but we’re out of the acute phase trimmed with a peacock feather. She wore the combo for and dealing with something chronic now—our relationship much of the remainder of the trip. “When her classmates see is based on admiration.” her and interact with her they recognize a physical unique- *

Hopkins Medicine • Fall 2012 • 35 Class notes

1954 Gene Blank, of Portland, Ore., has The Success published USMC 457703, his memoir of Failure of combat in the Pacific during World War II. For Chuck Tuchinda, new products mean big business. Herbert Fred, of Houston, Texas, professor of internal medicine at the Uni- In a 20-month period between 2006 and versity of Texas Health Science Center, 2008, Charles (Chuck) Tuchinda ’01 presented the Special Dean's Lecture at oversaw the introduction of three new The University of Texas Medical School medical information technology products, at Houston. earning his then employer $25 million in new business. But Tuchinda insists his method for 1956 success “is all about failure.” Tuchinda cut his (tech) teeth David Paton , of East Hampton, N.Y., “It’s all about experimenting and failing at Hopkins with PagerBox. has received the 2012 Sixth Form Leader- early,” explains Tuchinda, 37, now chief in- ship Award from The Hill School, the novation officer for the health care arm of Hearst Business Media and VP 161-year-old prep school from which he for innovation at two of its subsidiaries, Zynx Health and First Databank. graduated in 1948. Paton, a member of “Rather than try to be a fortune teller, saying, this definitely will be the thing the Wilmer Eye Institute faculty from that works, I test several ideas by prototyping them, get feedback, and then 1964 to 1970 and also dean of admis- make a more informed decision about which to pursue. sions for the School of Medicine for four “I launched two products last year and I probably had 18 other projects years, is past chairman of the American fail, to get a yield of two,” he adds. Yet those two products already have Board of Ophthalmology. He also is the earned Hearst more than $1 million in new business. founder and former medical director of One of them is AlertSpace. It is designed to improve the alert system in Project ORBIS International, the world’s many electronic medical record programs, which can bombard physicians only flying eye hospital. and cause “alert fatigue.” “We wanted to build a system that would work with the major EMRs and cut out the ‘noise’ so that each message had some 1959 meaning to it,” he says. AlertSpace went from the drawing board to clients Robert Ruben , of Bronx, N.Y., is chair in about six months, which is “relatively fast for this industry,” he says. of the Section on the History of Medi- Tuchinda’s interest in medical software started at Hopkins when his re- cine and Public Health at the New York search project, overseen by pediatric cardiologist W. Reid Thompson Academy of Medicine. (Fellow, HS, 1984-87), led to development of a heart sounds database. At Hopkins he also invented PagerBox, an online system that sends text 1962 messages directly to alphanumeric pagers, cellphones, and other devices John Cameron , of Baltimore, Alfred and keeps patient information flowing to the internal faculty and staff. He Blalock Distinguished Service Professor and oncology researcher Luis Diaz (HS, 1998-2001; fellow, 2001-04, of Surgery in the School of Medicine, faculty, 2004-07) worked together to ensure that PagerBox re-engi- was the first visiting professor and leader neered the process of inpatient health care practice. of the California-based Sansum Clinic’s After completing his internship and residency at Hopkins, Tuchinda Surgical Academic Week. earned an MBA at Harvard in 2006 and then quickly assumed three vice presidencies—for business development and product strategy, acute care 1963 solutions, and content solutions—at San Jose, Calif.-based Eclipsys Corp., S. Robert Lathan Jr. , of Atlanta, Ga., a health care IT solutions vendor later acquired by Allscripts. He assumed has published a book about his grand- the Hearst Business Media jobs, with offices in San Francisco and Los Ange- father: Grand Old Man, Life of Samuel les, in 2010. Boston Lathan—the last surviving Con- Tuchinda and his wife, pediatrician Lynn Peng ’01, have two daughters, federate veteran of Chester, S.C. “Sadly, Alexis, 6, and Natalie, 4. He says it’s too early to tell if they will enter the I was only one year old when my grand- family business of medicine. “One of my daughters has said she wants to be a father died at age 96,” notes Lathan, who doctor … but she also said she wants to be a Power Ranger.” Neil A. Grauer

36 • Hopkins Medicine • Fall 2012 | Class Notes |

previously published The History Pushing the Limits of South Carolina, a collection of the writings of his great uncle, the Hildreth honored for his influence in combating HIV. Reverend Robert Lathan. Raised in the small southern Arkansas city of Camden, James E. K. 1966 Hildreth ’87 recalls his mother telling him, “Your circumstance does not Thomas Vander Salm, of Salem, limit your possibilities.” Mass., chief of cardiac surgery at “James has lived by that motto to become one of the most influential HIV North Shore Medical Center Heart doctors in the world,” said Dean/CEO Edward Miller, who recently re- Center and clinical professor of tired. “He is a model alumnus.” Hildreth was named to the Society of Scholars surgery at Harvard Medical School, in April and received a 2012 Alumni Association Knowledge for the World has been named the 2012 Com- Award in May. Both honors recognize his extraordinary achievements as an munity Clinician of the Year by his internationally renowned AIDS researcher, mentor to other medical scientists, physician peers of the Essex South and academician. District Medical Society. Today, as dean of the University of California, Davis, College of Biological Sciences, Hildreth oversees 125 faculty, 5,312 undergraduates, and 455 graduate 1967 students, and manages a $90 million budget, which includes nearly $60 mil- Richard Bransford, of Kijabe, lion for research. He particularly enjoys introducing undergraduates to the lab. Kenya, has received the American “Almost every year, I invite a few undergraduates to work in my lab. [They] ask College of Surgeons’ 2012 Surgical the questions no one else thinks to ask, and sometimes they come up with the Humanitarian Award in recogni- answers no one else has thought of,” he says. tion of his more than three decades A 1979 graduate of Harvard, Hildreth became the first African-American of service in Africa, primarily in Rhodes Scholar from Arkansas. After earning a PhD in immunology from the African Inland Church (AIC) Oxford in 1982, he began medical school at Hopkins. He joined the faculty upon Kijabe Hospital. In 2004, he co- graduation and rose steadily in the ranks, becoming the first African-American founded a 67-bed facility, Beth- in Hopkins history to earn a full professorship with tenure in the basic sciences, anyKids at Kijabe Hospital, which in 2002. From 1994 to 2001, Hildreth also served as the first associate dean has become known widely in Africa for graduate student affairs. While in that job, he created a summer research as a referral center for disabled chil- program for underrepresented minorities and actively recruited undergraduate dren and is supported by a network students to graduate programs. of 14 outreach clinics across Kenya. Hildreth’s research on AIDS, begun in 1986, has resulted in more than 80 scientific articles and seven patents. One protein he discovered while at Oxford 1969 is the basis for an FDA-approved drug, Raptiva, used to treat psoriasis. Richard Bensinger, of Seattle, During a seven-month stint in 2001 as chief of the NIH’s Division of Re- Wash., recently finished a one-year search in the National Center on Minority Health and Health Disparities, Hil- term as president of King County dreth and his research team discovered that cholesterol is active in HIV’s ability Medical Society. to penetrate cells, and that removing the fatty material from a cell’s membrane can block infection. With that knowledge, Hildreth’s team then developed an 1973 odorless, undetectable contraceptive vaginal cream that destroys the AIDS Mark Rockoff, of Hingham, virus and holds the promise of stopping the disease’s transmission. NAG Mass., has been elected to a one-year term as president of the American Board of Anesthesiol- ogy. He is also vice-chairman of the Department of Anesthesiology, Perioperative and Pain Medicine at Children’s Hospital Boston and professor of anesthesia at Harvard Medical School. 1974 Lawrence Wasser, of Louisville, Ky., is director of the Newborn Nursery at the University of Louis- ville Hospital and on the faculty of the Louisville School of Medicine Hildreth helped develop a contraceptive cream that destroys the AIDS virus. in general pediatrics.

Hopkins Medicine • Fall 2012 • 37 | Class Notes |

1975 Shelby Wilkes, of Atlanta, Ga., was chosen as the 2012 Male Alum- nus of the Year for America's Histori- cally Black Colleges and Universities. Wilkes is a vitreoretinal surgeon who specializes in treating diseases of the retina and vitreous humor, including diabetic retinopathy. James, also an art collector, describes decoys as “floating 1977 folk sculpture.’ Kenneth Laws, of Nashville, Tenn., has joined the five-hospital Saint Thomas Health system as a cardio- thoracic surgeon and has helped to establish a new practice, Heart, Lung & Vascular Surgery. 1978 Decoy Diagnostician Kenneth Tyler, of Denver, Colo., James uses X-rays to spot “fake” waterfowl imposters. was elected as a 2012 Academy Fel- low of the American Academy for A. Everette James Jr. got his first taste of waterfowl hunting on Mary- Microbiology. land’s Eastern Shore in the early 1970s, when he was an associate professor and director of the School of Medicine’s radiological research laboratories. He was 1981 enchanted by the decoys that are used to lure live birds within shooting range. Scott Lippman, formerly of “They looked like floating folk sculpture to me,” recalls James, who went on Houston, Texas, was named director to become head of radiology at Vanderbilt from 1975 to 1992 and founder of its of Moores Cancer Center at Univer- Center for Medical Imaging Research. “When I found out that they used these sity of California, San Diego. He is beautiful objects to throw in the water and hunt; and people abused them, nationally known for his molecular broke them and burned them; let them float away; stole them. I mean, the attri- studies aimed at determining cancer tion rate.” risk and at developing methods for Indeed, it is precisely that attrition in wooden waterfowl decoys—the finest personalized treatment and preven- of which were hand-carved and painted between the late 19th century and mid- tion of cancer. dle 20th century—that has made them so prized by connoisseurs of American folk art. (To date, the highest auction price for a decoy has been the $856,000 1983 fetched in 2007 for a red-breasted merganser hen, carved by Lothrop Holmes.) W. P. Andrew Lee, of Baltimore, While at Hopkins, James began collecting decoys and foresaw the likelihood professor and director of Hopkins’ that fakes were bound to flood the marketplace. His solution? Use radiography Department of Plastic and Re- as a noninvasive, sensitive method for documenting a decoy’s condition, age, constructive Surgery, was recently and authenticity. Beginning his X-raying of decoys at Hopkins, he continued the elected as chair of the American practice at Vanderbilt. Board of Plastic Surgery, Inc. James has used Sherlockian precision to determine the significant things to look for in decoy X-rays: invisible fractures or hairline cracks; the extent and 1984 distribution of old paint; the age, condition, and placement technique used for Joseph Marotta, of Troy, N.Y., such “internal hardware” as the nails used to affix the decoy’s head and neck to has established Medicus in Christi, the body and the weights for steadying it upright in the water. Ltd., a non-profit organization that The X-rays even can determine if fabricators have used intentionally rusted provides medical care, equipment, nails to make bogus decoys look old, he notes, since “the rust will be located at and training to impoverished peoples the entry as it will have been sheared from the surface of the nail when it was in the developing world. Marotta has positioned.” A well-known decoy-maker’s use of nails also can be as distinctive as also established an orthopedic center a signature, he adds. in Ghana, West Africa. Now 74, James doesn’t X-ray that many decoys these days but is happy to re- view and analyze X-rays sent to him by others. His own collection of decoys has 1985 dwindled since he and his wife, Nancy Jane Farmer, began donating their exten- Ralph Hruban, of Baltimore, sive collection of folk art—including paintings, quilts, and pottery—to museums, professor of pathology and oncol- among them the St. James Place Museum that they created by restoring a 1910 ogy in the School of Medicine, has Baptist church in his hometown of Robersonville, North Carolina. NAG

38 • Hopkins Medicine • Fall 2012

| Class Notes | Faculty, Fellows, House Staff begun posting a series of “Osler Minutes” on the Department of Pathology’s website: http:// Neil (Tony) Holtzman (HS, pe- Cancer Center. He is rated one pathology.jhu.edu/department/ diatrics, 1959-62; faculty, pediatrics, of U.S. World News & Report’s about/history/osler-minutes.cfm. 1964-2002), of Menlo Park, Calif., Top Doctors. has published The Railroad, the sec- Charles Sawyers of New ond in his “Adirondack Trilogy” of Kathryn Gardner (faculty, ra- York, N.Y., is president-elect of novels. The first novel in the trilogy, diology, 1991-92), of New Albany, the 34,000-member American Axton Landing, was published in Ohio, has been inducted as a Association for Cancer Research. 2011. The third novel, Forever Wild, fellow in the American College of Sawyers is chair of the Human will be published in 2013. Radiology. Gardner is currently Oncology and Pathogenesis Pro- vice president of Radiology, Inc., gram at Memorial Sloan-Ketter- Ashok Kumar (faculty, radiology, medical director of Mt. Carmel ing Cancer Center and a How- 1974-91), of Houston, Texas, is West Women’s Health Center, ard Hughes Medical Institute chief of at the and a radiologist with the Mount investigator. He also is a professor University of Texas MD Anderson Carmel Health System. in the cell and developmental biology program in the Depart- ment of Medicine at Cornell’s Weill School of Medicine. Society of Scholars 1987 Ten alumni, former house staff, fellows, and faculty were inducted into the So- Carolyn Cidis Meltzer, of ciety of Scholars last spring. Created in 1967, the society honors those who have Decatur, Ga., William P. Tim- gained distinction since leaving Hopkins in physical, biological, medical, social, mie Professor and Chair of or engineering sciences. The latest inductees are: Radiology and Imaging Sciences and associate dean of research • T imothy Buchman (HS, surgery, 1980-85), founding director of Emory at Emory University’s School of University’s Center for Critical Care Medicine, was honored for her • James E.K. Hildreth ’87 (fellow, pharmacology and experimental therapeu- accomplishments at Emory’s tics, 1983-84; faculty, pharmacology and molecular sciences, pathology, im- Second Annual Women’s History munology and infectious diseases, 1987-2005), dean of the College of Biologi- Month program. Meltzer led the cal Sciences, University of California, Davis clinical evaluation of the world’s first PET/CT scanner. • Christoph Lengauer (fellow, oncology, 1994-96; faculty, 1996-2005), chief scientific officer, Blueprint Medicines 1995 • V incent Manganiello ’67 (HS, pediatrics, 1967-68), chief of the Laboratory Jeffrey Wiese, of New Orleans, of Biochemical in the Cardiovascular and Pulmonary Branch of La., has been elected to the Board the National Heart, Lung and Blood Institute of Regents of the American • Teri Manolio (fellow, general internal medicine, 1984-87), director of the Office College of Physicians. He is a of Population Genomics at the National Human Genome Research Institute professor of medicine and as- sociate dean of graduate medical • Stephen McPhee ’76 (HS; fellow, medicine, 1976-80), professor emeritus of education at Tulane University. medicine at the University of California, San Francisco • John A. Phillips III (fellow, pediatric genetics, 1975-77; faculty, pediatrics, 2000 1977-84), head of the Division of Pediatric Genetics at Vanderbilt University’s Jennifer Arnold, of Houston, School of Medicine Texas, one of the stars of the popular TV program The Little • Robert Schleimer (fellow, allergy and clinical immunology, 1979-81; faculty, Couple, was the keynote speaker medicine, 1981-2004), chief of the Division of Allergy-Immunology; profes- at the University of Texas Medi- sor of medicine and otolaryngology—head and neck surgery, Northwestern cal Branch School of Medicine University’s Feinberg School of Medicine commencement ceremony. • Arjun Srinivasan (HS; fellow, medicine, 1996-2001; faculty, medicine, Arnold is medical director of the 2001-2008), associate director for Healthcare Associated Infection Prevention Pediatric Simulation Center at Programs, Centers for Disease Control and Prevention Texas Children’s Hospital and • S teven Wesselingh (fellow; faculty, neurology, 1991-94), executive director assistant professor of pediatrics at of the South Australian Health and Medical Research Institute Baylor College of Medicine.

Hopkins Medicine • Fall 2012 • 39

IN memoriam

School of Medicine

H. Fred Helmholz ’37, of Roches- ter, Minn., acclaimed for develop- ing respiratory care as a specialty, died on Jan. 7, very shortly after his 100th birthday. At the Mayo Clinic, he performed some of the first pulmonary function tests, and helped launch a school for respira- tory therapy. He was also a founder of the American Association of Respiratory Care. Michael DiMaio ’39, whose 35-year, Making Waves award-winning career as an inter- nist in private practice and at the Niedermeyer wrote the bible on electroencephalography. Rhode Island Hospital in Providence included nearly a quarter century as Ernst F.L. Niedermeyer, acknowledged worldwide as the foremost ex- head of the medical review board pert in electroencephalography and its diagnostic value, died of colon cancer that licenses physicians to practice in on April 5 at the age of 92. the state, died on Jan. 24. He was 99. Niedermeyer was a master of the clinical interpretations of electro- encephalograms (EEGs), recordings of the electrical activity in the brain; Bettina Meyerhof Emerson, Feb. co-editor of his specialty’s longstanding “bible,” Electroencephalography—Basic ’43, who spent most of her career Principles, Clinical Applications and Related Fields, now known as Niedermeyer’s caring for low-income families Electroencephalography; and director of Hopkins’ electroencephalography and children with developmental laboratory from 1965 to 1990. problems, died at her Seattle, Wash. Born in Germany, he moved with his family to Vienna when he was a teen- home on Oct. 18, 2011. She was 93. ager. He was inducted into the German Army after high school, and began Loring W. Pratt, Nov. ’43, of Fair- his medical studies even as World War II got under way. He was pulled from field, Maine, a nationally recognized school and sent to join a Panzer division on the Russian front, however, when expert on the treatment of chainsaw it was discovered that his maternal grandfather had been Jewish. Niedermeyer injuries to the head and neck, and a survived the horrendous battlefield winter of 1943-44, later telling a friend that former president of several national he and his fellow soldiers didn’t care about the Army’s mission or Nazism, they otolaryngology—head and neck sur- just wanted to find enough to eat and avoid capture by the Russians. gery organizations, died on March Wounded twice, he eventually was captured by American forces in 1944 13 at the Maine General Hospital in and then put on a U.S. troop ship full of wounded soldiers bound for home. Augusta. He was 93. He helped treat them, then was sent to prisoner-of-war camps in the Mid- Karl Emil Hofammann Jr., ’46, west and West. He returned to Austria after the war and earned his medical a Birmingham, Ala., gynecologist, degree at Leopold-Franz University in Innsbruck, where he ultimately would female urologist, and surgeon who become acting chief of the department of Neurology and Psychiatry. served as chairman of the Depart- When his hospital obtained an encephalograph under the postwar Mar- ment of Obstetrics and Gynecology shall Plan, Niedermeyer had to learn how to use it after the technician who at Birmingham’s Baptist Medical operated it was transferred. He quickly mastered the device, began applying Center for two decades, died on Jan. its recordings of brain waves to his growing interest in , and soon be- 15. He was 90. came instrumental in making electroencephalography a significant diagnostic and research tool. Charles W. Tillett ’46, of Char- Niedermeyer moved to the University of Iowa in 1960 and in 1965 to Hop- lotte, N.C., who developed the kins, where he was named electroencephalographer-in-chief. By the time he revolutionary corneal transplant retired in 1997, he had become “the most famous electroencephalographer procedure now known as DSEK in in the world,” says neurologist and neurosurgeon Ronald Lesser, who suc- 1954—more than 40 years before its ceeded Niedermeyer as head of the EEG lab. “He frequently was invited to “discovery” by others was herald- lecture in other countries, and influenced the interpretation of EEG around ed—died on Oct. 19, 2011. He was the world,” Lesser says. 91. He headed the Tillett Eye Clinic An avid hiker and mountain climber, Niedermeyer also was an excellent in Charlotte from 1954 to 1987. classical pianist. Neil A. Grauer

40 • Hopkins Medicine • Fall 2012

| Obituaries |

Lay M. Fox ’47, of Austin, Tex., a veter- clinic for low-income families, and He was known to long-time col- an Navy captain who served as Lyndon later director of the Department of leagues at the Providence Portland B. Johnson’s cardiologist during LBJ’s Health Services for the Association Medical Center as “Professor PK,” presidency, died on April 23. He was of American Medical Colleges. a remarkably skillful pathologist, 87. Following his retirement from the Andrew M. Nemeth ’53, of Wyn- diagnostician, and indefatigable Navy after a 21-year career, Fox served newood, Pa., died on Feb. 7 at the worker with a gentle wit. as medical director of D.C. General age of 84. A professor emeritus of Dennis Stevens Barlow ’85, of Hospital; director of the heart station at and a lecturer in psychiatry Eastford, Conn., died at his home Hospital; and at the University of , on January 20. He was 52. Follow- worked in Georgetown’s cardiology and he served on the faculty there for 40 ing internship and residency train- nuclear cardiology divisions until his years. He also maintained a private ing at the Macha Hospital in Zam- retirement in 1997. psychiatry practice for many years. bia, Africa, and the University of William L. Stewart ’51, a pioneer in James A. Schoettler ’57, of Chevy Vermont, he worked at the Mtsha- establishing the family practice of medi- Chase, Md., who practiced psychia- bezi Mission Hospital in Zimbabwe cine as a specialty, died on Nov. 18, 2011 try in the Washington, D.C. area for for five years. He returned to Con- in Highlands Ranch, Colo. He was 86. more than 40 years, died of bladder necticut in 1994 and worked as an James I. Hudson Jr. ’52, of Nashville, cancer on March 6 at his home. He emergency department physician at Tenn., died on April 27 at the age of 84. was 80. Manchester Memorial Hospital in He was the founder and first director Manchester, Conn., and Rockville Paul W. Kohnen ’65, of Portland, General Hospital in Vernon, Conn., of Hopkins Hospital’s Comprehen- Ore., died on May 7 at the age of 73. sive Child Care Program, a pediatric for the remainder of his career.

Pioneer in Pulmonary Medicine Permutt remembered for his warmth and wisdom.

Acclaimed physiologist Solbert (Sol) Permutt, a key figure in mained on the faculty for the creation and expansion of the School of Medicine’s Division nearly a half century. He of Pulmonary and Critical Care Medicine and a beloved mentor became a professor of to generations of physicians specializing in those fields, died on medicine and environ- May 23 of esophageal cancer. He was 87. sciences “It’s not possible to adequately describe the extent to which in the School of Public Sol’s curiosity, vision, and commitment drove not only the Health in 1965 and a creation of our division but, to a significant extent, the creation professor of medicine in of pulmonary medicine as a discipline,” said Landon S. King, the School of Medicine in professor of medicine, Hopkins’ vice dean for research and chief 1972. He retired in 2006. of pulmonary and critical care medicine. From 1972 to 1981, “He was the smartest physiologist and one of the wisest men Permutt was director of I will ever meet,” said physiologist Charles Wiener, professor the Respiratory Division of medicine, vice director of the Department of Medicine, and in Hopkins’ Department of Medicine, assuming leadership Dean/CEO of Perdana University Graduate School of Medicine. of both the clinical and research programs. He inaugurated Wiener, who came to Hopkins as a fellow in 1985, said he a collaborative program integrating the clinical, research, and quickly found Permutt to be an extraordinary mentor. “He educational activities of the division with programs in the always had time for young people and loved sharing his experi- School of Public Health. He also oversaw extensive growth in ence, wisdom, and excitement for medicine, scholarship, and the division’s clinical program, including the opening of a new education,” said Wiener. intensive care unit and a new bronchoscopy program, as well Born in Birmingham, Permutt earned his MD from the Uni- as of clinical consultative and inpatient services provided to versity of Southern California and came to Hopkins as a fellow in other Baltimore-area hospitals. medicine and environmental medicine in 1956. Two years later, he More than six feet tall, Permutt was known for his seem- became chief of the Division of Cardiopulmonary Physiology at ingly boundless energy—riding a bicycle from his North the National Jewish Hospital in Denver. He returned to Hopkins Baltimore home to Hopkins Hospital well into his 70s—as well in 1961 as an associate professor of environmental medicine at as his signature, large bow ties, which he began wearing as a what now is the Bloomberg School of Public Health and re- teenager. NAG

Hopkins Medicine • Fall 2012 • 41 | Obituaries | Former Faculty, House Staff Neuroanatomist Nonpareil As scientist and mentor, Molliver was a “mensch.” Curtis Prout (HS, internal medi- cine, 1942-43), of Manchester-by-the- Nearly every year from 1974 to 1994, Sea, Mass., a primary care physician and neurologist Mark for more than 65 years and a widely Molliver received one teaching known advocate for improving health award after another—making it hard care in prisons, died on December 2, to determine which of his accomplish- 2011, in his home. He was 96. ments had the most impact: his four William Henry Muller Jr. (HS, decades of classroom influence on un- surgery, 1944-49; instructor, sur- counted future or his gery, 1948-49), of Irvington, Va., landmark discoveries on the structure who launched the open-heart sur- of the brain and its response to drugs. gery program at the University of Molliver died on May 10 at Johns Virginia; developed the pulmonary Hopkins Hospital of complications fol- artery banding procedure for infants lowing cardiac arrest. He was 75. and children with certain kinds of His friend and colleague Solomon congenital heart disease; and oversaw Snyder, founder and long-time construction of a new University of director of what now is known as the Virginia hospital, died on April 19. He Solomon H. Snyder Department of was 92. , gives equal weight to both. “Mark was one of the coun- T. Franklin Williams (HS, medi- try’s greatest neuroanatomists,” says cine, 1950-53, part-time lecturer, Snyder, himself the discoverer of the geriatrics, 1983-89), former director of brain’s opiate receptors. He credits Molliver with making “major discoveries the National Institute on Aging, and about the role of serotonin,” the molecule in the brain most closely associated a pioneer in geriatric medicine, died with feelings of well-being and happiness. “For years and years he also was the of pneumonia at his home in Roches- premier teacher of for our medical students,” Snyder adds. ter, N.Y., on Nov. 25, the day before Neuroscientist David Linden, another former colleague of Molliver’s, his 90th birthday. agrees. “Mark was one of our very best teachers, extraordinarily gifted and John Anton Waldhausen (HS; clear,” says Linden. “What really stood out about Mark was his extreme colle- fellow, surgery, 1954-57), a protégé of giality and warmth, a gentle manner with everyone. He was scientifically critical surgeon Alfred Blalock and found- when called for but a real mensch and always willing to help people.” ing chairman of the Department of In addition to his discoveries about serotonin, Molliver uncovered the Surgery at Pennsylvania State Univer- adverse impact on the brain of the obesity drug Fen-Phen, which was among sity College of Medicine, of which he the factors prompting the FDA to ban it in 1997. His research also produced also became interim provost and dean, important findings about the drug MDMA, commonly known as “ecstasy.” His died on May 15. He was 82. Following research showed that both Fen-Phen and ecstasy caused brain neurons to die, his training under Blalock, Waldhau- leading to a reduction in serotonin levels. sen went to the University of Indiana Boston-born, Molliver received his undergraduate degree from Harvard Medical Center, where he developed in 1958 and his medical degree there in 1963. He came to Hopkins in 1965 as a the subclavian flap angioplasty that for postdoctoral fellow in neuroanatomy. He later held a second Hopkins post- many years was the standard treatment doctoral fellowship in neurophysiology under Vernon Mountcastle ’42, for coarctation of the aorta. It lowered often called the “father of neuroscience” for his discovery of the columnar the mortality rate of that disease from structure of the brain’s cells. nearly 60 percent to 3 percent. He In 1969, Molliver became one of the first residents in Hopkins’ then-just cre- then moved to the Children’s Hospital ated Department of Neurology. He joined the faculty as an assistant professor of Philadelphia, where at the request of anatomy and neurology in 1971, then rose through the academic ranks until of C. Everett Koop, he developed its he held full professorships in neuroscience and neurology. Although he retired congenital heart program. in 2006, he continued to come to work and attend departmental faculty meet- ings. Lonnie S. Burnett (HS, 1957-62; “Mark was tenacious and still passionate about research,” says Richard GYN/OB, fellow, microbiology, Huganir, director of the neuroscience department. “He still was collaborating 1962-64), a leader of Vanderbilt Uni- with other faculty members and coming to meetings until two weeks before versity’s OB/GYN department, died his death.” NAG on April 3 at the age of 84. While at

42 • Hopkins Medicine • Fall 2012 The School of Medicine also has received word of the following deaths:

Sheldon Fox ’4 2 Former Faculty, House Staff on Mar. 29, 2012 Justin J. Wolfson (fellow, radiology, R. Gordon Long (HS, , Virgil A. Place ’4 8 1949-50; HS, 1950-53) 1958-61; faculty, 1961-64) on Mar. 14, 2012 on May 2, 2012 on April 6, 2012 Sanford Chodosh ’52 John L. Pitts Jr. (fellow, pediatric Mamdouh M. Younes on Aug. 30, 2010 cardiology, 1953-55; assistant (fellow, gynecology/obstetrics, William Michael Holmes ’52 professor, pediatrics, early 1960s-89) 1958-59; HS, 1959-61) (Art as Applied to Medicine) on March 13, 2012 on Dec. 12, 2011 on April 4, 2012 Rosa Meysersburg Gryder Charles A. Stump Donald S. Daniel ’58 (fellow, ophthalmology, 1954-59) (HS, obstetrics, 1959) on Feb. 5, 2012 on Feb. 28, 2012 on Dec. 25, 2011 Lianne Krueger Sullivan ’99 Raymond Markley Jr. (part-time Onkar N. Sharma (fellow, (Art as Applied to Medicine) instructor in gynecology, 1954-1990) pediatric neonatology, 1969-70) on Jan. 10, 2012 on Mar. 4, 2012 on Feb. 10, 2012 James B. Brooks (HS, orthopedic Brent F.G. Treiger surgery, 1957; part-time assistant (fellow, urology, 1986-90; professor, 1958-2007) chief resident, 1990-91) on March 18, 2012 on Nov. 14, 2011

Hopkins, Burnett pioneered not only Joseph F. Kennedy (HS, gynecology/ ated affliction that causes significant in vitro fertilization procedures but obstetrics, 1965), whose pioneering re- rashes that develop into blisters on sex-change operations; at Vanderbilt, search on in vitro fertilization led to the women during and after pregnancy. he oversaw development of a leading first “test tube” baby born in San Diego, Luigi Giacometti (faculty, medicine, department in the field. died at his home in La Jolla, Calif., on 1981), of Potomac, Md., former chief of James Claris Wright Jr. (fellow, Jan. 24, following a four-year battle with the National Institutes of Health’s Cen- pediatric endocrinology and metabo- pancreatic cancer. He was 76. ter for Scientific Review, died on Oct. 9, lism, 1961-64), of Indianapolis, Ind., Thomas Provost (faculty, dermatol- 2011, of prostate cancer. He was 85. died on Mar. 22. He was 81. Indiana’s ogy, 1978-1996), former director of the Carol M. Meils (fellow, intervention- first pediatric endocrinologist, Wright Department of Dermatology, died on al cardiology, 1987-1991), of Milwau- served as director of the pediatric en- April 18, in Fairfax, Va., of pneumonia kee, Wis., died on April 1 following docrinology department at Indianapo- following a battle against colon cancer. an eight-year battle with breast lis’ Riley Hospital for Children and as He was 74. Widely respected not only cancer. She was 59. Meils was the first a professor of pediatrics at the Indiana in dermatology but internal medicine, female chief resident at Boston City University School of Medicine. rheumatology, and immunology, Pro- Hospital and Hopkins’ first female David L. Rimoin (HS, internal medi- vost often collaborated with rheuma- fellow in interventional cardiology. cine, 1963-64; fellow, genetics, 1965-67; tologists on research. Perhaps his major She founded her own cardiology prac- faculty, 1967-71), an acclaimed medi- contribution to the field was discover- tice and later developed the cardiovas- cal geneticist at Cedars-Sinai Medical ing the antibody marker that identified cular program at All Saints Hospital Center in Los Angeles, died on May an important subset of patients with in Racine, Wis. systemic lupus erythematosis (SLE), 27, just days after being diagnosed Zenobia Ann Casey (HS, anesthesi- with advanced pancreatic cancer. a mysterious autoimmune disease in which the body’s immune system mis- ology, 1999-2001; faculty, anesthesiol- He was 75. Rimoin conducted early ogy and critical care medicine, 2002- studies of dwarfism and other skeletal takenly attacks healthy tissue, leading to chronic inflammation of the skin, 2007), of Baltimore, died on Mar. 31. abnormalities while at Hopkins, and She was 47. She served as Director subsequently played a pivotal role in joints or internal organs. He also made important contributions to defining the of Adult Remote Anesthesia and was creating screening programs for Tay- a past coordinator of the Anesthe- Sachs disease. Such programs have immunological features of such blister- ing autoimmune diseases as gestational siology and Critical Care Medicine led to the virtual elimination of the residency lecture series. disease. pemphigoid, a rare, pregnancy-associ-

Hopkins Medicine • Fall 2012 • 43

| Alumni | Where A Gift Took Flight

ll it took was In the Armstrong a single look Building, on a wall in for Stephen the bustling student F. Wetherill, commons area, is a A&S ’68, Med ’71 , and his plaque dedicating the wife, Paula R. Wetherill, area to Jewel Hart to make their decision. In Coombe. “It’s a very 2008, the Wetherills had emotional experience traveled from their home for me to visit the in Wilmington, Delaware, Armstrong Building and for a “hard hat” tour of the see that plaque,” says Anne and Mike Armstrong Paula Wetherill. “It’s Medical Education kind of like visiting her. Building, then under And it’s so wonderful construction. Climbing the to witness the tangible steps in the main lobby to outcomes of this gift the second floor, the couple and to get to know our gazed up at the soaring scholarship recipients. I atrium and at the spacious Xuan “Tashin” Le-Nguyen ’12 (left) was the 2011-2012 recipient of feel like I’m now a part area surrounding them. a scholarship established by Paula and Stephen Wetherill to honor of Hopkins, like Steve.” “When we encountered Paula’s aunt, Jewel Hart Coombe. Her husband agrees. this wonderful space, Paula “When you’re given a and I instantly saw it as chance like I was, you a focal point for the student body,” relationship with the School of want to give back, especially to a great recalls Steve Wetherill. “The open Medicine, thanks to generous gifts institution like Hopkins,” he says. “This feeling of taking flight there was a to the School of Medicine Annual was the right gift at the right time for perfect match with the spirit of Paula’s Giving Scholarship Fund over the the right purpose—and named for the aunt. We knew we had the answer for years. A flurry of conversations and right person. We found the most fitting what we wanted to do.” visits ensued between the couple tribute for Jewel.” Paula’s aunt was Jewel Hart Coombe, and the school’s development staff, To learn more about the ways you a nurse who had spent her entire career culminating in that fateful visit to the can make a named gift to The Johns in the military, first in the U.S. Army new Armstrong Medical Education Hopkins University School of Medicine, Nurse Corps and later as a Major in the Building. “It was fortunate that we please contact the School of Medicine Air Force Reserve. During her years in had sufficient funds to underwrite Development and Alumni Relations the Army, Coombe had travelled around the atrium and to establish a named Office at 410-516-0776 or jhmalumni@ the globe on various posts, including a scholarship,” says Steve Wetherill. jhmi.edu. David Beaudouin stint on the front lines in Vietnam from “We gained the best of both worlds, 1966 to 1967 while serving with the 12th supporting medical students and the Evacuation Hospital. facility that houses technologically Stephen Wetherill Honored In her later years, Coombe, who advanced classrooms, a first-class gross had no children and whose husband anatomy lab, and open spaces for with ACP Award predeceased her, directed that most learning and collaboration.” of her estate be left to a charity of Xuan “Tashin” Le-Nguyen In recognition of his “abiding commit- her niece’s choice. “Although I was ’12, whose undergraduate studies at ment to excellence in medical care,” honored, I was at first overwhelmed by Yale focused on molecular, cellular, Stephen Wetherill recently was pre- the responsibility,” says Paula Wetherill, and developmental biology, was the sented with the 2012 Laureate Award who became the executor in 2007. “I 2011-12 recipient of the Jewel Hart from the Delaware Chapter of the wanted my aunt’s estate to go to one Coombe/Stephen F. and Paula R. American College of Physicians (ACP) organization where it could create the Wetherill Scholarship. “Receiving this at their Annual Scientific Meeting. In greatest impact, so we could say, ‘Look scholarship allowed me to concentrate honoring Wetherill, John H. O’Neill, at what we were able to do with my more fully on my studies and not have Jr., DO, FACP, Governor of the ACP aunt’s gift.’” While in the throes of to work part time, which can be a Delaware Chapter, noted, “Dr. Weth- settling the estate in California, Paula real challenge,” says Le-Nguyen, who erill is a long-standing and loyal sup- shared her concerns with her husband. foresees a career that includes teaching, porter of the College, has rendered His response was immediate, “Why not research, and a clinical practice in distinguished service to the Chapter, give it to Hopkins?” ophthalmology. “It has been a great and has upheld the high ideals and The suggestion made sense. The help—I can’t tell you how grateful I professional standards for which the Wetherills already had a philanthropic am for such a wonderful opportunity.” College is known.”

44 • Hopkins Medicine • Fall 2012 | Annals of Hopkins | The Dark, Looming Structure That Became Home So strong were the bonds that E. Hunter Wilson formed to Hopkins Hospital as a medical student that they remained unbroken throughout his long career.

By E. Hunter Wilson ’53

usk was just settling in each other for support. They volume of disease were at over Baltimore on Octo- were poorly dressed, small- their highest for study and ber 1, 1949, the evening ish in stature, and unsteady. treatment. I first viewed the Johns The man had a white blood- In those years, the Hopkins Hospital. An stained bandage wrapped hospital’s main entrance, hour earlier my two new over his head. The two of with its classic lobby and roommates, Bob Welch and Tom Lang- them had been praying dramatic 10-foot marble Dfitt, and I, had checked into our second- together in a church a few statue of Christ, was floor rooms in the row house at 726 blocks away, they told us, located on Broadway. A North Broadway. Fresh from college and when a gang of youths had linear wing running east feeling fortunate to have been accepted entered, struck him on the along Monument Street to Hopkins Medical School, we’d set head, snatched the woman’s E. Hunter Wilson housed semiprivate and around the time he out to explore the neighborhood. purse, and fled. Now, with entered medical indigent medical and sur- We found sustenance just down the a handkerchief over the school, in 1949. gical beds, the obstetrical street at a well-kept Greek restaurant man’s bleeding wound, they and gynecological wards, called Gounari’s. Then, continuing were looking for the hospital emergency classrooms, and outpatient clinics. By our stroll, we walked southward along room. We quickly searched it out for nature of its reputation, Hopkins had Broadway, crossing Monument Street. them and led them inside, where they attracted faculty of outstanding repute And there, taking up the east side of were promptly attended to. I remember and capabilities, each with a particular the whole next block, loomed the elon- thinking this was not a good omen for method of teaching and incidental ec- gated mass that was the hospital. the future. The scene was too much like centricities. I soon came to realize that None of us had seen this icon of Dickens to contemplate spending the it was the excellence of this faculty American medicine before, but in the next four years of my life here. that gave the hospital its honored place increasing darkness of evening, my own I smile now when I think back on in medicine. silent appraisal of its shaded Victorian that day 63 years ago. Little could I Our introductory lecture to anat­omy bulk and ragged red brick outline was conjure that my medical school experi- was given by Dr. Alan Graflin, one of one of disappointment and not a little ences would shape the rest of my life the most erudite speakers to face any apprehension. I suppose I had expected and that the elongated outline of the unsophisticated entering class. He let it a brighter and more modern place. This Johns Hopkins Hospital would become be known forthwith that he did not suf- dark, looming structure with its untidy for me a kind of mental mecca. Only fer slackers gladly. I still remember his silhouette did not seem to support its later would it dawn on me that the hos- declaration that “you will not be spoon- reputation. pital stood exactly where it belonged in fed at Hopkins. You’ll have guides but There were few people on the streets the city, at a place where it could do the they’ll just tell you where to dig. Only at that hour, I remember, but approach- most good for the people who needed it by digging hard will you learn—and ing us was an elderly couple leaning on the most, and where the proximity and remember to dig deeply! For God’s sake, be a doctor. Don’t be a jerk!” Another professor who remains “Only later would it dawn on me that the hospital unforgettable is the pathologist Dr. stood exactly where it belonged in the city, Arnold Rich. Although gravid, de- tached, and soft-spoken, he never raised at a place where it could do the most good his voice because he was used to having for the people who needed it.” the last word about any unsolved illness or death. Dr. Rich used the Socratic

PhotOS courtesy E. Hunter wilson Hopkins Medicine • Fall 2012 • 45 | Annals of Hopkins |

E. Hunter Wilson, last man on the right, with fellow residents in Medicine in the mid-1950s.

method of lecturing and it was un- and challenged him to let us prove could produce unfortunate results. On nerving to be called upon to stand and it. Standing in Dr. Welch’s room we one occasion, after a flowery introduc- answer a question such as “Dr. Her- placed the ether cone over his nose and tion purporting to portray one of the man, what is life?” In discussing why a mouth, and in about two minutes he distinguished and flashier surgeons, patient had died he always selected the collapsed unconscious on the floor. Be- the curtains parted and standing on most intricate cases. It was said of him cause of his size, we had great trouble stage in full form was the rear end of a that he could see past life into death moving him out to give him artificial donkey. We all found this enormously and vice versa. respiration. Fortunately, he was soon funny, but the professor himself, who Exchanges between Dr. Rich and on his feet, with his brain clearly un- took himself quite seriously, failed to our renowned professor of medicine harmed. Even today he is an associate see the humor. He bellowed, rose from Dr. A. McGehee Harvey as to the professor emeritus of ophthalmology at his seat in the front row and stormed nature and cause of death of undiag- Hopkins and a noted retinal specialist. out, never to return. nosed patients took place weekly at In our fourth year we were admit- None of this outrageous behavior the Clinical Pathological Conferences. ted to the wards, and after that, we could have happened, of course, without Looked upon as medical jousting almost never left the hospital. Under the familiarity and respect we developed events, these CPCs were famous the tutelage of a distinguished group of for our professors, many of whom were throughout the city and filled the Baltimore doctors who were well aware world famous for medical discoveries hospital lecture hall. For us they were of their status in holding admitting and innovations in treating disease. Day the high point of the medical week. privileges to Hopkins, we were now al- by day, along the bustling corridors of Dr. Harvey, of serious mien and a bit lowed to participate in caring for their the hospital, in its ORs, lecture halls, forbidding, seemed to know every- private patients. With three or four of and classrooms, we felt the uplifting thing. With his diagnostic acumen us assigned to each, these physicians energy and wisdom of those teachers. In and legendary of disease watched over our shoulders in daily the end, so strong were the ties I formed processes, he became for many of us a rounds as they showed us which clini- to the Johns Hopkins Hospital that they kind of metaphor for medicine itself. cal signs to look for in making proper remained unbroken until my retire- At length, our class of 75 stu- diagnoses and managing patients. We ment. During 40 years of practice as a dents—70 men, five women—began learned to draw blood and perform Baltimore internist, I myself became to feel like a family. Meanwhile, the daily physical exams, urinanalyses, one of those community physicians who hospital became some kind of home. EKGs, stool exams, and blood counts. looked over Hopkins medical students’ As we learned within this framework, And occasionally to our delight, we shoulders as they learned. To have been we also experienced some dramatic made unexpected diagnoses. Our days part of that family and this place for so moments. In our second year, when and nights were full. long was a gift. we had advanced to animal surgery And still we found time for humor. and anesthesiology, Dr. Robert Welch, The high point for revelry took place at E. Hunter Wilson practiced internal a towering figure, was so robust and the end of each year when the fraternity medicine in Baltimore for 40 years. He healthy he felt certain the inhalation of known as the Pithotomy Club staged has written two novels: In My Father’s ether couldn’t knock him out. To test an irreverent satire parodying faculty House (Johns Hopkins Press, 1989), and his theory, Tom Langfitt and I took foibles. This production of repartee and The Gemini Mutation(I. Universe an ether cone from animal surgery song got fairly raunchy at times and Press, 2008). *

46 • Hopkins Medicine • Fall 2012 | Learning Curve | A New Chapter After a decade of reflection, it’s time to move on.

BY DANIEL MUNOZ, MD ’04

This column was born about 10 seconds to traverse the Atlantic. Raj 2) to then reflect on their meaning. years ago. was enjoying his morning tea and bowl That process has evolved into an I was a second-year med student in of Frosted Flakes, all while perusing the essential aspect of my medical training the infancy of my clinical training. Still online news. His email inbox chimed. and (attempts at) maturation. on the classroom side of the mostly By the time I awoke, Raj’s reply was I am immeasurably indebted to mysterious world of patient care, I was already there. His feedback was (and the two editors for whom I have filled with equal allotments of wonder remains) memorable: Take out most of written, Edith Nichols and Sue De and naïveté about the chance to be the adverbs, go easy on the metaphors, Pasquale. They both established new a bedside doctor. And, like many of toss out the passive verbs, and then dictionary definitions of patience, my student colleagues, I embraced submit this for publication somewhere. all while I routinely redefined the any opportunity to witness medicine My first column in this magazine concept of the “deadline.” And they firsthand, no matter how peripheral (or was that account. each did something considerably more frankly, irrelevant) my involvement. valuable. They provided me with a The reality is that after years of blank canvas. They never assigned a lectures, homework, standardized specific topic. I have felt a freedom tests, and final exams in windowless that has been motivating and, at classrooms, the thirst for genuine times, thoroughly confusing. Their clinical experiences is, at a very basic only mandate was both simple and level, a thirst for some version of implicit: Make sure you write more humanity. Virtually any dose will from your heart than from your do. On a wintry afternoon during brain. When at times my brain that second year of medical school, exerted more keystroke control my classmate Brian and I ingested a than my heart, both had their ways powerful dose, when we witnessed a of offering criticism in seemingly patient die in the intensive care unit. complimentary fashion. So, shortly after 11 pm that night Ten years and a few dozen in 2002, from the kitchen table in columns later, I now close the my Charles Village apartment, I chapter on this space, grateful for sat down and crafted an email to I have considerably more a medium through which to share my buddy in London. Email was still gray hair and an ounce my training experiences and humbled this magical new medium, permitting or two more of wisdom— by the opportunity to shed light on warp speed delivery of messages with sufficient wisdom to my own personal learning curve. I a mouse-click. (Back then, people have considerably more gray hair and wrote emails regularly exceeding 160 recognize the enormity an ounce or two more of wisdom— characters, complete with punctuation, of medical learning that sufficient wisdom to recognize the proper grammar, and well-organized still awaits me. enormity of medical learning that still thoughts.) awaits me. Raj and I had become fast friends There is one thing that I perhaps in college. We were now both graduate Since then, I have had the regular most appreciate about this adventure students, with an ocean between our chance to share a story with you, the in medicine. Despite the hours, homes and our areas of study. While readers. I hope that this page has despite the occasional frustrations, he aimed to understand the nuances provided you with even a fraction of the and despite the sacrifices required of a of international affairs, I struggled meaning that it has provided me. So durable commitment to the practice of to understand the affairs of the cell. much happens to a patient in the span medicine, there are still those regularly Needless to say, his email updates were of just a day in the hospital or in the occurring moments, made possible by usually more captivating than mine. clinic. So much happens to a medical the patients I meet, which trigger that In a stream-of- spill student/resident/fellow in the span familiar desire to tell a story. of more than 3,000 words, I described of a day. There are moments in any * what had unfolded in the hospital day that might inspire you, moments that day, the experience of watching a that might anger you, and moments After two years of a clinical cardiology fel- family cope with the imminent loss of that simply make you chuckle. This lowship at Johns Hopkins and a research their father. Equally moving was how column has challenged me to do two fellowship at the Duke Clinical Research In- the attending physician assuaged their fundamental things: 1) to first identify stitute, Dan Munoz is currently completing grief. After clicking “send,” I collapsed those reactions of inspiration, anger, or a final year of training and looks forward to into bed. It took my message all of 15 humor, and, perhaps more importantly, a career in academic medicine.

ILLUSTRATION BY SHERRILL COOPER Hopkins Medicine • Fall 2012 • 47 | Post-Op | True to the Core Toward honoring the traditions that have flourished here—and helping them expand.

BY DEAN/CEO PAUL B. ROTHMAN

When you start as a new than a third of medical school leader at an institution, the graduates in the United States possibilities are vast and the leave school owing $200,000 in concerns can be many. When you student loans. At Johns Hopkins walk into a place that is as steeped School of Medicine, the average in tradition as Johns Hopkins is, debt is much lower—close to however, there is an added, powerful $100,000. Of course, that’s still a layer of meaning, one that I find lot of money. One of our major profoundly important. fundraising goals is to increase our Since my arrival here in July, endowment for scholarship funds, and in the six months leading up so that new doctors can leave to my first day on the job, I've Johns Hopkins as close to being had the opportunity to read and debt-free as possible. learn more about the history of our On this issue, and the countless school of medicine, Johns Hopkins, other issues I will embrace in and its many leaders. What I have the months and years ahead, I found, I readily admit, is both will strive to gather ideas and humbling and daunting. It's not advice from people across Johns only that I follow in the footsteps "I will strive at Hopkins Medicine. One of the of Ed Miller, whose great leadership every turn to ensure things I found during my years has allowed me to come in at a as Dean of University of Iowa’s time when Hopkins is thriving; it's that our school of Carver College of Medicine was that also that I stand on the foundation medicine remains the it can be an isolating position. So I forged by so many Hopkins legends, best in the world." really try to get out there and talk to the architects of modern medicine. faculty and students and staff and get Osler, Halsted, Kelly, and Welch. their input. I have lunch with assistant Harvey Cushing, Vivien Thomas, With that said, I want to welcome professors once a month to hear what’s Helen Taussig, Alfred Blalock, Mary our incoming class of medical school happening. I have dinner with students Elizabeth Garrett, Victor McKusick. students. We are starting at roughly once a month. I like to get into the The list is as staggering as it is long. It the same time, and so we will go on hospital and walk the floors a couple is my aim to honor the traditions that our journey together. The Genes to of times a week, and stroll through the have flourished here for more than a Society curriculum is cutting edge, research buildings. Whenever possible, century, and in time, I hope to help and you will feel the full benefits of its I try to have meetings in the offices them grow and expand. It should go approach to how we translate science of faculty and directors so that I can without saying how proud I am to be a and how we care for our patients. meet and talk to people. I intend to part of Johns Hopkins and this legacy The range of learners that we have continue this strategy here at Johns of greatness in medicine. on this campus is remarkable, and Hopkins. I must also offer my sincere thanks I'm equally excited to be starting with With all of these things in mind, I to Ed Miller for everything he has all of our grad and master’s students, offer you this promise: I will strive at done to benefit the health of our PhDs, postdocs, fellows, residents, every turn to ensure that our school patients and our institution, and for and those in our Art as Applied to of medicine remains the best in the so masterfully setting us up for future Medicine program. They represent world. No matter the challenges that success. In the months leading up to the world's next generation of great we will face due to shifts in the health my official start, I was fortunate to scientists, physicians, researchers, and care environment, our core nature will spend time on campus almost once leaders. I am personally dedicated to never change. a week. Dr. Miller was exceptionally fostering their success. We are The Johns Hopkins generous to me with his time and As the father of three, with two University School of Medicine, and his advice, for which I remain very children currently in college, I we will do exactly as our founders grateful. I know that we remain poised am sensitive to the rising costs of and luminaries have done before us. to attract, educate, and train the very higher education, and its impact on We will continue to pass down within best in the field of medicine in large graduates and their families. The New our walls the pinnacle of medical part because of his guidance. York Times has reported that more knowledge. *

48 • Hopkins Medicine • Fall 2012 ILLUSTRATION BY SHERRILL COOPER THE JOHNS HOPKINS UNIVERSITY PRESS Prescribed Reading

Tapping into Depression The Wire and Anxiety The Real Urban Crisis in Later Life Peter L. Beilenson, M.D., M.P.H., What Everyone and Patrick A. McGuire Needs to Know featuring a conversation with Mark D. Miller, M.D., and David Simon Charles F. Reynolds III, M.D. “This book will help both fans— Physical problems and emo- and critics—of The Wire make tional stresses, such as bereave- connections between the sto- ment, health conditions, pain, ries presented on screen and concerns about the future, how public health approaches side e ects of medications, can address vexing and seemingly intractable social problems.” and the accumulated e ects of lifestyle choices, may lead to —John A. Rich, author of Wrong Place, Wrong Time: Trauma and depression or anxiety in older people. However, these mental Violence in the Lives of Young Black Men disorders are not a natural or an inevitable part of aging. Drs. Mark D. Miller and Charles F. Reynolds III show how depres- “Living in Baltimore for most of the ve years that I lmed The sion and anxiety can be avoided or minimized by adapting Wire, I was astounded to see how closely life mirrors art for to changing circumstances while controlling risk factors and too many residents of this—and most other—major cities in getting help when it’s needed. America. I hope the readers of this intriguing book really ‘feel’ A Johns Hopkins Press Health Book the problems that are highlighted and emerge committed to change.” 978-1-4214-0630-5 $14.96 (reg. $19.95) paper —Michael Kenneth Williams, actor, The Wire 978-1-4214-0750-0 $18.71 (reg. $24.95) cloth Systematic Psychiatric Vaccine Evaluation The Debate in A Step-by-Step Guide to Modern America Applying The Perspectives Mark A. Largent of Psychiatry “Mark Largent brings a moving Margaret S. Chisolm, M.D., and personal story, acute cultural Constantine G. Lyketsos, M.D., observation, and deep histori- M.H.S. cal scholarship to the festering foreword by Paul R. McHugh, M.D., and dangerous vaccine debate. and Phillip R. Slavney, M.D. His is a fresh new voice from which we can all learn much.” Johns Hopkins psychiatrists explain the Perspectives approach —Jonathan D. Moreno, Center to evaluating patients with psychiatric disorders. for Bioethics, University of “Psychiatry needs to be saved from itself and this book may be Pennsylvania, and author of The Body Politic: The Battle over a major agent in that e ort.” Science in America —Arnold E. Andersen, M.D., The University of Iowa College of 978-1-4214-0607-7 $26.21 (reg. $34.95) cloth Medicine 978-1-4214-0702-9 $22.50 (reg. $30.00) paper

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