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BURTON ELIAS SOBEL (1937-2013): His Friends Speak From Eugene Braunwald, MD I rst met Burt in July 1964 when he joined the intra- mural program of the National Heart Institute (now the NHLBI) as a Clinical Associate. He spent four months as a clinical fellow on the Clinical Cardiology Service which I headed at the time, and I rounded with him daily. Not sur- prisingly, he had an enormous knowledge base (after all, he was a magna cum laude graduate of Harvard Medical School and had two years of medical house staff training at the (then) Peter Bent Brigham Hospital). But, more impor- tant, he showed great clinical intuitionthat special sixth sense about patientswhich would make him not merely a great, but a truly outstanding clinician. In addition to their clinical rotations, Clinical Associates could choose a laboratory for their research. Although I tried to persuade Burt to join my laboratory, in which we were studying myocardial function, both in isolated cardiac muscle as well as in patients, he made a pivotal and correct decision by declining my invitation politely in order to work in the Experimental Pharmacology section, where he could immerse himself in and be taught cardiac biochemistry by experts. After completing his two year stint at the NIH, which satised his Selective Service obligations, Burt returned to the Brigham for his senior medical residency. His training in biochemistry made him even more attractive to me and I urged, cajoled and pressured him to return to Bethesda and set up a biochemistry laboratory in Cardiology. He did so with rapidity and efciency and rst authored a widely- quoted paper on mitochondrial function in experimental heart failure. When I moved to UCSD as chair of medicine in 1968, I got my clawsinto Burt and convinced him and Susan and several other colleagues to leave the security of the NIH and join me in the adventure of helping to start a new medical school in the desert of southern California. Like a cactus, Burt bloomed in the desert. We worked together on attempting to reduce infarct size in dogs. His role in those early experiments was critical. He set up from scratch both a research laboratory to measure creatine kinase concentration in heart muscle of rabbits with myocardial infarction and simultaneously a new Coronary Care Unit. What I recall most vividly from that period are Burts qualities as a physician. We did not have the luxury of having top notch residents or cardiology fellows during the earliest years and whenever a critically ill patient came into his unit, without being asked and without fanfare, Burt stayed in the unit all night and did what could be done for the patient. This was a great morale booster to the faculty, nurses, medical students, and set a standard for all of our trainees. Burts mood was always upbeat. He was an inveterate optimist and radiated enthusiasm. Then after eight wonderful years together in Bethesda and La Jolla, Burt and I went our separate wayshe to St. Louis and then to Burlington, Vermont, and I to Boston, but the bond between us remained unbroken. He went on to play a seminal role in the development of brinolytic therapy for acute myocardial infarction and in the development of measurements of infarct size in patients. The impact of his research was enormous, but his impact on people was, if anything, even greater. He moved effort- lessly from being a trainee to an independent scientist, to a gifted mentor, to a truly great academic leader, and ulti- mately a senior statesman in cardiology. We have lost one of the great leaders of our eld. Eugene Braunwald, MD Distinguished Hersey Professor of Medicine Harvard Medical School Founding Chairman, TIMI Study Group Brigham and Womens Hospital, Boston Massachusetts E-mail address: [email protected] From Lawrence S. Cohen, MD When I rst met Burt Sobel his family and friends called him Buddy and that is who he was to us for 50 years. Others will chronicle Buddys scientic achievements, which were monumental. I will not repeat them but they have left an indelible mark on the progress of cardiology in the late 20 th century. The time is July, 1962. Buddy was an intern in medicine at the Peter Bent Brigham Hospital (now the Brigham and Womens Hospital) in Boston. I was a fellow in cardiology at that same institution. I received a call one morning while I was in the cardiac catheterization laboratory. The call was about a Manuscript received October 29, 2013; accepted October 29, 2013. 0002-9149/13/$ - see front matter www.ajconline.org http://dx.doi.org/10.1016/j.amjcard.2013.10.007

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BURTON ELIAS SOBEL (1937-2013): His Friends Speak

From Eugene Braunwald, MD

I first met Burt in July 1964 when he joined the intra-mural program of the National Heart Institute (now theNHLBI) as a Clinical Associate. He spent four months as aclinical fellow on the Clinical Cardiology Service which Iheaded at the time, and I rounded with him daily. Not sur-prisingly, he had an enormous knowledge base (after all, hewas a magna cum laude graduate of Harvard MedicalSchool and had two years of medical house staff training atthe (then) Peter Bent Brigham Hospital). But, more impor-tant, he showed great clinical intuition—that special sixthsense about patients—which would make him not merely agreat, but a truly outstanding clinician.

In addition to their clinical rotations, Clinical Associatescould choose a laboratory for their research. Although I triedto persuade Burt to join my laboratory, in which we werestudying myocardial function, both in isolated cardiacmuscle as well as in patients, he made a pivotal and correctdecision by declining my invitation politely in order to workin the Experimental Pharmacology section, where he couldimmerse himself in and be taught cardiac biochemistry byexperts.

After completing his two year stint at the NIH, whichsatisfied his Selective Service obligations, Burt returned tothe Brigham for his senior medical residency. His training inbiochemistry made him even more attractive to me and Iurged, cajoled and pressured him to return to Bethesda andset up a biochemistry laboratory in Cardiology. He did sowith rapidity and efficiency and first authored a widely-

Manuscript received October 29, 2013; accepted October 29, 2013.

0002-9149/13/$ - see front matterhttp://dx.doi.org/10.1016/j.amjcard.2013.10.007

quoted paper on mitochondrial function in experimentalheart failure.

When I moved to UCSD as chair of medicine in 1968, Igot my “claws” into Burt and convinced him and Susan andseveral other colleagues to leave the security of the NIH andjoin me in the adventure of helping to start a new medicalschool in the desert of southern California. Like a cactus,Burt bloomed in the desert. We worked together onattempting to reduce infarct size in dogs. His role in thoseearly experiments was critical. He set up from scratch both aresearch laboratory to measure creatine kinase concentrationin heart muscle of rabbits with myocardial infarction andsimultaneously a new Coronary Care Unit.

What I recall most vividly from that period are Burt’squalities as a physician. We did not have the luxury ofhaving top notch residents or cardiology fellows during theearliest years and whenever a critically ill patient came intohis unit, without being asked and without fanfare, Burtstayed in the unit all night and did what could be done forthe patient. This was a great morale booster to the faculty,nurses, medical students, and set a standard for all of ourtrainees. Burt’s mood was always upbeat. He was aninveterate optimist and radiated enthusiasm.

Then after eight wonderful years together in Bethesdaand La Jolla, Burt and I went our separate ways—he to St.Louis and then to Burlington, Vermont, and I to Boston, butthe bond between us remained unbroken. He went on to playa seminal role in the development of fibrinolytic therapy foracute myocardial infarction and in the development ofmeasurements of infarct size in patients.

The impact of his research was enormous, but his impacton people was, if anything, even greater. He moved effort-lessly from being a trainee to an independent scientist, to agifted mentor, to a truly great academic leader, and ulti-mately a senior statesman in cardiology. We have lost one ofthe great leaders of our field.

Eugene Braunwald, MDDistinguished Hersey Professor of Medicine

Harvard Medical SchoolFounding Chairman, TIMI Study GroupBrigham and Women’s Hospital, Boston

MassachusettsE-mail address: [email protected]

From Lawrence S. Cohen, MD

When I first met Burt Sobel his family and friends calledhim Buddy and that is who he was to us for 50 years. Otherswill chronicle Buddy’s scientific achievements, which weremonumental. I will not repeat them but they have left anindelible mark on the progress of cardiology in the late 20th

century.The time is July, 1962. Buddy was an intern in medicine at

the Peter Bent Brigham Hospital (now the Brigham andWomen’s Hospital) in Boston. I was a fellow in cardiology atthat same institution. I received a call onemorningwhile I wasin the cardiac catheterization laboratory. The call was about a

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Historical Study/BURTON ELIAS SOBEL (1937-2013): His Friends Speak 403

patient who this young intern felt needed an urgent cardiaccatheterization. He was correct. The intern was Buddy Sobel.We met over the patient’s bedside a short time later.

I came home that night for dinner and indicated to mywife, Jane, that I had met a very personable, bright youngintern that day, Buddy Sobel. She said she had met anequally attractive young woman at the supermarket thatafternoon who had asked about the calorie count for acontainer of yoghurt. Her name was Susan Sobel. Couldthey be a couple? They were. The four of us spent a closetwo years together in Boston which formed the foundationfor a half century friendship.

We learned, as young marrieds, that turkeys need to bedefrosted before they were put in the oven for Thanksgivingdinner. We watched Susan develop as a modern dancer.While Buddy introduced us to Tolkien and the Once andFuture King, Susan was devouring Henry James during herpregnancy. Our daughter was born several months beforeJonathan, but his was a more dramatic arrival. Buddy wason service when Susan came in with a placenta previa.

Buddy and I next interacted in 1965, when we were at theNational Heart Institute, he as a Clinical Associate and I onthe staff as head of the clinical program for the CardiologyBranch. Both of us were under the leadership of GeneBraunwald. Early that summer, we received a call that aprominent researcher at the Heart Institute was beingbrought in with what sounded like a heart attack. Indeed, itwas. His electrocardiogram had all of the characteristics ofan acute heart attack involving primarily the right ventricle.His blood pressure was 90/60 mm Hg. The first articledescribing the proper therapy for patients with right ven-tricular infarction had yet to be published. The propertherapy is now quite basic and is part of Cardiology 101. Ina patient with a right ventricular infarct the proper therapy isto give a large intravenous volume of fluid. The wrongtherapy is to give medications aimed solely at raising theblood pressure. On that warm summer day Cohen and Sobelgave only small amounts of intravenous fluid and gave anabundant quantity of adrenalin-like drugs to raise his bloodpressure. I am happy to tell you that the researcher survived,perhaps in spite of our ministrations, not because of ourministrations. He lived for another productive twenty years.

After Buddy moved to San Diego and then to Barnes, wesaw each other at heart meetings where he shared his pride inthe achievements of Jonathan and Elizabeth as they grew, andin Susan’s success as a family therapist. His favorite meetingswere those at which he could find a piano or a ski slope,because his love of music and passion for skiing, almostmatched his love of medicine. I wish I could say that thebrilliance he demonstrated in the laboratory, in the clinic, andon the podiumwas also apparent in his early choice of clothes,but by the time Buddy was at the peak of his profession; histaste had markedly improved, prodded by my wife Jane.

Buddy’s sense of humor was acute and nowhere was itneeded more than in 1979 when five cardiologists were on athree-week scientific interchange in China. At the time ofour visit, hostages from our Iranian embassy were beingheld in Tehran. We found ourselves stranded in Xian due toa windstorm from Mongolia which we were told, preventedplanes from returning to Beijing. In the military barracks,five men had only the clothes on their backs and one book

that Buddy had brought with him. He dismembered thebook so that we could each have chapters to occupy our-selves and he somehow got word back to Susan that wewere not in need of ransoming as yet. Buddy kept one of thephysicians from becoming unglued at the thought of notbeing able to get back in time for an important meeting; andprevented panic from setting in when we saw only Iranairliners on the tarmac when we finally landed in Beijing.

Liz Sobel provided another point of contact for Buddyand me. Coincidentally, she and our older daughterhappened to be on the same bike trip as teenagers andrecognized the names they had heard throughout theirchildhoods. The two became friends. Then, Liz attendedWesleyan which is 45 minutes from where we live. Onceagain, we were able to spend Thanksgiving with the Sobels’and get to meet Don when he and Liz began dating.

In his later years, when he was in Vermont, Buddycontinued to send me books. The Art of War by Sun Tzuand the End of Faith by Sam Harris were two of his fa-vorites. He gave us updates on Jonathan’s legal career whichhas been as stellar as Buddy’s own in medicine. He learnedabout the intricacies of advertising and the wine industry ashe kept pace with Liz and Don’s lives. He embraced hisdaughter-in-law and grandparenthood. He marveled atSusan’s ability to rehab after painful knee surgery and attackthe slopes with her usual vigor.

When Buddy developed cancer, he researched his diseasewith the same probing intellect that he brought to Cardiol-ogy. His love of his family, his passion for his work, hisdevotion to his colleagues and friends, his optimism and hishumor remained undiminished. It is we who feel diminishedby his loss.

Buddy, we will always miss you.

Lawrence S. Cohen, MDThe Ebenezer K Hunt Professor of Medicine (Emeritus)

Yale University School of MedicineNew Haven, Connecticut

E-mail address: [email protected]

From Robert Roberts, MD

I had the great privilege and good fortune to have BurtSobel as a mentor and friend for 11 years. My researchcareer started in Burt’s laboratory in San Diego andcontinued at Washington University in St. Louis. Burttransformed Cardiology through his research and scientificcontributions which are well documented in the memoriampublished in the Journal of the Society of ExperimentalBiology and Medicine.

Burt was always in a thinking mode with relentless en-ergy to meet the challenge. He was excited and stimulatedby the underlying biology of disease. Burt initiated hiscareer at the NIH where the concept of a triple threat waspossible and would become the sought after goal by aca-demic physicians of his generation. While Burt is recog-nized primarily for his scientific contributions, he was agreat clinician at the bedside which he demonstrated in hisposition as Head of the CCU in San Diego. Everyonelocally, nationally and internationally admired Burt’s abilityto talk at the podium or on a one-to-one basis. His skills as a

404 The American Journal of Cardiology (www.ajconline.org)

clinician, researcher and educator were only exceeded by hisadministrative talent as demonstrated by his success asChief of Cardiology, Editor of Circulation and Head ofMedicine at the University of Vermont.

His awesome intellect, his attention to details, methodicalapproach and laser sharp focus enabled him to achieve hismany successes in fulfilling his roles as clinician, educator,researcher and administrator.

Burt was of course much more than that, in addition tobeing a great family man, he was a great pianist, orator andthinker. Burt enjoyed pondering the fundamentals of scienceand assessing their role in society. Burt offered inspirationand optimism on a daily basis and was intellectually chal-lenging to himself and everyone around him. Burt’smentorship and confidence in me was markedly influentialin shaping my academic maturity and also my subsequentacademic career. My memories of Burt as a mentor andcolleague have forever been with me daily and will continueto shine brightly.

Robert Roberts, MDPresident and Chief Executive Officer

University of Ottawa Heart Institute, Ottawa, CanadaE-mail address: [email protected]

From Steven R. Bergmann, MD, PhD

In the journey of life, we meet many people. Somebecome fleeting, passing memories, but every now and then,a special person comes into your life who profoundly moldswho you are. I was lucky enough to have Burton E. Sobel,M.D. (Burt) be one of those persons.

Because of his interest in adjunctive therapies to reper-fusion, Burt was sitting in the audience when I presented mythesis research on the effect of moderate hypothermia onreperfused myocardium at the Federation for AmericanSocieties for Experimental Biology (FASEB) meeting in1977. He came up to me after my presentation and describedPET—newly developed at Washington University and thathe was sure it would be interesting to use to better under-stand my results. He continued to tell me why perfusion andmetabolism underlie the mechanical effects that were thesubject of my research, and convinced me that I should joinhim at Washington University. That chance encounter in1977 developed into a 35-year friendship that shaped notonly my investigational career, but also the person I amtoday.

Burt’s enthusiasm for investigation, his thirst forknowledge, his zest for life, and his smile, were infectious.Burt was involved in so many different aspects of cardiol-ogy research that it was dizzying. However, every memberof the Division knew that they were an important piece ofsomething great, and the productivity that came out of theWashington University labs under Burt’s leadership wasremarkable.

Burt stressed the importance of preparation. He came intomeetings extraordinary prepared and expected the same ofyou. Burt always felt that asking the hard questions that youmight get at a meeting was best done among friends andcolleagues before the actual presentation. Preparation wouldstart months before a big meeting. Fellows and faculty were

grilled with questions over and over again. Papers weresubject to revision after revision until, in Burt’s mind, theywere as perfect as they could get. That kind of preparation,rehearsal, and revision were the hallmarks of how Burtpursued important scientific questions and all of the fellowsand colleagues with whom he worked knew that they wereworking with one of the smartest and most forward thinkingindividuals in the field. Burt could be hard on you if youwere not living up to the potential he saw in you. But bypushing hard, he brought out your best, and you grew as ascientist, clinician, and as a person.

My fondest memories of Burt were the times that wespent outside of the lab. In addition to sessions at his homehoning papers, preparing grants, and working on pre-sentations, Burt and I often went canoeing or sailingtogether. He was competitive at these endeavors as well. Iremember one time canoeing in an Ozark stream in the earlyspring when the water was high, and his canoe, with his wifeSusan aboard, capsized. My first thought was how I wouldbe responsible for his hypothermic arrest. But Burt, resilientas ever, popped out of the water, albeit cold and wet. Heremembered that adventure fondly and with a laugh. In oneof the last memos that I received from him, he copied me onthe work order to his marina for getting his sailboat readyfor the upcoming season. He wanted to know if there wasanything he had left out. There was not.

I am not going to outline the contributions that Burt madeto the field of cardiology, as these are well documented byBurt’s own prodigious publication record and the greatnumber of scientist and clinicians he trained. He cherishedhis colleagues and his family—wife Susan and childrenJonathan and Elizabeth. I will close by saying that he wasthe best mentor and a dear friend. His sudden death leaves adeep, deep void. All who knew him were greatly blessed.

Steven R. Bergmann, MD, PhDChief, Thomas Killip Division of Cardiology

Vice Chair, Department of MedicineBeth Israel Medical Center

New York, New YorkE-mail address: [email protected]

From Allan S. Jaffe, MD

Burton was so bright, so insightful and so interested ineverything that knowing him meant endless and consistentstimulation about almost any topic whether it was science,the role of physicians in Nazi Germany, calculus, or base-ball. The answer to each question led to another until thetopic was digested or delayed so more investigation couldbe done. That approach to life that was endemic in the manled to a wonderful, visionary and committed scientist. Burtwas at every turn totally committed to good science wher-ever it led. He had the foresight to see the potential of ul-trasound long before it was appreciated by cardiologists, hesaw the potential impact of positron tomography at an earlystage and the possibility that t-PA would be a game changer.In his later years, he saw the links from his cardiovascularand hematologic interests to diabetes. If there is a heaven,Burt is likely trying to figure out why he did not know thatbefore he experienced it.

Historical Study/BURTON ELIAS SOBEL (1937-2013): His Friends Speak 405

He was equally insightful about people and his decisionsabout them were invariably astute. He knew not only how tomotivate but also who would fit with into a given situationbest. He was for that reason, a good friend. When one hadproblems, one always could know that Burt would help.That did not mean Burt was easy. He demanded commit-ment to science and productivity in that realm and was notinclined to hear excuses easily. On the other hand, heworked so hard every day of the week and often late into thenight, that the excuse of not having enough time was hard toemploy. He led by example.

Burt cared passionately about young people who were inhis view “our future.” It is even now not clear whether thatwas more of a priority than even his science but he was awonderful mentor and his former fellows all cherished theirability to see him again and spend time with him. He was toso many an indispensable part of their growth and devel-opment. His legacy can be tabulated in his hundreds ofmanuscripts, editorials, books, guest lectureships and thelike but it will be amplified many fold by those who hetaught how to think about the problems of science and oflife. The world in many ways is a much better place forhaving Burton Sobel as part of it.

Allan S. Jaffe, MDProfessor of Medicine and Professor of Laboratory

Medicine and PathologyMayo Clinic, Rochester, Minnesota

E-mail address: [email protected]

From Satoshi Fujii, MD, PhD

Inspired by his invited special lecture at Japanese Circu-lation Society in Kyoto in 1985, I joined the laboratory of Dr.Burton E. Sobel in the Cardiovascular Division at the

Washington University in St. Louis in 1987. WashingtonUniversity was the place to be for any international cardiol-ogist interested in thrombolysis. At that time Burt and I hadsignificant and wonderful scientific discussions. I was tryingto convince Burt that PAI-1 played a major role in tissueremodeling in addition to thrombolysis. After I returned toJapan I enjoyed continuing collaborative research with hisrecent research focused on diabetes and coronary arterydisease.

Dr. Sobel was my mentor, longtime friend and colleague.His international fellows will always remember his brilliantteaching skills and gracious sense of encouraging others inaddition to his distinguished research. He was a verycaring leader and quick in establishing close relationshipwith his new research fellows. He was kind enough to takeme out for outdoor activities when my experiments were notgoing well. His clinical research presentations on throm-bosis and thrombolysis at Japanese Circulation Society in1985 and at Japanese College of Cardiology in 1997 havedeeply influenced the cardiology practice in Japan. BecauseBurt and his wife, Susan, loved skiing my wife and Ienjoyed guiding them to XI Winter Olympic facilities inSapporo.

He had a creative mind and could apply his intellect tosolving basic science problems for answering clinicalquestions. My thoughts often turn to our original friendshipand vigorous scientific debate on thrombolysis.

Satoshi Fujii, MD, PhDProfessor, Department of Molecular and Cellular

Pathobiology and TherapeuticsNagoya City University Graduate School of Pharmaceutical

Sciences, Nagoya, JapanE-mail address: [email protected]