ASCI Presidential Address Mentoring and Teaching Clinical Investigation

ASCI Presidential Address Mentoring and teaching clinical investigation

Kenneth Kaushansky

J Clin Invest. 2004;114(8):1165-1168. https://doi.org/10.1172/JCI23462.

ASCI Presidential Address Supplement

A man walking along a road comes across three bricklayers. When asked what he is doing, the first bricklayer replies, “I am laying bricks.” When asked the same question, the second bricklayer answers, “I am making my living.” When asked what he is doing, the third bricklayer steps back, looks around, and responds, “I am building a cathedral.” It is my great privilege and pleasure to address the ninety-sixth annual meeting of the American Society for Clinical Investigation. I will begin with many thanks: to the council members who provide sage advice and a critical eye; to our staff, who provide dedicated direction and a keen sense of corporate memory; to the members of the ASCI in 2001, who felt it appropriate that I serve on the ASCI Council; and to the Presidents who have come before for providing the insights and precepts that have helped shape our Society into an organization of extremely dedicated men and women that continues as the leading advocate for scholarship in medicine. I will also try to follow the advice of the seventeenth-century Catalan philosopher Baltasar Gracian, who stated, “What is good, is doubly so if it be short; and in like manner, what is bad, is less so if there be little of it.” Most recent Presidential Addresses have begun with a palpable […]

Find the latest version: https://jci.me/23462/pdf Supplement ASCI Presidential Address Mentoring and teaching clinical investigation Kenneth Kaushansky, M.D.

A man walking along a road comes across three Seldins. We have a distinguished history often, and teach widely. And we must teach bricklayers. When asked what he is doing, the first and an outstanding cause, and I applaud the grand landscape — the larger context of bricklayer replies, “I am laying bricks.” When asked the members of the ASCI. clinical investigation — to demonstrate to the same question, the second bricklayer answers, In reading over prior Addresses, I was each of these groups how the act of asking “I am making my living.” When asked what he is struck by the many recurring themes that scientific questions with a clinician’s intu- doing, the third bricklayer steps back, looks around, our past presidents chose to highlight: the ition can build “cathedrals.” and responds, “I am building a cathedral.” spirit of science, the imbalance between MD and PhD biomedical researchers, financial Teaching medical students and It is my great privilege and pleasure to support for clinical investigation and the residents the power of clinical address the ninety-sixth annual meeting of favorable economics of investing in bio- investigation the American Society for Clinical Investiga- medical research, and diversity in the ranks The US Public Health Service initiative tion. I will begin with many thanks: to the of American academic medicine. But of all Healthy People 2010 lists the major national council members who provide sage advice the challenges facing us as a Society within health concerns: tobacco use, substance and a critical eye; to our staff, who provide our broader society, I am most concerned abuse, cancer, osteoporosis, diabetes, cardio- dedicated direction and a keen sense of cor- about our ability to mentor and teach our vascular disease, immunization and infec- porate memory; to the members of the ASCI learners, and am frequently reminded of tions, blood pressure, nutrition, sexually in 2001, who felt it appropriate that I serve the pure joy that endeavor can bring to the transmitted diseases and many others (1). on the ASCI Council; and to the Presidents physician-scientist. The theme of the program argues that all who have come before for providing the Rather than being intimidated by the citizens should have a better understanding insights and precepts that have helped shape prospect of having my remarks compared to of those factors that affect personal health. our Society into an organization of extremely those of Presidents past — such as Joe Gold- I would argue that to achieve this goal we dedicated men and women that continues as stein’s insightful 1986 talk formulating the need both a citizenry that understands the the leading advocate for scholarship in medi- malady of insufficient technical training and processes of science and medicine, as well as cine. I will also try to follow the advice of the consequent lack of courage in junior faculty high-quality students selecting a career in seventeenth-century Catalan philosopher which I paraphrased to a group of junior fac- the science of medicine to do today’s work. Baltasar Gracian, who stated, “What is good, ulty members just last week, or Tom Stossel’s Of the plethora of enjoyable tasks of is doubly so if it be short; and in like manner, witty and wise apocalyptic fable in 1987’s being a Chair of a Department of Medicine, what is bad, is less so if there be little of it.” Brave New Medicine, or Ed Benz’s 1992 cel- one of the most enjoyable is speaking with Most recent Presidential Addresses have ebratory Presidential remarks — I relish the fourth-year students while preparing their begun with a palpable angst, prompted chance to convince you that perhaps our letters of recommendation. While basking by one of the major challenges of ASCI greatest challenge as advocates for the physi- in their enthusiasm for the upcoming years leadership — preparation of the Address cian-scientist is the issue of teaching. of residency, I always manage to inquire itself. Although I cannot speak for others, We must teach, teach often, and teach whether they appreciate the connections my apprehension was due to the sense of widely. We must teach medical students the between their first two years of basic sci- awe that developed while carrying out the rewards of marrying scientific inquiry and ence curriculum and their third and fourth unwritten oath of office requiring each clinical medicine; we must teach residents years of clinical rotations. Although an President to read the prior Addresses in that the singular discovery of new knowledge occasional student sees the relationship, the months prior to the annual meeting. can sometimes impact tens of thousands of most do not. Rather, they usually express The angst of writing the Address comes patients; we must nurture our fellows and great joy in shedding the shackles of class- from considering the accomplishments junior faculty members, providing them the room work for “real medicine” — interview- and panache of the individuals who have tools of the trade and instilling in them the ing and examining patients, formulating a previously held the ASCI gavel and used tremendous excitement that comes from differential diagnosis, doing scut work, this pulpit to espouse acute wisdom and solving the mystery of an idiopathic disor- and watching their patient rise from the uncommon insight and to create new pro- der or bringing effective therapy to patients. near dead and walk out of the hospital. fessional diagnoses and level outstanding And because teaching can impact these con- They often miss, for example, the integral wit — the Clem Finches, Joe Goldsteins, stituencies, we must teach the public about significance of the immunology they stud- Holly Smiths, Gene Braunwalds, and Don the values and processes and power of bio- ied in their second year to the survival of medical science, replacing the fear of things their patients’ renal allografts, or how the This article is adapted from a presentation at the unknown with a renewed enthusiasm for molecular biology they labored over makes ASCI/AAP Joint Meeting, April 16–18, 2004, in Chicago, Illinois, USA. the reward and potential made possible by the diagnosis of tuberculosis or AIDS so Citation for this article: J. Clin. Invest. 114:1165–1168 strong support for clinical investigation. To much quicker and easier, or how the signal (2004). doi:10.1172/JCI200423462. reiterate: it is clear that we must teach, teach transduction studies they slept through

The Journal of Clinical Investigation http://www.jci.org Volume 114 Number 8 October 2004 1165 supplement in cell biology yielded the development of a remarkable new drug for patients with Table 1 chronic myelogenous leukemia. Many just Examples of resident research blocks, 2002–2003, University of California San Diego don’t get the connection — they do not see the cathedral — and we must fix this N-glycolylneuramic acid, a common mammalian sialic acid no longer endogenously situation. We must offer bench-to-bedside produced by man opportunities to illustrate — some might p38 MAPK activation in human tissues: Modulation by insulin, obesity and type II diabetes say indoctrinate — the power of transla- mellitus tional medicine throughout the four-year Cardiomyopathy associated with methamphetamine abuse medical school curriculum. Academic medicine is just beginning Assessment of coronary flow reserve using myocardial contrast echo to pay attention to this issue. Three years Purification of surfactant protein D and development of an ELISA for measuring levels in ago, the Mount Sinai School of Medicine BAL fluid introduced a full-time three-week course for first-year students that emphasizes the techniques, and enhanced their ability to One strategy our residency program and link between basic science concepts intro- critically evaluate a medical or scientific others have used to address this trend has duced at the bench and the clinical care of manuscript. Perhaps most importantly, been to implement a research elective block. patients. The goal of the course was to reen- 85% responded that the project impacted It appears such programs are quite popular ergize students’ career choices by allowing their careers in medicine. (3). with residents and impact their career deci- them to experience an in-depth, bench-to- In addition to medical students, I believe sions. In our first year of offering research bedside look at a particular topic in medi- resident physicians are equally critical to blocks, nine residents spent two to three cine. At the completion of the first such the mission of repopulating academic months in the laboratory of a faculty mentor offering, most students commented that medicine. Many of my predecessors have and then presented their work at a wonderful the program successfully helped them to spoken of the “pipeline” problem and research symposium late in the year where overcome their end-of-first-year blues and how MD/PhD or medical scientist train- we brought in good San Diego Mexican food that the course should be continued. Addi- ing programs (MSTP) are ideal means of and enjoyed a night of science, camaraderie, tionally, many recommended additional providing well-trained individuals ready to and mentoring. And because of this effort, topics for future study. The creators of this assume the ranks as productive physician- I believe we witnessed many residents see- approach, Herold, McArdle, and Stagnaro- scientists and leaders of academic medi- ing the cathedral for the first time. The last Green, believe the program promotes the cine. Although MSTP programs are clearly two years have seen seventeen and nineteen development of physicians with an appre- an outstanding source of future members of our residents enlist in scientific electives; ciation of the scientific basis of disease (2). for the ASCI and AAP, the level of support some of the titles of their projects are shown Another avenue to instill in students for these and other such programs is not in Table 1, demonstrating that their work is a strong appreciation for the science of keeping pace with the demand, despite not trivial in scope or level of sophistication. medicine is an independent study project intense and persuasive lobbying efforts. I doubt many in this audience will dis- (ISP) designed to develop the self-directed Moreover, we are not keeping some MSTP agree that these two groups, medical stu- thought and problem-solving abilities students “on task.” As a department chair dents and residents, are our best substrate necessary to optimize a career in medicine. at a research-intensive school with a vigor- — the most likely population on whom we But we must go beyond merely providing ous MSTP program, each year I still come can draw the next generation of talented the opportunity; we must be certain the across several MD/PhD graduates who are clinical investigators and physician-scien- projects are rigorous, carefully mentored, more interested in a career that allows “civi- tists. However, it is also clear that this sub- and that they utilize scholarly methods to lized” work hours, high salaries, and ready strate is very volatile, one sensitive to the investigate and generate new information. access to recreational facilities than they discouraging word. While on my first inter- Examples of recent ISPs at our institution are in the pursuit of academic medicine. view for my present day job I asked to speak include Protein Kinase A Gene Therapy, A second important source of nascent with the chief medical residents. Although Angiogenesis in Tumor Metastasis, and physician-scientists is a much larger group my employer — a late-bloomer physi- B-type Naturetic Peptide for Early Detec- of “late bloomers,” a term used by Ajit cian-scientist with impeccable credentials tion of LPS-Induced Cardiac Dysfunction. Varki in his 1999 Presidential Address to himself — found the request a little odd, There is now evidence that such research describe physician-scientists like himself I learned a great deal from my interaction projects are viewed favorably by students. and me, whose scientific spirit was kindled with these bright and energetic mirrors. I For example, William Frishman has shown during medical school, residency or fellow- soon learned from them that many in the that an intensive six-month mentored ship. Unfortunately, the number of late- faculty were dissatisfied, angry over com- research project, replacing traditional clin- bloomer physician-scientists has declined pensation and a perceived lack of support ical electives and carried out in the fourth impressively during the past two decades. for scholarly activities. This perception was year at the Albert Einstein School of Medi- We must correct this trend by cultivating held by a small but vocal minority of indi- cine, was very favorably reviewed. An over- science in our residents and fellows, help viduals who had frequent contact with the whelming number of the responding stu- them to see the cathedral in the bricks, house staff, and although this was clearly dents reported that the research increased and thus provide the large number of late- an extremely talented group of young phy- their ability to formulate a hypothesis, blooming physician-scientists needed to sicians, all four chief residents have since furthered their knowledge of research repopulate our species. left or plan to leave academics for practice.

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Thus, it is clear that the messages we send ing needed to follow a path of laboratory- remains crucial (5). I would add that funding to our charges can be devastating or inspir- based investigation wherever it may lead. is not enough: teaching and mentoring are ing; the choice is ours. However, in this age of translational medi- vital complements to financial support. In addition to showing lack of support, cine, the basic or disease-oriented researcher Despite all of the recent attention focused some academic faculty send a perhaps even is not the lone sufferer of PAIDS; it can strike on clinical research as a means for trans- more pernicious message: teaching and men- burgeoning clinical investigators. Concern lating basic discovery into patient care, for toring students and residents can be left to for the health of this group of investigators is translational research to flourish, the basic others. Many of our most successful physi- easily illustrated; for example, the proportion biomedical science and disease-oriented cian-scientists are playing far less of a role in of physician researchers applying for clini- research communities must remain innova- academic departments so they may concen- cally oriented NIH grants declined from 40% tive and strong. It is a common observation trate their efforts solely on scientific pursuits. of total applicants in 1972 to 25% in 1997 that biomedical science is changing radi- I couldn’t more strongly disapprove of this (4). In response, several new initiatives have cally; perhaps the most obvious pillar of the abandonment of students and residents. If been forthcoming. The NIH has launched previous era of medicine to crumble is the we are to do more than pay lip-service to the the K23 program, a mentored clinical inves- organization of research around clinically career pathway of clinical investigation, the tigator award, and funded 152 such awards defined disciplines of medicine. Although I most successful physician-scientists must in 2001. Moreover, private foundations, am a card-carrying hematologist, my labora- become highly accessible to these learners. such as the Doris Duke Charitable Founda- tory studies the molecular mechanisms by This accessibility could take the form of par- tion, the Burroughs Wellcome Fund, and the which cytokines influence blood cell devel- ticipation in morning report, the giving of Howard Hughes Medical Institute, have also opment. In the present era of biomedicine professors rounds or grand rounds, or even established programs to support young clin- it makes as much sense for my laboratory attending on a general medicine service, ical researchers and their mentors. But now to be located adjacent to a rheumatologist where individuals could use their experience that financial support for clinical investiga- studying the effects of TNF on rheumatoid as both physicians and scientists to encour- tion has rebounded, the next weakest brick synoviocytes, or adjoining an endocrinolo- age their fellows and students to make the in the cathedral is teaching and mentoring. gist who studies the signals generated when vital connections between the art and sci- All too often, although grant or departmen- insulin binds to its receptor on a myocyte, ence of medicine — to paint a picture of the tal dollars provide junior faculty time pro- as it is to be contiguous with another hema- cathedral. Taking on a service responsibility tected from high-throughput clinical care, tologist who studies the structure of globin. provides an added dividend: not only will many leaders in academic medical centers It is critical to place basic biomedical and successful physician-scientists and clinical expect nascent clinical investigators to form disease-oriented physician-scientists — espe- investigators serve as outstanding role mod- by spontaneous generation. Although our cially new investigators — amidst neighbors els to many, they will free up junior faculty emerging clinical investigators are excellent who can provide critical and enthusiastic from some of their clinical responsibilities, clinicians, they are not yet excellent inves- mentoring. Such influence has the poten- allowing the latter the time necessary to tigators. I would argue that contemporary tial to both enhance investigators’ skills as develop their investigational skills. Moreover, clinical research requires a new model for well as instill in them the excitement that is although I might be a chorus of one, I would training investigators, one that leads to the academics, the spirit of science. even counsel successful physician-scientists design and execution of clinical trials that I spoke earlier of the impact of negative to take the further step of “going over to the answer more questions than they raise. We comments from senior faculty; in my view dark side” to assume the chairmanship of a must continue to participate in and support a second source of negativism is the edito- medicine, pediatrics, or pathology depart- the development of innovative teaching and rializing that abounds in times of perceived ment. Here, too, late bloomers are vital: of mentoring programs as they are our incuba- fiscal hardship. Junior faculty members and the many physician-scientists who presently tors for the clinical researchers of the twenty- transitioning fellows are too often discour- serve as chairs of departments of medicine in first century. Such programs should combine aged when they read editorials stating that the US, only two have been trained in tradi- seminars in which senior clinical investiga- the physician-scientist is a dinosaur, that tional MSTP programs. tors describe their own work with didactic physician-scientists are neither physicians training in clinical research methods, includ- nor scientists, or that funding is impossible. Provide fellows and junior ing courses in clinical trial design, biostatis- We were recently attempting to recruit a faculty members the training tics, bioethics, and clinical research methods, junior faculty member, an MD/PhD-trained and environment they need and include faculty-mentored research proj- medical subspecialist, who, despite having to be successful ects. Our particular version at the University penned twelve strong publications, having It is clear that no matter how impressive the of California, San Diego, is termed Clinical been allotted 80% time for research, and molecular discoveries made at the labora- Research Enhancement through Supple- having been successful in obtaining a K08 tory bench, they can only be translated into mental Training, or CREST. The program is award, was convinced that his upcoming remedies for human disease by physicians funded by one of the fifty-seven K30 awards R01 application was doomed. One approach who engage in clinical investigation. As I from the NIH. Although David Nathan and to address this crisis in confidence is to cre- mentioned earlier, in 1986, Joe Goldstein Jean Wilson concluded that the net result of ate a nurturing environment with strong spoke of a syndrome of insufficient training, efforts such as K23 and K30 awards has been mentors. As Ed Benz suggested in his 1992 which he called Paralyzed Academic Investi- “to diminish the aura of discouragement Presidential Address, in each of our pasts gator Disease, or PAIDS. This syndrome is and crisis surrounding clinical investiga- someone motivated us to give research a try, epitomized by the young investigator whose tion,” they also argue that continued, careful made us feel good about our chances for career is stuck for the lack of technical train- attention to the support of clinical research success, and served as a role model for how

The Journal of Clinical Investigation http://www.jci.org Volume 114 Number 8 October 2004 1167 supplement the life of a physician-scientist can be highly be eliminated in ten years, are toxic to the derived from the smile that punctuates a rewarding. The quality of our contacts with public trust and can have a chilling effect on successful Socratic discussion with students these people — our mentors — probably scientific credibility. and residents, acknowledging they finally had a greater impact on our career decision From what I have seen and read on the got it, by the contentment that comes with choices than any other single factor. subject, we in biomedicine are very much in the first publication or first grant obtained need of more Carl Sagans. Sagan played a by your fellow, or by the pride in seeing some- Teaching the public that scientists leading role in the American space program one you mentored promoted to professor or are creative and caring, and that from its inception. As a consultant to NASA, elected to the ASCI. I would submit the fol- science can be harnessed to he briefed the Apollo astronauts before their lowing question to you: can we really afford improve the state of human health flights to the Moon and designed many of not to teach? Teaching is what we are all If we are successful in the efforts I’ve the scientific experiments carried on the about. It is good for the soul, and without it described thus far, our students, residents, unmanned Mariner, Viking, Voyager, and our Society and all it stands for will become fellows, and junior faculty will understand Galileo expeditions to the planets. He con- a footnote in the ancient history that was that biomedical science must be robust and tributed to our understanding of the high clinical investigation. I encourage all of you based on the logical application of rigorous temperature on Venus (a massive green- to teach and mentor more bricklayers who methods and objective analyses, with conclu- house effect), the seasonal changes on Mars will in turn build more cathedrals. sions coming only from a careful assessment (due to windblown dust), and the reddish of all the evidence. Unfortunately, if that is haze of Saturn’s moon Titan (composed of Acknowledgments all we do, we may still fall short of improv- complex organic molecules). For twelve years Given these comments on mentors and ing the state of clinical investigation. When Carl Sagan was editor-in-chief of the journal mentoring, I wish to express my great thanks our Society was founded in 1908, the gap Icarus, the leading professional publication to many individuals who mentored me and between the biomedical knowledge base of devoted to research in the planetary sci- in so doing taught me the value of mentor- the seventeen charter members and society ences. He was the co-founder and first presi- ing: Clem Finch, a former ASCI President at large was wide, but this gap has grown dent of The Planetary Society, and a Distin- who convinced me that hematology holds substantially wider with each passing decade. guished Visiting Scientist at the California many biochemical and molecular biological As it widens, so too does public distrust in Institute of Technology. In short, Sagan was rewards; Earl Davie, for bringing humor to our profession. Many recent polls point to a scientific nerd and an accomplished leader the laboratory and teaching me to remain large numbers of the public who believe the in his field, much like many of the members focused on good projects; ASCI members sun rotates around the earth, in extrasen- of our Society. But few outside of scientific Barry Coller, Andy Shaffer, and Ed Benz, the sory perception, and that evolution is only circles remember Carl Sagan for these con- latter of whom is also a former ASCI Presi- a theory. I would argue that we must close tributions; rather, Sagan is remembered for dent who counseled me that being a Chair this gap between science and the public if we bringing science to the public. His Pulitzer of Medicine can be gratifying, fulfilling, and are to improve the state of clinical investiga- Prize-winning book Cosmos remains the important; and John Adamson, who taught tion. We must teach that scientific innova- best-selling science book published in the me the value of scientific excitement, integ- tion is the key to improved health and must English language. The Emmy and Peabody rity, and of always asking the next question be expanded, not, as some cynics proclaim, Award-winning television series based on his — not to mention for investing much red bridled because of adverse effects on health book has been seen by 500 million people in ink in my first few manuscripts. Lastly, and care economics. We must encourage public 60 countries. As a result, Carl Sagan received most importantly, my wife Lauren and our understanding of the necessity of revision to the 1994 Public Welfare Medal, the highest children, Alexis and Joshua, whose patience, scientific theories and explain that re-exami- award of the National Academy of Scienc- understanding and literary, scientific, and nation of past conclusions is axiomatic to es, for distinguished contributions in the political discussions are awe-inspiring. rigorous science. For example, when new application of science to the public welfare. studies reverse the existing recommenda- The award reads “[H]is ability to capture Address correspondence to: Kenneth tions for estrogen therapy of post-meno- the imagination of millions and to explain Kaushansky, Professor and Chair, Depart- pausal women, it’s because the study was difficult concepts in understandable terms ment of Medicine, University of California, finally done the proper way. We must teach is a magnificent achievement . . .” I would San Diego, 402 Dickinson Street Suite 380 the fundamental importance of biomedicine argue the study of science in medicine is San Diego, CA 92103-8811. Phone: 619- to society and respond to the challenges of just as moving as that of the planets, and 543-6170. Fax: 619-543-3931. E-mail: anti-scientific attitudes. Imagine what the just as relevant, if not more so, to the public [email protected]. state of biomedical investigation would be welfare. Like astronomy, medicine needs its if we had a scientifically literate electorate or Carl Sagans to improve public understand- 1. http://www.healthypeople.gov/document. 2. Herold, B.C., McArdle, P., and Stagnaro-Green, A. the willingness of patients to participate in ing and perception. 2002. Translational medicine in the first year: inte- clinical investigation. But we must be careful Many of you have heard me state my belief grative cores. Acad. Med. 77:1171. not to step over the line of ethical science or that the pursuit of a career in academic 3. Frishman, W.H. 2001. Student research projects to offer expectations that cannot possibly be medicine is a genetic disorder, display- and theses: should they be a requirement for medical school graduation? Heart Dis. 3:140–144. fulfilled. Claims such as those made in 1982 ing autosomal recessive inheritance: you 4. Nathan, D.G. 1998. Clinical research: perceptions, that an AIDS vaccine was only a year or two need two mutant alleles to be so afflicted. I reality, and proposed solutions. JAMA. 280:1427– away, or those in 1985 that gene therapy is would argue that one of the phenotypes of 1434. 5. Nathan, D.G., and Wilson, J.D. 2003. Clinical just around the corner, or those last year this genotype is the need to teach. The need research and the NIH — a report card. N. Engl. J. that death and suffering from cancer will is fulfilled by the great sense of satisfaction Med. 349:1860–1865.

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