American Society of Hematology

Inside TRTH

David Sykes, MD, PhD
Fabienne McClanahan, MD

Published on: July 01, 2013

1. Assistant in Medicine at Massachusetts General Hospital and Instructor of Medicine at Harvard Medical School

2. PhD Student, Centre for Haemato-Oncology, Barts Cancer Institute, University of London

This year marks the fourth anniversary of the Translational Research Training in Hematology (TRTH) program, a joint venture between the American Society of Hematology (ASH) and European Hematology Association (EHA). The yearlong teaching and mentoring program was developed to support and encourage careers in translational hematology.

The 2013 spring course brought together an international cadre of 20 trainees and 16 faculty members who met at the Villa Gallarati Scotti, a picturesque Italian villa-turned-conference-center outside of Milan. Once the gates of the estate closed behind the airport shuttles, we were cloistered for six days during which we were immersed in formal didactic sessions and intense small-group discussions, intermixed with lively, informal mentoring events.

Introductions were made over a welcome luncheon where the initial advice from the faculty focused on how to operate the intimidating espresso machine and how to avoid the temptation of the plentiful and delicious Italian desserts. We had come prepared with brief presentations and thus spent our first afternoon outlining our research projects and answering enthusiastic questions from other trainees. Fueled by caffeine and cookies to stave off jet lag, we universally exceeded the 15 minutes assigned to each presentation, and this initial session lasted well into the evening. Dinner was a boisterous affair as faculty and trainees followed up on questions and got to know each other.

Members of the trainee group originally hailed from North America, Europe, Israel, and the Philippines. (All 20 are currently residing in either the United States, United Kingdom, Germany, or Sweden.) Among the 10 women and 10 men that composed the group were 11 MDs, 5 MD/PhDs, and 4 PhDs, all working on clinically oriented, laboratory-based projects. The faculty was a star-studded cast of hematology that included past and present editors of Blood and Hematologica, as well as past presidents of ASH and EHA. TRTH has had many notable faculty members since the program's inception. It was something of a surreal experience for a trainee to sit beside Cynthia Dunbar as she shared anecdotes from her years as editor-in-chief of Blood and war stories from her surgical rotation at the Massachusetts General Hospital when she was a medical student.

Our 7 o’clock breakfast on Sunday morning was accompanied by rain that transitioned to snow in the afternoon. The morning didactic sessions were followed by an introduction to small groups where our projects were constructively criticized, broken down, rebuilt, and broken down again in an effort to hone and focus our research goals. Each group consisted of five trainees and at least three faculty members. We spent time carefully and accurately identifying and redefining our hypotheses and aims. Two biostatisticians – Donna Neuberg and Emanuele Mazzola – circulated among the groups to provide insightful advice on experimental design. Over dinner that evening, David Bodine spoke passionately about the importance of mentorship (more about mentorship below).

While last year’s group was apparently able to enjoy breakfasts outside in the Villa’s beautiful quadrangle, our Monday morning was cold and snowy. Sessions on bone marrow failure syndromes, flow cytometry, and biostatistics transitioned to another afternoon of small-group work. As the workload intensified, some members the group light-heartedly suggested changing the design of the TRTH program to a “Survivor”-style format in which one trainee would be voted out of the Villa each day. But we were quickly reminded of our good fortune by Michaela Gruber who provided a reassuring and inspiring talk over dinner. Michaela was a trainee in the inaugural TRTH program four years ago, and she walked us through her “TRTHisation” process. She credits participation in the TRTH program as being instrumental in focusing her PhD thesis and helping her publish a manuscript in Blood, obtain fellowship support from EHA, and transition to a postdoctoral position at the Dana-Farber Cancer Institute.

Tuesday broke cool and clear as Bob Löwenberg, Editor-in-Chief of Blood, led the morning discussion on how to publish a scientific manuscript. After another small-group session, we boarded a bus to Milan to visit the monastery of Santa Maria delle Grazie, where having the privilege of viewing Leonardo da Vinci’s The Last Supper reminded us again that we were in a special place. The afternoon was spent walking into the Duomo and up the 250 stairs to the top of the Cathedral, exploring the beauties of downtown Milan, and enjoying Italian gelato. Over dinner that night, we amusingly recalled how often we had stored laboratory samples in the home freezer overnight but also reflected on how important it is to spend time each day with friends and family.

Wednesday’s didactic sessions were followed by a mock study section during which faculty introduced trainees to the process whereby grants are reviewed at the National Institutes of Health. “Don’t annoy the reviewer,” was among the critical pointers that were emphasized by the faculty who among them had decades of experience with the intricacies of the review process. As the small groups became more and more familiar with each other’s projects, general suggestions transitioned to more detailed discussions of experimental design and personal presentation style. Over dinner, 2013 TRTH Co-Chairs John Gribben and Hal Broxmeyer shared inspirational and insightful stories about their professional journeys. John and Hal have helped shape the organization and focus of the TRTH program since its inception and will be handing over the reins of leadership to new directors next year.

By Thursday, after spending five days and the better part of some nights together, a sense of comfort and camaraderie took over. Inside jokes and healthy competition between the small groups developed. Over dinner, the trainees and faculty revealed interesting facts in a game of “Two Truths and One Lie” between the main course and dessert. As part of that game, we tried to guess who among us completed half a dozen marathons in less than three hours and who once flew into the Bratislava airport thinking it was near Vienna!

Strictly limited to eight minutes, Friday’s final presentations were practiced and polished, with a clear emphasis on what had been modified. It was remarkable to see how the projects had developed during the week with input from peers and faculty. As the presentations came to an end, there was a small sense of relief that was quickly overwhelmed by a much larger disappointment that the week was over. It was time to get back to the lab and put into practice all of the week’s advice!

With the spring course and EHA annual conference behind us, we look forward to our next meeting in December at the ASH annual meeting in New Orleans both to hear updates of our projects and also to reunite with our new friends.

Mentorship in the TRTH Program

Mentorship was a standout focus of the TRTH spring course. Meals and coffee breaks provided the perfect venue for faculty and trainees to discuss personal and scientific questions, and precious free time was happily exchanged for first-hand advice. From aspects of career development to setting up xenotransplantation experiments, the faculty was dedicated to their roles as teachers and mentors, and these “hallway conversations” were among the highlights of the week. The course benefited from the different backgrounds and training stages of the participants, which brought together experienced postdocs with more junior trainees to share protocols and interpret experimental data.

Many Streams, Same Ocean: The Different Pathways to Translational Hematology in North America and Europe

One of the goals of TRTH is to bring together translational hematologists from around the globe. While TRTH is designed to establish lasting friendships and scientific collaborations, it is interesting to note some of the differences in training and career development between the American and European systems.

In North America, the most common path to becoming a hematologist starts with a four-year undergraduate degree, followed by four years of medical school, three years of internship and residency training, and three years of fellowship in a combined hematology and oncology program. One common deviation from this plan includes the Medical Scientist Training Program (MSTP), where one inserts a three- to five-year PhD program between the second and third years of medical school. And while the three-year fellowship is officially set up as 12 to18 months of clinical training followed by 18 to 24 months of research, the research experience is generally extended into a postdoctoral fellowship program that provides the time and resources to complete research projects begun during fellowship with a goal of becoming a principal investigator with an independent laboratory. These postdoctoral fellowships often last from four to six years during which one publishes papers and applies for mentored grants (usually NIH K08, K23, or K99/R00) designed to support the transition from senior post-doc to junior faculty member.

In Europe, there are key differences in career development, made even more complicated by differences in program design among individual countries. Most students enter into medical school (a six-year program) directly out of high school. Graduation from medical school is followed by specialization in internal medicine and then hematology, the specific course and duration of which varies from country to country. In Germany, for example, one applies to pursue training in hematology immediately after medical school. During the hematology specialty training, rotations in different departments ensure good general medical knowledge, though it is possible to find oneself able to confidently manage the work-up of a patient with newly diagnosed acute leukemia before being able to properly interpret an electrocardiogram. Other countries, such as the United Kingdom, integrate defined rotations in different internal medicine disciplines before beginning specialist training in hematology.

As opposed to the North American system, where almost all fellowships combine hematology with training in solid tumor oncology, it is much more common in Europe to train solely as a hematologist. This hematology-only training provides more extensive exposure to benign hematology, hematopathology, and transfusion and laboratory medicine. As for an academic postgraduate degree, the curriculum also varies among countries, with some countries integrating a doctoral thesis into medical school, and others offering a three- or four-year PhD degree program incorporated into the specialty training curriculum (usually after completing clinical training). As is evidenced by the number of European fellows doing postdoctoral fellowships in the United States, it is common to spend time abroad focusing on basic or translational science while free of clinical commitments.

The career endpoint may also be different. In the United States, the goal is often to become an independent investigator; on this path, one passes through a series of academic ranks that include assistant professor (non-tenured), associate professor (tenured), and professor. Usually the MD or MD/PhD scientist maintains a clinical commitment, though clinical responsibilities are typically limited to 20 percent effort such that 80 percent of the time is spent in the laboratory. (There is a joke among trainees that one can dedicate 100 percent to both clinical and laboratory pursuits by simply working twice as much!) As long as one is successful at obtaining research grant support, the clinical commitment generally involves seeing patients in clinic once a week (one half-day) and spending approximately four weeks a year in the hospital rounding on patients on the leukemia service or on the bone marrow transplant unit, and consulting on patients with benign hematologic abnormalities.

From the European perspective, the concept of “protected research time” is less well-developed, and physician-scientists will often have 50 percent or more of their time committed to clinical duties, including ward and shift work. While this time allocation keeps MDs in the clinic, it also makes it more difficult to advance a research project when so much of one’s effort is spent seeing patients. Consequently, experiments must be done after a full day of clinic or on weekends. In addition, many countries do not credit the research time toward hematology specialty requirements, further prolonging the training period.

In the United States, the National Institutes of Health provides grants both to individuals and to teams of individuals to pursue whatever research was outlined in the successful investigator-initiated application. In Europe, money is often awarded directly to a department or to a group, and the chair or group leader allocates the funds. Truly independent and tenure-track research positions in Europe are the exception rather than the rule, and eligibility criteria often exclude MDs because of their dual clinical and scientific commitments.

Though there is a clear need for translational research – research that ultimately has a direct impact on patients – the pathway to becoming an independent physician scientist is rife with uncertainty. Individually, TRTH trainees had somewhere between 12 and 20 years of postsecondary education, and despite this personal investment in education and the societal investment in us, we universally expressed concern over both research funding cuts and the ultimate availability of independent research positions. Nevertheless, trainees and mentors alike are carried by our enthusiasm and inspired by the possibility of making an impact on patient care. Many of us hope that TRTH has better positioned us for success and that we will be back one day as TRTH faculty members.

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