Fostering Communication and Collaboration The nihCatalyst A Publication for NIH Intramural Scientists National Institutes of Health bOffice of the Director' e Volume 11, Issue 6* November-December 2003 CC Celebrates 50th at Research Festival > the Sum of the Parts Giants Standing Copeland and Jenkins On the Shoulders of Giants And the Development Of Mouse Cancer Genetics by Fran Pollner DeVita it by PeterJ. Kozel ince put this way: “It’s nice V to come home.” And in one way or an- other, each of the speak- ers who took the stage to commemorate the CC’s 50th anniversary ex- pressed an affection for the daily working envi- ronment at NIFI and its research hospital that Bill Branson conjured up the image of CC DirectorJohn Gallin salutes former and current NIH NancyJenkins Neal Copeland home: scientists and a half-century of transforming research t’s hard to say what the NIH sci- The collaborative entific directors were honoring and feisty spirit among colleagues remi- The perseverance, warmth, and mu- I when they picked husband-and- niscent of the best kind of sibling cama- tual regard that characterized the rela- wife cancer genetics investigators raderie—and squabbling tionships between the physician-re- Neal Copeland and Nancy Jenkins searchers and the patients undergoing to present this year’s Mider Lecture. experimental treatments, sometimes ex- Was it their legacy—almost 700 pa- tending through decades of follow-up pers and the reference mouse ge- The culture of NIFf, like that in a nome map? Was it their astonishing nurturing family, that supported the pur- record of training successful scien- suit of new ideas and personal intellec- tists? Was it their innovative “recom- tual expansion bineering” technique that’s revolu- They all saw the past—studded with tionizing the manipulation of DNA? the gems of biomedical research that Or was it their almost unparalleled, contributed enormously to science and highly productive collaboration, now human health—as prologue to the fu- in its third decade? ture. capsules continue on page 3 The NIH Catalyst spoke with Copeland chief se- and Jenkins— and CONTENTS nior investigator, respectively, of the Bill Branson 1 7 NCI-Freclerick Mouse Cancer Genet- Back in the Day: Former NCI director Giant Shoulders: CC ProtoType: Crafting ics Program shortly before they Vince DeVita displays the senior — faculty Celebrates 50th Clinical Protocols taught a short course on mouse ge- of the NCI Medicine Branch, circa 1975: netics at the Jackson Laboratory in (left to right) George Canellos (now at Copeland & Jenkins 10-15 Research Cornucopia: Bar Harbor, Maine, this past summer. Haward), Bruce Chabner (Massachu- & Recombineering An IRP Year’s Worth setts General Hospital), Phil Schein Jenkins and Copeland met in 1977 2 (University Pennsylvania), DeVita as postdoctoral fellows in Geoffrey of From the DDIR: 16-17 (“with more hair and polyester"), and Cooper’s retrovirus laboratory at the A 50-Year Bonanza Recently Tenured Bob Young (Fox-Chase Cancer Center). Of CC Research Dana Farber Cancer Institute in Bos- 18-19 DeVita 's talk, not only tracked the rise of ton. 4-7 At the time, retroviruses were chemotherapy and the decline in cancer Catalytic Reactions/ Research Festival Relay Revelry/Training at the “very forefront of molecular modality, it was a paean to dozens of The Clever Host biology,” according to Jenkins. “Mo- his NCI colleagues and the Friday Gene Complexities 20 continued on page 8 afternoon Society ofJabbering Idiots A Random Sample At Your Fingertips The NIH Catalyst From the Deputy Director for Intramural Research Highways and Byways: 50 Years of Research at the Clinical Center his year we celebrate the 50th anniversary of like driving a car at night. You can only see as far as the opening of the NIH Clinical Center. On the headlights, but you make the whole trip that way.” T October 14, 2003, a symposium was held in The history of the Clinical Center has many ex- Masur Auditorium to recognize the scope and depth amples of circuitous trips without maps that have of research accomplishments that represent some of arrived at unexpected and far-reaching destinations. the history of the Clinical Center. For example, studies of the rare human embryonic Those who attended—whether newcomers to NIH cancer choriocarcinoma, by Roy Hertz and Min Chiu or longtimers who were here when the doors to the Li, led to a need to follow success of treatment by Clinical Center first opened—could not help but be measuring human chorionic gonadotropin. Judy impressed by the enormous impact the Clinical Cen- Vaitukaitus developed the first radioimmunoassay for Michael Gottesman ter has had on the practice of medicine, from devel- this hormone—-and this assay became the basis for oping the current paradigm for the chemotherapy of the home pregnancy test, which, needless to say, cancer, to changing the way in which ischemic heart has had profound social consequences. disease is treated, to creating new approaches to the Tom Waldmann, in searching for a way to diag- treatment of multiple sclerosis. nose and treat a rare form of T-cell leukemia, devel- This kind of occasion also inspires reflection on oped an anti-TAC antibody to the a-chain of the the constellation of causes of past success to assist interleukin-2 receptor. This antibody blocks T-cell us in imagining how best to ensure continued suc- activation and has found important use in the treat- cess in the future. ment of several autoimmune dis- In listening to the presentations orders at the Clinical Center, includ- and reviewing other contributions To paraphrase the ing multiple sclerosis and autoim- made at the Clinical Center, I was mune uveitis. struck by the fact that some of the NOVELIST E.L. Finally, our courageous patient major paradigm-shifting research Doctorow: Re- volunteers and the observations was accomplished in the face of made by astute clinicians have led great resistance and with enormous search ‘is like driv- to new pathways to discovery. The investment of time, staff, and re- ing a CAR AT NIGHT. combined observations of Isaac sources. Asimov and Dr. Seuss summarize In keeping with the current road You CAN ONLY SEE AS the NIH research terrain. Asimov map metaphor, Clinical Center re- FAR AS THE HEAD- put it this way: "The most exciting search built the major highways, phrase to hear in science, the one bridges, and tunnels that have LIGHTS, BUT YOU that heralds new discoveries, is not transformed the face of medicine. Eureka!, but Hmm, that's funny." MAKE THE WHOLE TRIP Vince DeVita’s recounting of the And from Dr. Seuss, we append a need for protracted persuasion of THAT WAY.’ key road map legend: "From there influential skeptics in the develop- to here, and here to there, funny ment of multiagent chemotherapy things are everywhere." We need of cancer—and the involvement of so many physi- to continue to be accessible to patients with a large cians and patients over so many years—illustrates variety of disorders, and observe them carefully as the kind of major effort to which I am referring. we care for them, to learn more about human health Similarly huge efforts informed NIH contributions and disease. to cardiac surgery (the first implantation of an artifi- We are awaiting the imminent recommendations cial mitral valve), to the treatment of manic-depres- of a Blue Ribbon Panel on Clinical Research at the sive illness (demonstration of the dramatic effect of NIH, co-chaired by Ed Benz, president of the Dana- lithium), and to identification and control of HIV in- Farber Cancer Center in Boston, and Joe Goldstein, fection. professor at the University of Texas Southwestern So, too, will current and future undertakings re- Medical Center, Dallas, on how best to ensure that lated to major public-health problems require a large the new Clinical Research Center has as much im- commitment of resources and energy. The payoff, pact as the Clinical Center has had in the past. however, is certainly larger. We are now in the pro- I am confident that NIH will be asked to continue cess of planning a major initiative to better under- to take on important public health issues—but not stand the physiological causes and consequences of eschew the rare diseases that have led to so many obesity, an effort that will require a substantial trans- important insights about human pathophysiology. NIH commitment. If you are interested in watching and listening to But the success of clinical research at NIH is as the many outstanding presentations given at the Clini- much written in the shortcuts and scenic byways as cal Center 50th anniversary symposium, they are in its major highways. When we study rare diseases, archived at <http://www.cc.nih.gov/50th/>, as are we never know at the outset where research will the special 50th-anniversary series of Clinical Center take us, but the results are invariably useful and fre- Grand Rounds. quently have profound effects on human health. To —Michael Gottesman paraphrase the novelist E.L. Doctorow: Research “is Deputy Directorfor Intramural Research 2 — November-December 2003 photos by Bill Branson CC Celebrates 50th at Research Festival Giants Standing on the Shoulders of Giants text by Fran Pollner Francis Collins, director, NHGR1 (at NIH since 1993) What’s next after you 've mapped the human genome? a human haplotype map to chart the variants that contribute to common diseases—an international project involving six countries and support from 18 NIH institutes Harvey Alter, chief CC Infectious Diseases Section (at NIH since 1969); Co-discoverer of the Australia antigen, Elizabeth Nabel, scien- eradicator ofposttransfusion hepatitis, tific directorfor clinical and poet: “When I came to NIH as a Eugene Braunwald, Hersey research, NHLBI (at NIH lowly fellow, 1 saw that patients were distinguished professor medicine.