NATIONAL INSTITUTES OF HEALTH • OFFICE OF THE DIRECTOR | VOLUME 22 ISSUE 1 • JANUARY-FEBRUARY 2014 Crowdsourcing The Festival That Amost Wasn’t Accelerates Toxicity Testing Report From the 2013 Research Festival BY JENNIFER SARGENT, NIAMS BY LESLEY EARL, NCI Scientists at the National Institute Neither snow, nor rain, nor for Environmental Health Sciences the gloom of a government shut- (NIEHS) have turned to crowdsourcing to down could keep NIH’s Research help analyze massive datasets and develop Festival from happening. It was just new models to predict the toxicity of phar- postponed a little. macological and environmental chemicals. Led by co-chairs Dan Kastner, Crowdsourcing involves using collective the scientific director of the National intelligence to answer a problem. The idea Human Genome Research Institute is that many hands make light work—or, in (NHGRI), and Luigi Ferrucci, the this case, that many heads make for more scientific director of the National efficient problem solving. And what better Institute on Aging (NIA), the festival way to get a scientific crowd together to served up a feast of basic science and tackle a problem than to issue a challenge? translational medicine. DARRYL LEJA, NHGRIDARRYL It might even be right for your project. Although the festival was origi- Crowdsourcing initiatives “get the best nally scheduled for early October, the and the brightest contributing their knowl- 16-day government shutdown forced edge to get the best result,” said NIEHS the organizers to rapidly reschedule Deputy Director Rick Woychik, who helps the events for November 6 to 8 steer NIH policy for big-data challenges. instead. Most of the planned events This design represents the two 60th anniversary celebrations that In 2013, scientists at NIEHS, the took place—including the plenary the 2013 Research Festival recognized: that of the NIH Clinical Center, which opened in July 1953; and of James Watson and Francis Crick’s National Center for Advancing Transla- session, many concurrent symposia, landmark paper that first described the DNA double-helix structure, tional Sciences (NCATS), the University of and a much-anticipated Scientific published in Nature on April 25, 1953. North Carolina (UNC; Chapel Hill, N.C.), Directors Poster Session and Cook- and two nonprofits—DREAM (Dialogue off—but the Vendor Tent Show had to be rescheduled for the spring, and the National for Reverse Engineering Assessments and Graduate Student Research Conference had to be cancelled. Methods) and Sage Bionetworks (Seattle, “The silver lining, perhaps, of the shutdown was that NIH emerged as one of a very Wash.)—partnered to launch a Toxicoge- short list of government activities that everybody agreed has incredible value,” said NIH netics Challenge that asked participants to Director Francis Collins in his opening remarks at the plenary session. use genetic and cytotoxic data to develop CONTINUED ON PAGE 8 algorithms to predict the toxicity of differ- ent chemicals. Analyses such as these are CONTENTS aimed at understanding why different people FEATURES • |1| Crowdsourcing: Accelerates Toxicity Testing |1| 2013 Research Festival exposed to the same chemical in the same |3| Precision Medicine: Louis Staudt |6| Bill Gates at NIH |14| Obituaries environment display different reactions. DEPARTMENTS • |2| Guest Editorial: NIH Clinical Research Is Changing the Trajectory of Care 4| Training Page: Career Advice |5| Abbreviations |7| SIG Beat |16| Colleagues: Recently CONTINUED ON PAGE 5 Tenured |18| Announcements |20| Photographic Moment: Doing It Right (Radiation Safety) GUEST EDITORIAL FROM THE DEPUTY DIRECTOR FOR INTRAMURAL CLINICAL RESEARCH The NIH Intramural Clinical Research Program: Changing the Trajectory of Care BY STEVEN HOLLAND Deputy Director for Intramural The eruption of excitement around Perhaps our greatest area of shining Research Michael Gottesman recently the dramatic and successful treatments of success is one that has been a jewel in our reviewed the profound effects that the cancer with chimeric antigen receptors has diadem for decades: our unique capacity as a NIH intramural research program (IRP) finally persuaded even the long-standing community of like-minded investigators to has wrought over the years on the current skeptics that immune control of cancer is identify specific patient phenotypes; recruit conduct of general medicine, including the real, harnessable, and effective. The deep similar patients and their families; bring use of automated blood-cell counting, vac- intramural commitment to the immune them in for study; genotype them; under- cine development, coronary imaging, pro- control of cancer by Steve Rosenberg’s lab stand the underlying mechanisms; and— tection of the blood supply, and genomic (NCI), exploring cell-mediated mechanisms, with hard work and good luck—develop new analysis. and Ira Pastan’s lab (NCI), using humoral therapies. For example, the extraordinary Following up, I wanted to highlight ones, both anticipated and facilitated this work of Marston Linehan’s group (NCI) in some ongoing intramural approaches and development. This effort to focus, train, and dissecting and defining the metabolic basis trials at the Clinical Center that promise release the latent powers of immunity on of kidney cancers has changed diagnosis, to change understanding and practice in specific tumors has emerged as one of the screening, therapy, and survival. the future. most critical and important ways in which The list of new diseases (and their genes) The treatment of patients with severe we will address cancer in the future. discovered at NIH stretches way back, but illness is special. There is a lot of anguish, Development of new tools is essential, of the pace of discovery in the past few years a lot of anxiety, and often a lot of death. It course. But just as critical is learning how to has been breathtaking: novel autoinflam- takes a special and invested commitment use the tools that already exist. Lou Staudt’s matory diseases (DIRA, NOMID); novel from all involved—patients, nurses, doctors, group (NCI) has dissected the molecular immunodeficiencies (DOCK8, PLCG2, scientists, administrators, and directors—to signature and definition of lymphomas, VPS45); novel endocrinopathies (ARMC5, sustain the conviction, momentum, and sup- enabling their detection and tailoring of NT5E, EHHADH); novel metabolic syn- port necessary to carry us through the times treatments. Staudt, Kieron Dunleavy dromes (Proteus); novel cancer syndromes that are inevitably trying and painful. But (NCI), Wyndham Wilson (NCI), and (HIF2A, GATA2); and the remarkable yield if this is where the battle lines are drawn, colleagues have honed the chemotherapy of the Undiagnosed Diseases Program led by dare we walk away? of lymphoma to a fine edge, using the NIH- Bill Gahl. All these new diseases and genes The successes of antiretroviral therapy established principles of multiagent chemo- provide even more targets for the massed for human immunodeficiency virus (HIV) therapy to achieve terrific cure rates while investigative power of NCATS, promising started at NIH originally with zidovudine reducing the need for more toxic therapies. even more new drugs for the future. (AZT); was perfected over the years with In the infectious-disease realm: While And then there’s the Julie Segre’s team infection prophylaxis, multidrug combi- working to create new drugs for tubercu- (NHGRI), which championed genome nations, and simplified delivery; and has losis, Clif Barry’s lab (NIAID) has shown sequencing to track a microbe’s spread. culminated in a widespread group of drug how to use the old drug linezolid to success- This essay presents a very brief, neces- targets and the cognate drugs that have given fully treat multidrug-resistant tuberculosis. sarily inadequate, and incomplete sampler us a new paradigm for how serious diseases Cindy Dunbar’s group (NHLBI) turned of some of the many things that are ongo- can be turned. The unconquered frontiers of eltrombopag, a drug used for severe throm- ing and outstanding in the Clinical Center’s immune reconstitution and HIV-associated bocytopenia, into a drug that can rescue intramural clinical program. What we have malignancies are slowly yielding through a significant number of people who have changed about the practice of medicine so innovative IRP studies. severe aplastic anemia. far is only the prologue. 2 THE NIH CATALYST JANUARY-FEBRUARY 2014 FEATURE Precision Medicine Using Genomics to Get Patients the Right Treatment BY CHRIS PALMER, NCI More than a decade and about aggressive subtype, three billion dollars were sunk into resulting in inad- sequencing the first human genome. Now, equate treatment. that feat can be accomplished in as little as Molecular tools, five days and runs about $4,000. The pro- however, can easily cess is getting quicker and cheaper by the distinguish these day. This reduction in the time and cost of subtypes so patients genomic sequencing is the foundation of can be treated personalized medicine in which genetic appropriately. “The analysis may point to the most effective current ways that RICHFOLKERS, NCI treatments. we’re diagnosing “This is a particularly exciting time for cancer and treating us because we have tools that are just jaw- cancer are chang- dropping in their power to examine the ing before our eyes,” human genome,” Louis Staudt told the said Staudt. “We’re Louis Staudt, the director of NCI’s Center for Cancer Genomics, described how molecular audience that