NATIONAL INSTITUTES OF HEALTH • OFFICE OF THE DIRECTOR | VOLUME 29 ISSUE 2 • MARCH-APRIL 2021 Annals of NIH History: The 1918 Flu and COVID-19: A Tale of Two From Yellow Berets Pandemics to Nobel Laureates BY EIMEAR HOLTON, NIAID BY ETHAN SMITH, NINR It may seem like a coincidence that Nobel laureates Michael Brown, Joseph Goldstein, Harold Varmus, and Robert Lefkowitz all started their training at NIH in the summer of 1968. But it wasn’t just happenstance, according to Raymond Greenberg, a professor at the University of Texas Health Center at Houston (Houston) and author of Medal Winners: How the Vietnam War Launched Nobel Careers. His book tells this overlooked story through the lives of those four men. As the United States’ involvement in Vietnam escalated in the late 1960s, a doctor draft ensured an adequate supply of freshly trained physicians for the armed forces. “If you were a male physician, you were subject to a special NIAID CREDIT: draft for physicians,” said Greenberg Colorized scanning electron micrograph of a cell (blue) heavily infected with SARS-CoV-2 virus particles (red), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. during a virtual lecture he gave at NIH in November 2020. “Pretty much everyone The COVID-19 pandemic is not our first rodeo with battling a deadly was going to serve for some period of time.” virus, and it likely won’t be our last. As we continue to process the past year, Not all of the drafted physicians served the juxtaposition of COVID-19 pandemic and the influenza pandemic of 1918 in the combat zone of Vietnam; some were puts today’s challenges into perspective. Two prominent NIH scientists shared posted to U.S. military hospitals around their perspectives (virtually) at the January 12, 2021, launch of the Demystifying the world. But with public opinion of the CONTINUED ON PAGE 12 war deteriorating, many physicians sought alternative types of public service to satisfy CONTENTS their draft obligation. FEATURES • |1| The 1918 Flu and COVID-19 |5| Fueling the Next Genomics Revolution |10| COVID-19 Timeline (January–February) |14| Introducing NIH’s Newest Lasker Scholars Yellow Berets. One such alternative |18| Stadtman Investigators Pursuing Their Passion for Science was NIH’s Associate Training Program DEPARTMENTS • |1, 7| NIH History: From Yellow Berets to Nobel Laureates; My Adventures as (ATP), a two-year research program under an NIH Yellow Beret |2| DDIR: How the IRP is Fighting COVID-19 |3| Abbreviations the Commissioned Corps of the United |4| Training: Becoming a Resilient Scientist |8, 13, 17| Research Briefs |24| Photographic CONTINUED ON PAGE 6 Moment: A Visit From the New President FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH How the NIH Intramural Program Is Fighting the COVID-19 Pandemic BY MICHAEL GOTTESMAN, DDIR Given the constant presence of Currently, there are 23 institutes and Intramural Targeted Anti-COVID-19, NIH leaders such as NIH Director centers involved in COVID research a competition overseen by Ted Pierson Francis Collins and National with about 400 active projects— in NIAID. Of 159 applications, 40 were Institute of Allergy and Infectious ranging from basic science to preclinical funded. Diseases (NIAID) Director Anthony research to clinical trials—and 313 There have been so many important Fauci in the popular press, on distinct PIs. The research areas are intramural contributions to the TV and radio and in print, and in equally divided between immunology– COVID-19 effort that it is difficult commentaries in academic journals, host response and therapeutic to choose just a few to highlight in it is clear that the NIH has played (drugs and biologics) at 14%; 10% this essay, but I will do my best (and I a major role in strategic planning, in pathogenesis; 8% in genetics and hope that the architects of the equally communication of public-health genomics; and 7% in structural biology. important work that is not cited do not requirements, and development of Bioinformatics, virology, computational feel slighted). strategies to prevent, detect, and and systems biology, diagnostics, The most obvious is the contribution treat infection caused by severe acute epidemiology, and vaccines are all in of the dedicated team at NIAID’s respiratory syndrome virus Vaccine Research Center 2 (SARS-CoV-2), the virus There have been so many (VRC) to the development responsible for COVID-19. of a structure-based vaccine. What may not be as clear to important intramural contributions Since the SARS outbreak in many intramural staff are to the COVID-19 effort that it is 2002–2004, VRC Deputy the major contributions that Director Barney Graham and have been made over the difficult to choose just a few to his many talented associates past year by intramural— highlight in this essay. and colleagues, including and extramural—scientists, Kizzmekia Corbett, (NIAID), working in teams and as have been working on the independent contributors, general principles for creating to the science underlying our the 6% range. Natural history, clinical vaccines to counteract significant current understanding of the trial, and mental and behavioral health coronavirus epidemics. Targeting the diagnosis, prevention, therapy, and are in the 2–5% range. There are 63 coronavirus spike (S) protein, they pathophysiology of COVID-19. reagents available in the registry. discovered (with their collaborator Early in the COVID-19 Many of these research activities Jason McLellan, an alumnus of the pandemic, we sought to document were highlighted in the October VRC and now at the University of the contributions of our intramural 29–30, 2021, workshop organized Texas at Austin), that substitutions of scientists to the antipandemic effort by the NIH COVID-19 Scientific two prolines between two key areas by creating a dashboard in collaboration Interest Group (chaired by Pam would stabilize the S protein in its with Christine Cutillo (National Schwartzberg, NIAID) and colleagues native functional conformation. This Center for Advancing Translational at the FDA. In addition, the Office engineered structure has become the Sciences, NCATS) listing all of the of Intramural Research, with funding basis for many of the vaccines under projects being carried out in the by NIAID, provided grant support current development, all of which have intramural research program (IRP). for intramural scientists as part of the proven to be exceptionally effective in 2 THE NIH CATALYST MARCH–APRIL 2021 NIH ABBREVIATIONS FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH CBER: Center for Biologics Evaluation and Research, FDA CC: NIH Clinical Center CCR: Center for Cancer Research, NCI CIT: Center for Information Technology DCEG: Division of Cancer Epidemiology and Genetics, NCI DIPHR: Division of Intramural Population Health Research, NICHD FAES: Foundation for Advanced Education in the Sciences FARE: Fellows Award for Research Excellence FelCom: Fellows Committee FDA: Food and Drug Administration preventing SARS-CoV-2 symptomatic in SARS-CoV-2 is modulated by mucin FNIH: Foundation for the NIH Frederick National Laboratory infections. Specifically, this variant is type O glycosylation, which possibly FNL: IRP: Intramural Research Program encoded by the messenger RNA present explains why the UK B.1.1.7 variant HHS: U.S. Department of Health in the Pfizer and Moderna vaccines. It is more transmissible than the other and Human Services NCATS: National Center for Advancing is also encoded by the adenovirus type variants, because some of the mutations Translational Sciences 26 vaccine vector in the Johnson and in this variant are close to this site. At NCBI: National Center for Biotechnology Johnson–Janssen vaccine. the other end of the viral replication Information NCCIH: National Center for Complementary In the area of therapeutics, NCATS cycle, Nihal Altan-Bonnet (National and Integrative Health has done extensive work to screen Heart, Lung, and Blood Institute) NCI: National Cancer Institute existing drugs to be repurposed for demonstrated that SARS-CoV-2 uses NEI: National Eye Institute NHGRI: National Human Genome treatment of SARS-CoV-2 infection. a lysosomal pathway to leave cells, an Research Institute In addition, the team of Emmie unexpected finding that could have NHLBI: National Heart, Lung, and Blood Institute de Wit and Vincent Munster at important therapeutic implications. NIA: National Institute on Aging NIAID’s Rocky Mountain Laboratories Considerable progress has also NIAAA: National Institute on Alcohol (Hamilton, Montana) was one of the been made in understanding what Abuse and Alcoholism NIAID: National Institute of Allergy first to demonstrate the efficacy of the host factors predispose someone to and Infectious Diseases antiviral agent remdesivir in rodents severe disease. Helen Su and Luigi NIAMS: National Institute of Arthritis and Musculoskeletal and Skin Diseases and nonhuman primates. Their work Notarangelo, NIAID, in collaboration NIBIB: National Institute of Biomedical accelerated the development of this with the laboratory of Jean-Laurent Imaging and Bioengineering agent for treatment of hospitalized Casanova at Rockefeller University NICHD: Eunice Kennedy Shriver National Institute of Child Health and patients with moderate to severe (New York), showed that in up to 15% Human Development COVID-19; remdesivir remains a of persons severely ill with COVID- NIDA: National Institute on Drug Abuse NIDCD: National Institute on Deafness standard