Every day, HHMI supports the pursuit of knowledge and the application of that knowledge to benefit humanity.W e have structured the Institute—physically, programmatically, philosophically—to empower the world’s finest scientists and educators. These individuals are also architects of discovery: shaping their laboratories and classrooms, guiding their teams, and conceiving the pioneering experiments that lead to innovations of lasting consequence.

howard hughes medical institute 2010 annual report

ARCHITECTS OF DISCOVERY from the president

Forty-nine years separated framework, which is taking ­processes that protect chromo- identification of the P“ hiladelphia literal form in the construction somal tips during replication.) chromosome” in patients with of a laboratory building to house More than bragging rights were at chronic myelogenous leukemia the KwaZulu-Natal Research stake in tackling such a complex from the 2009 Lasker Award Institute for Tuberculosis and structure: many antibiotics work ceremony honoring three scien- HIV (K-RITH) in Durban, by shutting down bacterial ribo- tists for their work in developing South Africa. Our 10-year com- somes. New drugs are desperately drugs that target the protein pro- mitment to K-RITH recognizes needed, and novel antibiotics duced by the aberrant gene. The that solutions to human needs based on Steitz’s discoveries are time span illustrates the complex- demand patience and time. now in development; two of the ity of transforming fundamental Patience and urgency are twin newest have the potential to treat biological knowledge—acquired poles that define a scientist’s life, drug-resistant infections like in many labs over many years— as HHMI investigator Jim Allison tuberculosis. We await the out- into therapies that are safe and well knows. Influenced by the come of further studies with the effective. And this is a success loss of family members to cancer, opposite of patience. story, due in part to research by he focused on immunology to Yet it’s perhaps no acci- Lasker awardees (and HHMI find more effective treatments. dent that, for 13 years, HHMI investigators) Brian Druker and This year, a drug built on a key benefited from the leadership Charles Sawyers. discovery made in Allison’s lab in of an historian trained to take The Howard Hughes Medical the 1990s became the basis for the long view: Hanna Holborn Institute, founded shortly before a promising treatment for late- Gray, a Renaissance scholar Peter Nowell and David Hunger­ stage melanoma. It also validates and ­academic leader. As Trustee ford named the chromosomal a novel approach for boosting the Chair, she demanded the best abnormality, is dedicated to dis- immune response to tumor cells. thinking on the Institute’s behalf, covery research in the biological X-ray crystallographer Tom balancing today’s urgent need sciences. We believe knowledge Steitz has patiently characterized with the patience to enable generated in our laboratories will complex biological molecules, ­discovery for decades to come. someday benefit humanity and and the ribosome—a vast molec- Thank you, Mrs. Gray. have created enabling structures ular machine that generates the that provide our scientists with proteins needed for cell func- the long-term freedom needed for tion—was an irresistible target. big research challenges. In 2009, he shared a Nobel Prize This year’s annual report for achieving that goal. (HHMI theme—“Architects of Discov- investigator Jack Szostak was ery”—speaks to that enabling also honored for illuminating the Robert Tjian, President essential philosophy behind a new 10 big stories cycle of science education grants, totaling $70 million, that will allow 50 universities across the Welcome to the 2010 Annual Report of country to test innovative ways of teaching science to under­graduate the Howard Hughes Medical Institute. and precollege students. Another This document provides a snapshot of our $9 million in grants will support 13 leading research scientists who activities for the year. For a detailed are committed to making science picture—including interviews, interactive more engaging to undergraduates. features, and a deeper look at many of the stories presented here—visit the full report online: www.hhmi.org/annualreport2010. We’d love to hear what you think.

foundation for the drug’s develop- ment 15 years ago when, at the University of California, Berkeley, he discovered the molecule and found a way to shut it down. 03 Schmoke Elected Chairman of the HHMI Trustees 01 Kurt L. Schmoke, dean of New Melanoma Drug the Howard University School Shows Promise of Law, was elected chairman of For the first time, a drug was the Trustees of HHMI. A distin- shown in a clinical trial to extend guished attorney and respected the lives of patients with stage advisor to a number of educa- III and IV melanoma. Called tional and other organizations, ­ipilimumab, the drug liberates the Schmoke has dedicated much immune system from a molecule 02 of his life to public service. In that usually reins it in, leaving T Transforming Science Education addition to academia, his career cells free to do an important job: at All Levels has included private practice, a attack tumors. Research by HHMI There’s no substitute for first- domestic policy position in the investigator Jim Allison set the hand discovery. That’s the Carter White House, and three

From the HHMI charter: The primary purpose and objective of the Howard Hughes Medical Institute shall be the promotion of human knowledge within the field of basic sciences (principally the field of medical research and education) and the effective application thereof for the benefit of mankind. terms as mayor of Baltimore, MD, HHMI investigator Elizabeth C. where he focused on improv- Engle identified the condition’s ing the city’s school system and genetic cause. Children with the economic development. Schmoke inherited disease, called congenital succeeds Hanna H. Gray, presi- fibrosis of the extraocular muscle dent emeritus of the University type 3, have drooping eyelids and of Chicago, who will continue to cannot move their eyes fully. Once serve as a Trustee. Engle, of Children’s Hospital Boston, and her colleagues identi- fied 29 families with the disorder, they were able to link it to a gene encoding a protein that helps neurons navigate a developing 05 nervous system and connect with Our Biased Genes the appropriate cells. With support from an HHMI jian: James Kegley James T jian: Collaborative Innovation Award, HHMI investigator Catherine Dulac and a team of researchers revealed how genetic contribu- tions from mom or dad affect an offspring’s behavior. The pposite side, O pposite side, aul Fetters ambitious new analysis in mice demonstrated that for more than 04 1,300 genes active in the brain, Evolution’s Art there is a significant bias as to The rainbow of colors and pat- which copy is active—the one terns that decorate the animal inherited from the mother or the

att Kalinowski Kalinowski M att C arroll 05: and S ean B. S higeyuki Koshikawa, erner, one that came from the father.

W kingdom remains one of nature’s most awesome mysteries. With two 07 T homas papers that describe the evolution of spots and color changes in fruit Bishai Named Head of New flies, Sean B. Carroll strength- TB-HIV Institute ened the notion that ­evolution Physician and renowned tubercu- aul Fetters 04: 04: aul Fetters tends to tinker with existing losis researcher William R. Bishai genetic machinery to arrive at was named the first full-time new patterns and forms. Carroll, director of the KwaZulu-Natal

arper 03: P om H arper 03: an HHMI investigator at the Research Institute for Tuber- T University of Wisconsin–Madison, culosis and HIV (K-RITH), a has spent his career studying the collaboration between HHMI and 10: P © HHMI 10: / PR N ewswire, L iz Baylen S awyers: Valls; D ruker: John 09: aul Fetters genetic underpinnings of evolu- the University of KwaZulu-Natal tion and development, identifying in Durban, South Africa. At the the molecular mechanisms that 06 Johns Hopkins University, Bishai’s The Molecular Origins of aul Fetters 08: P 08: aul Fetters lead to new traits and species. He research has focused on under- is also an award-winning author a Rare Eye Disorder standing how the tuberculosis and educator; in 2010, he was After a search across five conti- bacillus is so successful at infect- named vice president for science nents for children with a rare eye ing humans. His first priority as education at HHMI, succeeding movement disorder, a large interna- K-RITH director will be to recruit Peter J. Bruns. tional team of collaborators led by an international cadre of 07: P © HHMI 07: L utterodt / PR N ewswire, E vans- Kaye 06: 02: L ibraryNIH 02: N ational D onald Bliss and S riram of M edicine, S ubramaniam, 01: scientists and clinicians with the work that revolutionized treatment long-term goal of controlling the of the once-incurable disease. devastating coepidemic of tuber- culosis and HIV.

09 10 Druker, Sawyers Receive Genetic Stutter Can Lead to ALS Lasker Award Starting with two simple Decades of deeply collaborative experimental systems—yeast 08 work that no single lab could and flies—HHMI investigator Nobels Honor Szostak, Steitz have accomplished alone led to Nancy M. Bonini and col- HHMI investigators Thomas A. development of the first treat- leagues discovered one of the Steitz and Jack W. Szostak were ment that selectively targets an most common genetic risk awarded Nobel Prizes in 2009. enzyme that causes cancer. In ­factors identified to date for the Steitz, of Yale University, shared 2009, the three lead researchers neurodegenerative disease amyo- the Chemistry award with received the Lasker-DeBakey trophic lateral sclerosis (ALS), ­Venkatraman Ramakrishnan Clinical Medical Research also known as Lou Gehrig’s of the Medical Research Council Award. Presented to HHMI disease. In about 5 percent of Laboratory of Molecular Biol- investigator Charles L. Sawyers ALS patients, a genetic stutter ogy and Ada E. Yonath of the of Memorial Sloan-Kettering produces too many copies of a Weizmann Institute of Science Cancer Center, HHMI investiga- short segment of DNA in a gene for research that showed, with tor Brian J. Druker of Oregon called ataxin-2, the University of x-ray crystallography and a Health & Science University, and Pennsylvania team found. The host of other techniques, what Nicholas B. Lydon, formerly of mutation appears to contribute the ribosome looks like and Novartis, the award recognized to the protein clumping that how it functions at the atomic their development of novel drugs interferes with the normal func- level. Szostak, of Massachusetts for chronic myeloid leukemia, tion of motor neurons. General Hospital and Harvard Medical School, shared the Physiology or Medicine prize with Elizabeth Blackburn of the University of California, San Francisco, and Carol Greider To view the full of the Johns Hopkins University School of Medicine, for discov- ering how chromosomes are report, please visit: protected by telomeres and the enzyme telomerase. The work www.hhmi.org/ has revealed how organisms rely on telomerase to protect their genome from degradation. annualreport2010 The Howard Hughes Medical grants and investment manage- financial highlights Institute is the nation’s largest ment expenses. The endowment is private supporter of academic the Institute’s principal source of biomedical research. Classified funding. The investment objective as a medical research organiza- is to manage the endowment in a tion by the Internal Revenue prudent manner that will main- Service, the Institute is required tain its purchasing power and will to spend at least 3.5 percent of its fund the Institute’s research and endowment each year on direct grants programs in perpetuity. On medical research activities and August 31, 2010, the endowment related overhead, exclusive of was approximately $14.8 billion.

Disbursements ($ in millions) 9 1 8 1 3 6 8 64 8 $8 2 7 7 $ 7 $ $ $ Lab Construction & Other Science Education Scientic Research 06 07 08 09 10

Endowment Allocations

9% 14%

14% 13% Domestic equity Market neutral arbitrage Bonds Distressed and credit sensitive Private equity 16% International equity 21% Hedged equity 1% Real assets 12%

Endowment ($ in millions) 2 9 0 6 9 7 2 , 4 6 3 8 , , 7 7 1 6 9 1 $ , 1 $ 3 $ 1 $14,765 $

06 07 08 09 10

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