From the President

Forty-nine years separated identification of the “Philadelphia chromosome” in patients with chronic myelogenous leukemia from the 2009 Lasker Award ceremony honoring three scientists for their work in developing drugs that target the protein produced by the aberrant gene.

The time span illustrates the complexity of transforming fundamental biological knowledge—acquired in many labs over many years—into therapies that are safe and effective. And this is a success story, due in part to research by Lasker awardees (and HHMI investigators) Brian Druker and Charles Sawyers.

The Howard Hughes Medical Institute, founded shortly before Peter Nowell and David Hungerford named the chromosomal abnormality, is dedicated to discovery research in the biological sciences. We believe knowledge generated in our laboratories will someday benefit humanity and have created enabling structures that provide our scientists with the long-term freedom needed for big research challenges.

This year’s annual report theme—“Architects of Discovery”—speaks to that enabling framework, which is taking literal form in the construction of a laboratory building to house the KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH) in Durban, South Africa. Our 10-year commitment to K-RITH recognizes that solutions to human needs demand patience and time.

Patience and urgency are twin poles that define a scientist’s life, as HHMI investigator Jim Allison well knows. Influenced by the loss of family members to cancer, he focused on immunology to find more effective treatments. This year, a drug built on a key discovery made in Allison’s lab in the 1990s became the basis for a promising treatment for late-stage melanoma. It also validates a novel approach for boosting the immune response to tumor cells.

X-ray crystallographer Tom Steitz has patiently characterized complex biological molecules, and the ribosome—a vast molecular machine that generates the proteins needed for cell function—was an irresistible target. In 2009, he shared a Nobel Prize for achieving that goal. (HHMI investigator Jack Szostak was also honored for illuminating the processes that protect chromosomal tips during replication.) More than bragging rights were at stake in tackling such a complex structure: many antibiotics work by shutting down bacterial ribosomes. New drugs are desperately needed, and novel antibiotics based on Steitz’s discoveries are now in development; two of the newest have the potential to treat drug-resistant infections like tuberculosis. We await the outcome of further studies with the opposite of patience.

Yet it’s perhaps no accident that, for 13 years, HHMI benefited from the leadership of an historian trained to take the long view: Hanna Holborn Gray, a Renaissance scholar and academic leader. As Trustee Chair, she demanded the best thinking on the Institute’s behalf, balancing today’s urgent need with the patience to enable discovery for decades to come. Thank you, Mrs. Gray.

Robert Tjian, President

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