As the United States pauses to observe the 10th anniversary of the September 11th terrorist attacks, we reflect on the research advances that contribute to new counterterrorism measures—understanding anthrax, for example—and the health of our soldiers in Iraq and Afghanistan, including under-studied conditions such as traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Here are a few examples, and these only cover discoveries made at Sanford-Burnham since September 11, 2001. Can you think of more? Please share your thoughts in the comments below.
2001: On the heels of an anthrax attack that killed five people, Dr. Robert Liddington and colleagues solve the crystal structure of the anthrax lethal factor, one of two toxins secreted by the deadly bacteria. The finding gives scientists a blueprint for the toxin’s undoing.
2004: Dr. Robert Liddington and colleagues solve the crystal structure of the binding complex between anthrax toxin and the molecule it uses to bind to human tissues. The study offers new leads for the discovery of anthrax antitoxins that could be used in conjunction with antibiotics to treat late-stage anthrax.
2005: Drs. Maurizio Pellecchia, Robert Liddington, Alex Strongin, Jeffrey Smith, and colleagues discover chemical inhibitors that neutralize the anthrax lethal factor. These inhibitors represent a significant advance in developing a possible emergency treatment for anthrax.
Discovering radiation countermeasures
2004-2005: Drs. Maurizio Pellecchia, John Reed, and colleagues develop chemical inhibitors of Bid, cell death gene product induced by radiation. These chemicals promote the survival of irradiated cells and improve survival in animal models of lethal radiation injury.
2008: Drs. Maurizio Pellecchia, Ze’ev Ronai, and collaborators develop chemical inhibitors of JIP and JNK, proteins that stimulate a cell death program following radiation. The chemicals protect against radiation-induced cell death and prolong survival in animal models of lethal radiation injury.
Improving military health in Iraq and Afghanistan
2008: Dr. John Reed and colleagues discover naturally occurring mechanisms that protect the brain against PTSD and psychological stress, thus revealing novel targets for drug discovery. (The genes responsible for this protection from psychological stress were first discovered by Dr. Reed’s laboratory in 1995 and 1998.)
2009: Dr. Andrei Osterman and colleagues develop prototype antibiotics for resistant bacteria associated with wound infections, including Iraqibacter.
2011: Drs. John Reed, Maurizio Pellecchia, and colleagues discover a prototype drug that reduces PTSD symptoms in animal model.
2011: Drs. John Reed, Stuart Lipton, Yu Yamaguchi, and their teams discover that a naturally occurring, brain-protecting gene called BI-1 (previously discovered by Dr. Reed’s Sanford-Burnham research team in 1998) reduces TBI, thus providing a potential new target for drug discovery.
Looking ahead at the next 10 years
Drs. Stan Krajewski, Maryla Krajewska, and John Reed have discovered the culprit enzyme (called Caspase-8) responsible for irrevocable loss of brain tissue and brain function during TBI. They are now exploring Caspase-8 as a target for the design of new TBI treatments.
Drs. Stuart Lipton and Joachim Speiss are working on a prototype drug that reduces TBI damage in animal models.