Director’s Corner

July 17, 2019: Reflecting on Our Own “Space” Explorations on the 50th Anniversary of the Apollo 11 Moon Landing

Christopher Austin

When I was a boy, I was captivated by space exploration. On July 20, 1969, along with millions of others around the world, I watched the Apollo 11 moon landing live on our fuzzy black-and-white television and heard Neil Armstrong’s iconic pronouncement of “One small step for man, one giant leap for mankind.” More than any other single event, this experience hooked me onto a life-long passion for exploration. I wanted to “boldly go where no one has gone before,” as proclaimed in the Star Trek introduction. Science beckoned with that opportunity and still does. Although I did not become an astronaut, I became an explorer of a different kind of space: biological and chemical space. On this 50th anniversary of the Apollo landing, I want to share why I believe exploration of these spaces has just as profound implications for science, medicine and society.

For our purposes, “biological space” refers to the sum total of all gene products—principally proteins, but also other molecule types—that exist in humans. The number of human genes is about 20,000, and the number of molecules our cells make from those genes is close to one million. Each of these molecules could hypothetically cause a disease if it malfunctions, and each could be the target of a drug. “Chemical space” refers to the sum total of all possible compounds with the structure and properties of drugs. That number is almost unfathomably large: 1060, or 10 with sixty zeros after it—about the number of atoms in the known universe.

The name of the game in translation is to match entries in biological space with those in chemical space. That is, for a given molecular target involved in a disease, what drug structures bind to it, activate it or inactivate it? If we knew these answers for all biological targets, drug development would be dramatically more efficient. Unfortunately, fewer than 10% of biological targets have been matched with chemical modulators (i.e., potential drugs), and chemicals that match to the other 90% will likely require us to develop compounds never made before. But which compounds should we make, if chemical space is so vast as to be functionally infinite? In the history of chemistry, only about 100 million compounds (108) have been made, leaving 1052 to go!

This is where exploring chemical space comes in. Earlier this year, NCATS launched its program to explore biologically active chemical space, appropriately named ASPIRE. ASPIRE aims to map unexplored biologically active chemical space by integrating automated synthetic chemistry, high-throughput biology and artificial intelligence technologies.

Like the Apollo mission, exploring chemical space will require the development of new technologies, new teams with previously unheard-of range of expertise and dynamic project management that will allow the teams to take advantage of unexpected opportunities and respond to inevitable setbacks. Much like space exploration, ASPIRE is an ambitious vision that we hope will spawn new technologies, excite a generation of aspiring scientists and produce solutions to previously intractable challenges in science and medicine.

Christopher P. Austin, M.D.
Director
National Center for Advancing Translational Sciences