Engineering better medicines at the Stanford Institute for Chemical Biology

One of the most promising frontiers in medical discovery is the intersection of chemistry and human biology. Life scientists, physical scientists and engineers are working together to understand biological functions at an atomic level, visualize chemical interactions in living systems, and engineer molecules that can alter these functions and interactions in a predictable manner. To encourage this interdisciplinary effort the Institute for Chemical Biology has been established through the Office of the Dean of Research. The Institute involves the Schools of Engineering, Humanities & Sciences, and Medicine and also collaborates with the SLAC National Accelerator Laboratory. During the next decade, the Institute plans to recruit approximately 20 new faculty who will hold appointments in departments across the three schools and will collectively define this frontier. Chaitan Khosla, the Wells H. Rauser and Harold M. Petiprin Professor of Chemical Engineering and Chemistry, will direct the Institute. Here he speaks about its goals, methods and benefits.

Why must we rethink the process for engineering medicines?

The biggest problem in drug discovery today is that for many diseases we are entering very large-scale, late-stage human clinical trials with little more than a prayer of success. Given the costs of large clinical trials, those become half-a-billion dollar prayers. Molecular science and engineering can help by inventing tools that greatly enhance the odds of success when we get to those very expensive human experiments at the later stages of the drug pipeline.

How will the Institute address this challenge?

The human body is essentially composed of chemicals. We want to understand human biology in the language of chemistry. This knowledge will enhance our ability to engineer drugs that heal the body more effectively. It will also pave the way toward comprehensive disease management practices that harness advanced medical devices, diagnostics and monitoring tools. Simply put, the clearer we can visualize the molecules of life and their interactions with each other, the more successful we will be as drug discoverers.

How will you get those molecular pictures?

One of the ways will be our partnership with SLAC. Today, in North America, SLAC is arguably the best source of photons for life-science research and is therefore an invaluable resource for chemical biologists at Stanford. It has the ability to capture images of molecular structures. In particular, it has the world’s first X-ray free electron laser, which delivers extremely bright, ultrashort coherent X-rays with the potential to revolutionize the acquisition of snapshots and movies of biomolecules. We want to leverage that invaluable resource to understand the structural biology of disease targets or molecules. You’ve heard the metaphor that a picture is worth a thousand words. There are very few areas of science where that metaphor is more appropriate than in chemical biology. Sometimes you see the atomic structure of a molecule and it immediately suggests explanations for inexplicable biological phenomena that you may have been wrestling with for 10 years. Other times you see a molecule and you realize that you are looking at something you didn’t even know existed in nature.

How will the public derive a benefit from this work?

Two broad types of advances will emerge. The first will be a change in the way we view medical conditions that were once considered intractable. As we better understand these disorders at a chemical level, the scientific community will start to realize that these are solvable problems. The second kind of breakthrough will be new types of molecular technologies. These may be novel materials for tissue and organ regeneration or fundamentally new ways to image disease processes in the human body. Molecular engineering will help us approach some of human biology’s biggest challenges cheaper, faster, better.

This is an interdisciplinary effort. Why is that important?

Because these molecules of life are so complex that our work will require a wide variety of skills and approaches. That is the beauty of Stanford. We have amazingly gifted scientists, engineers and clinicians. The Institute for Chemical Biology will bring those researchers even closer intellectually and help them work together to design more insightful experiments at every step of the drug discovery process. Ultimately, this will increase the likelihood of success when we make those half-a-billion dollar prayers.