In medicine and biomedical research physicians and scientists are challenged every day to understand biological processes as they occur in the context of the living organism. For example, we would like to learn more about what determines the spread of tumors in the body, how bacteria invade through the barriers of skin, lung, and intestine, and how the immune system strives to eliminate them. This paper describes the highly sensitive and versatile method of in vivo bioluminescence imaging (BLI) with which all of these and many other biological processes can be observed noninvasively over time in living animals that serve as models of various human diseases such as cancer. We also reviewed the advances that have improved the utility of BLI, one of several tools in the newly emerging field of Molecular Imaging. The development of BLI came through the combination of "glow-in-the-dark" reporters, such as the light-emitting enzyme from the firefly, with high-sensitivity video cameras. As few as one hundred tumor cells or bacteria labeled with a "glow-in-the-dark" reporter can be seen with BLI as they shine from within the animal, which is orders of magnitude more sensitive than other, and often more costly, imaging technologies. Thus, investigators can, for example, rapidly assess the effects of experimental drugs on cancer cells or infectious agents in the animal and advance our understanding of biology where it matters the most—in the complex environment of a living animal. The broad applicability of this method to a variety of questions in biology and medicine, and the relative ease of use, in comparison with other imaging tools, has led investigators all over the world to use BLI in numerous research settings, from basic developmental biology, cancer, and immune biology to pharmacological applications and surgical interventions. Our paper, published in Annual Reviews of Biomedical Engineering is a fairly comprehensive review that supports the experimental studies that use this technology.

  Does it describe a new discovery or a new methodology that's useful to others?

This method was developed in the mid-90s at Stanford University and is extremely useful for researchers from many biomedical fields situated in academia, biotechnology, and pharmaceutical companies. The basic technology has been licensed from Stanford University by Xenogen Corp. (Alameda, CA) and this company has made significant refinements and facilitated incorporation of this technology into many research programs.

This paper describes a method of using genes from "glow-in-the-dark" organisms—like the firefly, or lightning bug—to tag biological entities, such as cancer cells, infectious bacteria or developmentally regulated genes. The tagged cells or activity of the tagged genes can then be monitored, typically in a living mouse or other rodent, without opening the animal up just by detecting the light that travels from within the animal through its overlying tissues such as bone, muscle, and skin. In this way we have developed biological indicator lights that tell us, often over the course of many days to months, how cancer cells spread to other locations in the body, how bacteria invade and how immune cells mature and fight back, and we thus have an easier time studying what influences each of these biological events.

Out of the frustration of not being able to study biology in real time, i.e. as it is taking place in the living animal, we began to develop and combine tools from molecular biology and physics that together allow us to very much "see" biological changes as they occur in living animals.

Christopher H. Contag
Department of Pediatrics
Stanford University School of Medicine
Stanford, CA, USA