in humans. Emerging safety science holds promise for enriching this traditional approach.

Much of emerging safety science is predicated on going beyond observations in whole animals or in organ systems to look at what is happening within a cell—to understand which pathways are perturbed, for example. Adding this information to the traditional approach could even allow researchers in the future to sidestep the traditional animal experiments altogether because of the ability to predict directly what will happen in humans. One advantage of studying actual human cells and human pathways is that it obviates the need to extrapolate from other species. Furthermore, as various presentations at the workshop demonstrated, this approach offers an explanatory power that is lacking with the traditional animal experimentation. By providing information such as gene transcription data, emerging safety science techniques can offer insight into what pathways, targets, or receptors have been perturbed. This information can then be applied to understand and predict the kinds of events that can be expected in humans who take a drug.

Thomas Caskey, of the University of Texas Health Science Center at Houston, identified two areas he believes will be important for prediction in the future but were not discussed as thoroughly at the workshop as some others. The first is the use of protein assays. He argued that although proteomics technology is more challenging and not as well developed as transcriptomics or metabolomics, proteomics assays can be easy to conduct when one knows what to measure, and will eventually prove to be important. The second area is imaging. Alluding to Westwick’s description of an imaging technology used in a human cell–based screening technique (see Chapter 3), he suggested that such imaging technologies will likely prove to be very powerful because they can be extended from cells to whole animals, and thus be used to determine whether what is seen in individual cells is also seen in more complex systems.

The techniques described during the workshop, such as gene transcription and metabolomics, are already being used to discriminate among drug candidates. Throughout development, they are being used to help select targets, classes, or doses. There are also examples of their being used to prevent adverse events in humans and of markers being identified to help monitor for effects in humans, thus minimizing the chances of drug-induced injury. Finally, these techniques are being used to gain additional information about cellular pathways and signaling, thereby increasing understanding of why certain events occur and offering insights into potential new targets.



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