In developing countermeasures for biological, chemical and radiological warfare you can’t, for obvious reasons, expose humans to nasty germs or high levels of radiation. You don’t want to expose animals to these pathogens either, if you can avoid it.
The same can be said for pharmaceutical research and testing. Until recently, during drug development animal subjects were the only way of obtaining data from inside a living organism (“in vivo”) to predict human pharmacological responses. It has been estimated that more than 100 million mice, cats, rabbits, dogs, etc. are used for different experiments each year. But besides the ethical issues involved, using animals is not necessarily a good predictor of human responses to new drugs because of fundamental differences in biology between species.
So let’s say you want to know—as the US Department of Homeland Security does-- how many anthrax spores are necessary to cause disease in the body. Or you want to know the effectiveness of a proposed drug while reducing some of the up-front costs—which can reach into the billions—during the research and development phase.
What do you do?
As an alternative, researchers around the country at Harvard University's Wyss Institute, the University of California at Berkeley, the Pacific Northwest National Laboratory and elsewhere are developing miniature organ-on-a-chip devices to test biological and radiological defense measures as well as new pharmaceuticals.
Lung-on-a-chip (above) can be used to study drug toxicity and potential new therapies. Source: Harvard's Wyss Institute
Wyss researchers are engineering microchips that model the microarchitecture and functions of living organs, such as the lung, heart, and intestine. These organs-on-a-chip devices could result in an accurate alternative to traditional animal testing. Each individual organ-on-a-chip is a cell culture device composed of a clear flexible polymer that contains microfluidic channels (to feed the cells with a nutrient-rich fluid to mimic blood) lined by living human cells and tissues. The goal is to create functional units that accurately model tissue- and organ-level functions, thus permitting real-time analysis of biochemical, genetic and metabolic activities within individual cells.
Since their initial publication in 2010 of a paper in the journal Science on a human, breathing lung-on-a-chip, and with grant support from the Defense Advanced Research Projects Agency (DARPA), the Food and Drug Administration (FDA) and the National Institutes of Health (NIH), the Wyss team has developed more than ten different Organs-on-a-Chip models including chips for liver, kidney and intestinal functions.
Bioengineers at the University of California, Berkeley also are combining human cells with computer chips, in this case to eliminate the need to test new heart medicines on animals and to reduce the associated unpredictability of these medicines when given to humans. The latter obstacle exists in part because of biological variables; the ion channels through which heart cells conduct electrical currents, for example, can vary in both number and type between humans and other animals. The pulsating cardiac muscle cells are housed in an inch-long silicone device that effectively models human heart tissue, and the researchers have demonstrated the viability of this system as a drug-screening tool by testing it with cardiovascular medications. Researchers reported on their study this week in the journal Scientific Reports. It is being funded by the Tissue Chip for Drug Screening Initiative, an interagency collaboration launched by the National Institutes of Health to develop three-dimensional human tissue chips that model the structure and function of human organs.
Similar research is being conducted at other facilities. At a meeting of the American Society for Microbiology (ASM) last week in Washington, DC, for example, researchers from the Pacific Northwest National Laboratory in Richland, Washington presented the results of their experiments to determine the ability of anthrax spores to infect a three-dimensional lung-on-a-chip which they developed using rabbit lung cells.
Can these devices make animal (and human) testing obsolete? Post your thoughts in the comments below.
