© MOMENT/GETTY IMAGESIn 1993, National Institutes of Health (NIH) researchers gave Eli Lilly’s promising experimental hepatitis B drug fialuridine to 15 patients as part of a small Phase 2 trial. It did not go well. Five of the patients died; two more required emergency liver transplants.
Fialuridine had undergone toxicity testing in mice, rats, dogs, and even nonhuman primates with no apparent ill effects, so the disastrous trial outcome was shocking. Years later, research revealed that drug uptake occurred via a transporter expressed in human mitochondria but not in the mitochondria of mice. Researchers now hypothesize that fialuridine builds up to toxic levels within mitochondria of the human liver, leading to catastrophic damage.
Fialuridine’s dramatic failure is an extreme case, but it exemplifies a fundamental challenge that the pharmaceutical industry faces: model organisms are imperfect predictors of drug safety and efficacy.
One way to improve the translation of drugs from animal models to the clinic is to make lab mice more human—specifically, to genetically engineer mice to express human proteins or ...
