The mice that act like humans

If human trials confirm that a daily pill can prevent HIV infections, J. Victor Garcia-Martinez's little mice could become huge.

The rodents, specially engineered to have human immune systems, are already considered important tools in HIV research.

Now they may prove to have highly predictive powers that will make them crucial for science that cannot easily or ethically be conducted outside a laboratory.

Garcia, who moved his lab and research team last year to UNC-Chapel Hill from the University of Texas Southwestern Medical Center, said his mice could speed the pace of discovery and cut costs, giving researchers a better idea of which drugs have the best prospects in human trials.

"Human trials take years before they're completed," Garcia said, noting that only some bear successful results.

In the worst instances, people are put in harm's way. A recent trial for a topical HIV barrier gel that looked promising in laboratory studies did not provide good protection for women. Similarly, a vaccine trial was halted three years ago when participants who took the drug candidate actually became more susceptible to HIV infection.

Such therapies are rolled out for human tests only after being tried in laboratory animals, including primates that are genetically similar to humans.

Dr. Myron Cohen, director of UNC-CH's Institute for Global Health and Infectious Diseases, said there are enough differences between primates and humans that even the best comparisons can be slightly off.

Instead, Garcia engineered mice to have human bone marrow, blood and thymus glands - all the equipment to function identically to a human's immune system when faced with a pathogen such as HIV.

The approach has generated enthusiasm among AIDS researchers.

"This would be a very promising model to accurately predict human responses," said Dr. Timothy Mastro, vice president of health and developmental sciences at Family Health International, which runs human HIV trials around the world.

Garcia said the humanized mice could be used in trials to test whether HIV develops resistance to anti-retroviral drugs used for prevention. Rather than wait to identify the problem if prevention pills go into wide use, scientists could get a head start in mice studies and develop strategies to either avoid or manage the problem.

"We can get ahead of the virus," Garcia said. "We can anticipate what is going to happen ... and that can lead to a faster response. This is going to open many new lines of investigation that really are going to advance the field."