Designing Mice for Human Healing

Terra-mice

You can order them in yellow, two-tone (black-and-tan), “misty,” beige, “chinchilla” and lots of other colors and tints. They’re not handbags or home appliances, but like those other products they’re designed by humans and available for purchase on the Internet.

These multicolored commodities are research mice, and they can be credited for countless biomedical breakthroughs in cancer and other diseases. In the “benchtop-to-bedside” slog toward drug discovery, animal studies are the step between the petri dish and the human trial, says OSU’s attending veterinarian Dr. Helen Diggs.

“With mice, we’re able to look at cancer — the growth of tumors, the spread of malignancies — in a way we could never do in a human patient,” says Diggs, who oversees the health and wellbeing of OSU’s 400,000 research animals. “You can see how fast it grows, where it spreads and how it responds when you treat it with a drug you’ve developed.”

Helen Diggs
Helen Diggs

The varied hues in the rodents’ fur coats manifest outwardly the genetic makeup of their DNA — makeup that has been manipulated in the lab. Take the yellow mouse as a hypothetical example. Let’s say it’s missing a gene that protects against ovarian cancer. That missing gene was lost on purpose, “knocked out” of the animal’s DNA sequence by scientists at a federally regulated research animal facility. The beige mouse, on the other hand, might possess an extra gene that promotes prostate cancer — a gene that was intentionally inserted or “knocked in” to the mouse’s DNA.

In essence, Diggs explains, “You’re removing or adding pieces of material to the mouse’s genetic sequence in order to trigger or prevent an ailment.”

These genetically engineered mice (GEMs for short) allow scientists to study cancer, obesity, HIV, Alzheimer’s and a host of other human diseases without risk to human patients. Because the mouse genome is similar to the human genome, treatments can be tested in mice and then translated to human afflictions. Only after a drug’s safety and efficacy have been amply demonstrated in mice will the U.S. Food and Drug Administration consider trials in human subjects.

The Jackson Laboratory in Maine, which Diggs calls the “granddaddy” of all breeding facilities, is a major source of “knockout” and “knock-in” mice for Oregon State University, where about 25 researchers are currently conducting biomedical research with mouse models. Among them are Siva Kolluri in the Center for Genome Research and Biocomputing, who is studying new compounds for treating breast cancer; Adam Alani in the College of Pharmacy, who studies novel drug formulations for ovarian cancer; and Oleh Taratula, also in the College of Pharmacy, who is investigating the use of near-infrared light in treating ovarian cancer and melanoma.

Next door to Diggs’ office, lab animal technicians carefully prepare sanitized, custom-made cages with sterile water, special diets and bedding that encourages nesting behaviors. The cages will house shipments of mice from specially ventilated shipping containers. After their flight across the continent, the mice are closely monitored by the technicians and given extra TLC.

Costing as much as $300 each, the GEM animals are VIPs in the world of research rodents. But the treatment they receive under Diggs’ vigilance is no more rigorous than what’s given to a plain-brown $25 lab mouse.  When it comes to the stringent rules and regs that govern research animal care, she says, all creatures are created equal.