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Mice to men: Immunological research vaults into the 21st century

Much of what we've learned about immunology has been learned from mice. But Mark Davis, PhD, thinks we're bumping up against an evolutionary limit. Having diverged from a common ancestor 60 million years ago, mice and people are - how to say this gently? - different. They've got four legs; we've got two. Their hearts beat 500 times a minute; ours 60. And their immune systems are different, too.

A few years ago, Davis, who is the director of Stanford's Institute for Immunity, Transplantation and Infection, and veteran Stanford immunologist Garry Fathman, MD, took some concrete steps to move beyond mice and start pointing their instruments straight at people's immune systems to help track human health and fight human disease. The results - namely, a thriving complex of state-of-the-art instrumentation and bioinformatics called the Human Immune Monitoring Center - are chronicled in this Inside Stanford Medicine feature.

Scientists can't just pivot effortlessly from mice to humans, running the same "look-at-one-thing-at-a-time" experiments on the latter as they did on the former, says Davis. (The patients wouldn't like it, and the bioethicists won't let you anyway.) But there's another way to get at the incredibly complex maze of cells, secretions, and signals that is the human immune system, and it goes by the name of systems biology.

"Suppose you've got a very complicated system, with a lot of moving parts," Davis says. "You don't know how those parts talk to one another. You don't even know where to start. So instead, you keep your eye on the whole thing, and you watch what happens to the parts when you hit it with a hammer. Some of the parts move together. Some move one after another. Then, you hit it with something else - a bucket of ice water, maybe - and see what moves this time, and when, and how much."

In this approach, the coin of the realm is human blood, samples of which are parsed out to high-tech, high-speed instruments that measure thousands of factors without any bias as to which of those factors are going to prove important. Instead, computers do the heavy lifting that identifies subtle signals separating a normally functioning immune system from a malfunctioning one - perhaps even before anything has gone visibly wrong. The effort may lead to a better understanding of what constitutes a "normal" human immune system - and, one hopes, to new ways of preventing and curing human disease. What works in a mouse often doesn't work in us people.

"We've cured cancer and autoimmune disease in mice many times over," muses Davis, who says a colleague of his often starts his talks with the salutation: "For the mice in the audience, I have wonderful news!"

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