For the last several years, Stanford immunologist Mark Davis, PhD, has been pushing the immunology field to steer research away from a reliance on mice and toward humans. He recently talked about his reasons for this in a Q&A piece in Annual Reviews‘ science-friendly online magazine Knowable.
Davis is an easy subject for a science journalist. Huge volumes of medical literature have flowed from his discoveries. We now understand much more about how T-cells, the immune system’s roving sentinel and special-forces troops, fight disease — or, if they’re either too lazy or active when they shouldn’t be, cause it.
Davis first tore the cover off the ball as a young postdoc at the NIH and then as a Stanford faculty member in the early 1980s. Using what would now be considered laughably primitive methodologies (because that’s all there was back then), he scooped Nobelist competitors and succeeded in unraveling the DNA sequence of a pair of key genes encoding the two constituent pieces of the T-cell receptor, which is the molecular equivalent of a claw-like catcher’s glove that latches onto tiny chunks of proteinaceous matter, called antigens, on cell surfaces. That sets in motion an analysis by the T cell as to whether the cell in question deserves to be left alone in peace or — if the chunks indicate the cell is infected or cancerous — attacked and destroyed. The judgment a T cell passes on those cell-surface antigens is an absolutely essential determinant in immune response.
Although numerous recent findings in the Davis laboratory have derived from his pioneering focus on us people — often via multifarious measurement of cells, chemicals, and signaling activities in human blood samples, studies of twins, and so forth — much of what we know about the immune system comes from experiments conducted on mice, as Davis readily acknowledges. Quite frankly, you can do experiments with mice that would be impossible or forbidden on human subjects.
But lab mice are not little human beings. The two species are separated by both physiology and lifestyles. 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 differ physiologically, too.
Plus, lab mice lead very different lives from the ones we do, notes Davis in the Knowable Q&A:
We don’t want the mice we work with to get diseases. We put them in the basement covered with HEPA filters. I’ve never seen an immunologist so angry as when someone tells them there’s a disease in the mouse house. It will ruin your experiments. But here we humans are, coughing and sneezing and getting all sorts of afflictions from birth. The mouse is a very imperfect representation of the human immune system, and we’re never going to know how similar or different it is unless we have human data.
“We’ve cured cancer and autoimmune disease in mice many times over,” Davis likes to say. And he says a colleague of his often starts his talks with the salutation: “For the mice in the audience, I have wonderful news!”
Photo by Timothy Archibald