Let's focus on humans
In 2008, Stanford immunologist Mark Davis, frustrated that virtually none of the advances in basic immunology had been incorporated into standard medical practice, wrote a polemic against the reigning mouse model.
Efficient, small and amenable to the most advanced tools of genetic engineering, the mouse is at the center of modern biomedical research. And while the mouse model has been spectacularly successful in elucidating basic biological mechanisms, its clinical usefulness has been much more limited. In the mouse, we’ve cured cancer, treated spinal cord injury and vaccinated against HIV — many times over.
It seemed obvious to Mark that the prevailing research paradigm in his field was broken. Yet his piece in Immunity was met with disregard and disbelief. Mark, like so many of his colleagues, had built a very successful career using experimental mice. So much had collectively been invested in the mouse model that few were ready to admit it was time to explore new approaches.
Mark knew that in order for colleagues to take seriously his criticism, he needed to suggest an alternative. In “A Prescription for Human Immunology,” he proposed the human “model.” With the availability of millions of blood specimens and advanced molecular technologies, he suggested immunologists deploy a systems approach to understanding the interactions in our staggeringly complex immune system. Using advanced instrumentation and techniques that in many cases were pioneered here, the Human Immune Monitoring Center at Stanford is the only facility of its kind that allows researchers to perturb the immune system and then sit back and watch the hundreds of interactions among the moving parts.
In suggesting a focus on humans, Mark was proposing an entirely new research paradigm. But it was little more than a thought experiment at the time. Since then, important discoveries have validated his approach. One study found that our bodies build up immunity by exposure to harmless, as well as harmful, pathogens — perhaps an evolutionary clue as to why kids eat dirt. Another study linked high testosterone levels in men to a weakened immune response to the flu vaccine. It has long been known that men do not respond as strongly to vaccination as do women. The new study may explain why this is the case.
Mark’s paradigm-shifting work is the kind of scientific creativity that characterizes Stanford Medicine. In laboratories around the world, scientific progress happens when researchers pursue a novel idea. But since scientific disciplines are bound by paradigms of agreed-upon methods and models, innovation often requires researchers to pursue a revolutionary idea that proposes an entirely new paradigm altogether. Here at Stanford Medicine we are not satisfied with incremental progress, with leaving well enough alone. We’re willing to risk failure in the hope of achieving something great.
By decreasing our reliance on surrogate models of disease, we can speed the translation of advances in biomedical knowledge into tangible benefits for human health. In this way, Mark Davis’ provocation was more than a call to his fellow immunologists; it was a call to scientists everywhere.
Carl and Elizabeth Naumann Dean of the School of Medicine
Professor of Otolaryngology-Head & Neck Surgery