Whole animal physiology redux

EVEN THOUGH I RETIRED COMPLETELY in 1998 and vowed never to attend another meeting, I had to renege because it is such a great honor to be invited to give this lecture honoring my mentor, Julius Comroe. I thank the selection committee for considering me. Of the nine scientists chosen since this lecture was established, I may be the first unreconstructed, whole animal physiologist. Before I left San Francisco for New Orleans, I received one of the abstract volumes for Experimental Biology 2002. On the airplane and in my hotel room, I studied the pulmonary abstracts, of which I identified about 115. I made a list of the species used in the investigations, including 30 rats; 24 humans; 14 mice; 11 dogs; 4 rabbits; 3 each cats, rabbits, and goats; but only 1 sheep. Ten years ago, I would have expected 20 abstracts using sheep. Not only has the distribution of species changed, but intact animals were not used in many of the studies. For example, you might think that 24 experiments involving humans is encouraging, but in most reports, the humans were used to obtain populations of cells or proteins by lung lavage or from blood samples. Those do not qualify as integrative biological studies, in my opinion. A serious malaise has overtaken physiology. Physiology has become so bedazzled by molecular biology that physiologists are not producing new physiological insights. I have nothing against petri dish or test tube physiology. I have done many such studies. In its place, it is useful. What I decry is not the rise of mouse physiology but the decrease of whole animal physiology. So, I have been considering what I should say today that might make a useful contribution to physiology, the queen and mother of biological sciences. I’ve decided that the overall theme of my talk will be a question: Why has the potential for applications of molecular biology in clinical medicine not been realized? In 1990, I took a sabbatical to learn more about macrophage biology and molecular research. I learned many useful techniques. I even did some experiments to demonstrate that macrophages selectively phagocytize apoptotic leukocytes. But the most important thing I learned was that it is not my kind of research. I am too impatient to wait for a macrophage to ingest an old leukocyte, and I find reading blots boring. I need to record and measure things as I go along, antiquated physiological measures such as lung lymph flow, body temperature, pulmonary arterial blood pressure, and cardiac output. In 1993, the year I officially retired, I received a small grant from the American Heart Association (AHA). The award was due almost entirely to my longtime friend, Prof. Aubrey Taylor of the University of South Alabama, who lobbied on my behalf. The next year, the AHA changed its rules, so that old, unreconstructed physiologists would not be eligible for grants. I spent the next four years in the laboratory working with Dr. Kim Longworth at the University of California Davis. This brings me to what I believe is the problem behind my theme question (Fig. 1). There is a disconnection between molecular biology and clinical medicine because whole animal physiology has been downplayed, sidetracked. Despite fundamental discoveries, there is an enormous gap separating molecular biology from the treatment of disease. Few of the touted applications work. Some have unexpected, even dangerous consequences. That’s some disconnection! I believe the gap can be bridged if physiologists lobby and promote