Would Darwin Get a Grant Today?

Natural History, June, 2001 by T.V. Rajan

For the first half of the twentieth century, biological research was dominated by scientists who studied whole organisms in their natural settings. In recent decades, this approach to the study of life has increasingly been perceived as a poor cousin to molecular biology and has even, in some scientific circles, been contemptuously dismissed as stamp collecting. The change began as several forces conspired to bring about a reductionist approach. One powerful influence was the 1944 publication of a book entitled What Is Life? by Austrian physicist Erwin Schrodinger, whose work was vital to the development of quantum mechanics. In this book, Schrodinger maintained that physics could help explain why genetic traits are so stable--why, for example, a particular malformation of the lips (known as the Hapsburg lip) turned up over several centuries in members of the German royal family.

Physicists who felt that quantum mechanics had exhausted the possibilities offered by inanimate objects were inspired by Schrodinger's words to turn their attention to biology. These scientists brought with them the bias that studying individual molecules was the only plausible approach to understanding systems as complex as living organisms. This approach produced a massive explosion in our understanding of the molecular basis of life, teaching us that organisms derive their enormous complexity from a vast number of relatively simple interactive systems. Unfortunately, I feel, the molecular biology revolution has put the baby at risk of being thrown out with the bathwater.

I am often involved in reviewing grant proposals in my own field--biomedical research--and over the years have witnessed a disturbing trend. Nearly all the worthy molecular studies receive the funding they need, while many promising clinical projects--following the progression of a disease in real human patients, for instance--are turned down. This is regrettable, because both approaches are critical to understanding the many complex factors involved in any disease: the genes that may predispose someone to a particular illness, the environmental or other triggers that may bring on the illness, and the numerous factors (some, but not all of them, genetic) that determine how the illness progresses.

Some scientists believe that genetic information will soon render clinical or descriptive research moot. I am skeptical. The precise amino-acid substitution in the hemoglobin of patients with sickle-cell anemia has been known for approximately forty years; so far, however, this knowledge has done little to help manage the disease. The inevitable time lag between a genetic discovery and any alleviation of human suffering that might result from the discovery should be grounds enough to dictate steady financial support of clinical as well as molecular studies.

Furthermore, nature is notoriously frugal with her resources. Most genes play multiple, often little-understood roles in an organism. Altering a gene in order to treat one condition may leave the patient vulnerable to other problems. For example, the early onset of puberty in girls is associated with health risks, including an increase in the chance of developing breast cancer, so why not try to inhibit premature menarche? The enzyme responsible for breaking down the male hormone testosterone (which females also have, though in lesser amounts) may cause premature menarche. Wouldn't it make sense to tinker with the enzyme in order to increase a girl's testosterone level? No, because tinkering with it would adversely affect other areas of her physiology, such as her susceptibility to cardiovascular disease.

My concerns are not limited to medicine. I fear we may be discouraging many young people--the possible intellectual descendants of Darwin--who might otherwise choose to study organisms in the wild. In my view, this is tragic. As much as molecular biology and genomics can teach us, to deeply understand living organisms requires that we also study how their physiology is structured, how they evolved, and how they function in their current ecological settings.

Fortunately, as readers of Natural History know, field biology is far from dead, and many field biologists are now incorporating molecular biology into their research programs. As we begin to appreciate the limits of reductionism, I am optimistic that descriptive biology will come back into fashion and once again be recognized as an essential part of our efforts to understand life.

T. V. Rajan is chairman of the pathology department at the University of Connecticut Health Center in Farmington.