“Failure to Communicate” due to Forgetting “Marriage Vow”?

I have followed the debate between Drs. Lenfant and Macklem, two highly respected leaders in the field of lung biology, which came to a head recently in this journal (1, 2). As a member of the lung research community for more than 30 years, I share their concerns. I am afraid though that they still have not focused on the key element in the “failure to communicate” (3): biology has been sacrificed on the altar of reductionist molecular biology (an oxymoron). The genes that have been identified by the Human Genome Project (HGP) are merely the end result of evolution that forms the basis for the mechanisms of physiology. These genes must be seen within their biologic context to discern cause and effect (4). The processes of development, homeostasis, and repair, which are studied in contemporary biology, are “snapshots” of the ongoing evolutionary process, particularly after the Cambrian Burst, given that only 1% of today’s species survived that event. Like the physicists, we too need to consider initial conditions to know where we are going as a species. Without working models of lung biology that vertically integrate genes in pathways that integrate cell–cell communication leading to development, homeostasis, and repair (5), we may never effectively extricate ourselves from the morass of information exploding in a processless void. Metaphorically, it is like grinding up a painting, analyzing its chemical composition, and expecting to understand what the artist intended to communicate. I thought we had learned this lesson from the endocrinologists, who finally realized that ligand– receptor relationships must be seen within their biologic context. After all, that is how steroid receptors were first discovered (6), by observing the fate of the estrogen receptor within the context of the estrus cycle of the rat uterus. I believe that we are currently at the same stage of scientific interrogation that we were 40 years ago when biochemistry was the tool being used to leverage pathophysiology. In the postHGP era, we need to apply molecular biology to biology, not the other way around. The lack of attention to biological principles has caused the “failure to communicate” between the basic scientists and the translators. Using Dr. Macklem’s divorce metaphor (7), marriages sometimes fail because the partners grow apart; perhaps we can counsel this marriage by putting biology back into the relationship between science and medicine.

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