© 2004 American Thoracic Society
"Failure to Communicate" due to Forgetting "Marriage Vow"?To the Editor: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 post-HGP 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.
Harbor-UCLA Medical Center Los Angeles, California FOOTNOTES Conflict of Interest Statement: J.S.T. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. Dr. Claude Lenfant was given the opportunity to respond to this letter but declined to do so. REFERENCES
From the Author: I do not disagree with Dr. Torday's eloquent argument in response to the debate between Dr. Lenfant and myself (1, 2). There is no doubt that the genes we possess are the end result of many millions of years of Darwinian evolution, and their function can only be fully understood in that context. What is missing from this view is that genes are only part of evolution's story. The origins of order are of equal importance (3, 4). This complex, self-organizing process requires dissipation of energy in a far-from-equilibrium state in which initial conditions are of utmost importance (5). Self-organization is as crucial to medicine as genetic biology, but it has hardly been a priority of granting agencies. In addition, it has been convincingly argued by Polanyi (6) that revealing the secrets of life requires understanding of the boundary conditions (another term borrowed from physics) that control and harness the physical and chemical processes that go on in our bodies. These boundary conditions are not reducible to the laws of physics and chemistry, just as the meaning of a painting is not reducible to the properties of the paint (6). Dr. Torday's metaphor is precisely what Polanyi discusses. Molecular biology studies the paint, whereas what should be studied is the strategy of the artist. In my view, the "key element in the failure to communicate" is that strategies inherent in complex systems and boundary conditions are missing from molecular biology. Advancement of medicine requires detailed knowledge of these strategies, because in health they govern morphogenesis, homeostasis, and regeneration; in disease, they break down. Molecular interactions and self-organizing systems obey the physical and chemical laws of nature, but the boundary conditions do not. This poses problems because if Polanyi is correct, they cannot be addressed by the laws of physics and chemistry. Polanyi (6) states: Recognition of the impossibility of understanding living things in terms of physics and chemistry, far from setting limits to our understanding of life, will guide it in the right direction. And even if the demonstration of this impossibility should prove of no great advantage in the pursuit of discovery, such a demonstration would help to draw a truer image of life and man than that given us by the present basic concepts of biology.
McGill University Health Centre Montreal, Quebec, Canada FOOTNOTES Conflict of Interest Statement: P.T.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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