Breath Taking. Michael J. Stephen

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СКАЧАТЬ babies died from mysterious lung illness, Dr. Avery was at their autopsies, going over their pathology, holding on to the slides for the day when she could make more of a connection between them. One thing that caught her attention during these autopsies was how dense with tissue these little baby lungs were, completely airless, resembling the liver more than the lung. They had failed to inflate.

      Dr. Avery visited the library at the Massachusetts Institute of Technology (MIT) on weekends, seeking literature from fields outside of medicine, hunting for new ideas from the minds of chemists and mathematicians. On one of these visits she discovered a book by C. V. Boys entitled Soap Bubbles: Their Colours and Forces Which Mould Them.

      First published in 1912 for English schoolboys, this slim volume was a primer on the physical properties that govern soap bubbles, filled with simple experiments that document the physical properties of liquids and their interaction with air, explaining how soap bubbles are able to stay intact, miraculously floating through the air. Dr. Avery saw a connection between soap bubbles and the alveoli in our lungs. Circular in shape, and needing to stay open to continue gas exchange, alveoli are governed by the same physical laws as those governing soap bubbles.

      The key to soap bubbles staying spherical and not collapsing in on themselves lies in their surface tension. Any spherical structure, like a soap bubble or an alveolus in the lung, is bound by a simple law of physics. Formulated by French scientist Pierre-Simon Laplace and English mathematician Thomas Young in 1805, the law states that the pressure exerted on a circular structure is directly proportional to the surface tension in the sphere, and inversely proportional to the radius of the sphere. Extrapolated out, this means that larger bubbles are more stable and have less pressure on them than smaller bubbles, and they are more likely to stay intact. Similarly, a sphere with lower surface tension is more stable and is under less pressure than one with higher surface tension.

      The radius of a sphere is simply the distance from the center of the sphere to any edge. Surface tension, however, is more complicated. At the interface between a liquid and a gas, the molecules in the liquid are more tightly bound together than in other areas of the liquid. For example, in a glass of water the water molecules at the surface are much more crowded together than the molecules in the middle of the glass, because there are no water molecules above them to exert a dispersing force. These tightly bunched water molecules at the surface cause tension, which produces the slight dip one can see at the top of a glass of water.

      Different liquids have different tendencies to bunch together at the surface. Water has a relatively high surface tension, so molecules are bunched relatively tightly together at its surface. Consequently, water does not make a good bubble, and exists more easily in drops, like rain drops and drops of water in a sink. But if soap is added to water, the surface tension is dramatically lowered. The ends of soap molecules have different properties: one end attracts water (hydrophilic), and the other one repels water (hydrophobic). When placed in water, the hydrophobic ends of soap molecules push their way to the top, which causes the water molecules to separate from one another, lowering the tension and energy between them. This allows a spherical structure like a soap bubble to stay intact, until it dries out and bursts.

At the same time Dr. Avery was learning about bubbles and surface tension, a number of committed scientists, employed by the federal government at the height of the Cold War, were investigating properties of the lung in reaction to chemical warfare. The lungs are a typical entry point for poisonous gases, and understanding the effects of toxins on the lung and how to combat them was a priority. One of these researchers, Dr. John Clements, at the Army base in Bethesda, Maryland, undertook a series of experiments in the mid 1950s to quantitatively measure surface tension in the lung, which demonstrated that lung tissue had very low surface tension compared to other tissues. He then did something simple, which nobody had ever done: he measured pressure across extracted lung tissue with expansion and contraction. As mentioned, the pressure on a sphere like a soap bubble or a lung alveolus is proportional to its surface tension divided by its radius, and lower pressures will mean the bubble will have a greater chance of not collapsing in on itself. Remarkably, the pressure decreased significantly with lung contraction (as the alveoli in the lung were getting small with contraction, pressure should have increased as the radius decreased), and increased significantly with expansion (as the alveoli got bigger, pressure should have decreased as the radius increased). To explain this, Dr. Clements correctly postulated that something must be overcoming the effect of size on pressure, and the only variable left in Laplace’s equation was surface tension.42

      Taking his hypothesis further, Dr. Clements imagined that something within the lung must be lowering surface tension so dramatically as to overcome the effect of size on pressure. He correctly postulated it was a soap-like foam, which exerted a dispersal effect as its molecules became more concentrated and the area became smaller, and lost this effect when the lung expanded and pulled the soap like foam molecules apart. The effect of this soap-like foam lowering surface tension would be more important than lung size in calculating pressure if it was a powerful substance (which it was, and is). John Clements later named this substance surfactant, from its effects on the surface tension.

      Figure 7: The lungs in cross section, with a conducting airway surrounded by many alveoli.

      The definitive discovery and demonstration of the existence of surfactant was a major breakthrough in the understanding of lung physiology, finally explaining the mechanism by which the lung seamlessly expands and contracts, thousands of times a day, without breaking apart with inspiration or collapsing with exhalation. While the heart has dense striated muscle, and the brain its conglomerated networks of communicating neurons, the lung is a thin, graceful structure of interconnecting fibrous tissue that is beautifully held together with a foamy substance that lubricates its functions in a quiet and effortless manner. It is an organ of elegance, not brute strength.

John Clements’s paper did not get accepted into the high-powered journal Nature, but appeared instead in a low-level publication, where it was not widely recognized as the landmark study it would become.43 It did, however, reach Dr. Avery, and in 1956 she drove to Bethesda to meet Dr. Clements in person. He knew nothing about neonatal respiratory distress, and she knew nothing about how to properly measure surface tension. He taught her everything he knew about lung physiology, as well as how to build an instrument so she could take her own pressure and surface tension measurements. Dr. Avery quickly came to believe that the afflicted newborns weren’t diseased because of the presence of something, that something being hyaline membranes, but because of the absence of something.44 That something, she believed, was surfactant.

      She went back to her lab and built her own balance to measure surface tension, and then she discerned that the lungs of babies who had died from respiratory distress syndrome had very high surface tension. By comparison, the lungs of normal infants had a much lower surface tension. This was the breakthrough she had been looking for since her time as a child visiting the hospital with Dr. Bacon, and the breakthrough humanity had been waiting for since the first premature baby had been born and died a perplexing death.

Dr. Avery published her findings in 1959 in the American Journal of Diseases of Children. Entitled “Surface Properties in Relation to Atelectasis and Hyaline Membrane Disease,” the paper broke the field of neonatal respiratory distress syndrome wide open.45 The key to the disease had been pinpointed. The immature lungs were not making surfactant, the surface tension in the alveoli was way too high, and the alveoli were crashing closed. Hyaline membranes were formed as a byproduct of the inflammation and destruction. Some babies lived long enough for surfactant production to kick in and open up their alveoli, but many did not.

      Funding poured in from the National Institutes of Health, and over the ensuing decades, researchers at several different institutions made significant progress toward a cure. Doctors used ventilators to stent the lungs and alveoli open, and steroids were shown to СКАЧАТЬ