Linus Pauling (1964) - The Structure of Molecules in Relation to Medical Problems

Linus Pauling (1964)

The Structure of Molecules in Relation to Medical Problems

Linus Pauling (1964)

The Structure of Molecules in Relation to Medical Problems

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Linus Pauling was an incredibly productive and versatile scientist. His work comprised fundamental problems from the fields of chemistry, physics and medicine. At the same time, his commitment ranged far beyond the borders of science. To this day, he is the only person who received two Nobel Prizes without co-recipients: the 1954 Nobel Prize in Chemistry for his work on the nature of the chemical bond and chemical structure as well as the 1962 Nobel Peace Prize for his fight against nuclear weapons. Pauling used his 1964 Lindau lecture to talk about some of his most recent research at the time, which he summarized under the umbrella of “chemistry in relation to medicine”. The first part of this talk concerns two diseases relating to haemoglobin, the protein responsible for oxygen transport in blood. In the second part, he tries to answer some seemingly trivial questions: how is it possible that xenon, a noble gas completely devoid of any physiologically relevant chemical reactivity, can act as a general anaesthetic? And is there a common mode of action of general anaesthetics? That these questions are indeed tricky ones can be seen from the fact that even today (2013), almost fifty years after Pauling’s talk, a satisfactorily comprehensive theory of general anaesthesia is still not available. Although general anaesthetics have been used for more than 150 years, we just do not know how they work entirely. In a couple of papers published from 1961 to 1964 [1-2], as well as in the present lecture, Pauling proposed that the only property common to all known anaesthetics is their effect on water crystallization and that the loss of consciousness achieved by anaesthesia is indeed due to the spontaneous formation of water microcrystals in the brain. While water itself naturally does not crystallize at the temperature of the human body, hydrates of certain other molecules possibly could, Pauling says. This is due to the fact that water crystals contain relatively large cavities, which are usually unoccupied (this is the reason for ice floating on top of liquid water). However, certain small molecules, like xenon, can occupy such cavities via the formation of hydrates and thus stabilize the crystal even at elevated temperatures. This stabilization is due to the so-called London dispersion force and does not require any chemical reaction to take place. In his “hydrate microcrystal theory of general anaesthesia” Pauling now proposes that such spontaneously formed microcrystals might interfere with the motion of ions or electrochemically charged protein side chains, which are essential to consciousness and short-term memory. He presents some convincing correlations between the polarizability of molecules (which determines the strength of the London dispersion forces) and its anaesthetic potential. However, in a 1964 paper [2], he also points out that his general theory is not so general after all: the effect of certain anaesthetics like the barbiturates and diethyl ether cannot be explained by it. Today, it is accepted that general anaesthetics do not act by one single mechanism but rather affect a number of specific protein targets [3], both in the brain and the spinal cord. A comprehensive explanation by a single mechanism thus appears unrealistic.The present lecture is the first of four lectures Pauling gave in Lindau. In 1977 and 1981 he should return to talk about his controversial suggestion that high vitamin C dosages could protect from cancer. His last Lindau lecture, held in 1983, dealt with the structure of transition metal compounds, whereas extended parts of it are dedicated to the issues of nuclear weapons and peace. David Siegel[1] L. Pauling, Science 134 (1961) 15.[2] L. Pauling, Anesthesia & Analgesia 43 (1964) 1.[3] N.P. Franks, Nature Reviews Neuroscience 9 (2008) 370.

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