[An exploration of Linus Pauling’s popular rhetoric on the potential for science following World War II. This is part 2 of 5.]

“Modern structural chemistry.” [Acceptance speech for the Willard Gibbs Medal, awarded June 14, 1946 by the Chicago Section of the American Chemical Society] Chemical and Engineering News, July 1946.

In 1946, Linus Pauling was awarded the prestigious Willard Gibbs Medal by the Chicago section of the American Chemical Society for his work in structural chemistry. In thinking about his acceptance speech, Pauling ultimately chose to frame it as an overview of the history of modern structural chemistry.

Pauling began his talk with Lucretius who, in the first century BCE, began thinking about the properties of matter. Lucretius hypothesized that honey was made up of “smooth, round molecules which roll easily over the tongue, whereas wormwood and biting centaury consist of molecules which are hooked and sharp.” From there, Pauling rolled through the work of more contemporary greats including Lomonosov’s explanations of the properties of molecules in solid, liquid, and gaseous states; Dalton’s work on the weight relations of chemical reactions; and Avogadro and Cannizarro’s breakthroughs on chemical bonds.

Next up in the whirlwind tour were Frankland, Couper, and Kekulé’s theory of valence; Kekulé’s subsequent writings on the Structure of the benzene molecule; and van’t Hoff and le Bel’s explanation of the right and left-handedness of substances. Rounding out the history lesson were Werner’s work on the spatial arrangement of chemical bonds, and Lewis’ identification of the chemical bond as a pair of electrons shared between two atoms. One outcome of all of these advancements was that the discipline of structural chemistry had moved firmly in the direction of the quantitative as opposed to the qualitative judgments that had permeated Lucretius’ analyses of taste and mouth-feel.

Pauling then noted that some of the most exciting and important developments in the history of modern structural chemistry had occurred during his lifetime. It was, for example, only during the early years of his career that methods for accurately measuring interatomic distances had been developed. Subsequent breakthroughs in methodology had included molecular spectroscopy, x-ray and electron diffraction, and applied quantum mechanics, among others techniques. More recently, new knowledge had been produced about moments of inertia, oscillational frequencies, the elucidation of molecular structures for specific substances including sex hormones and vitamin D, and the discovery of the β-lactam configuration of penicillin. In surveying this work, Pauling was particularly quick to praise the usefulness of x-ray diffraction as a powerful tool.

As he looked ahead, Pauling expressed a belief that the most promising application of modern structural chemistry would be its ability to explain the physiological activity of chemical substances. Previous research in this area had produced few results of importance, but Pauling felt sure that the structures of numerous molecules would soon be elucidated, thus laying the groundwork for new insights into physiological activity and, eventually, medical research on diseases like cancer and cardiovascular illness.  

“Molecular Architecture and Medical Progress.” Radio talk broadcast on the New York Philharmonic-Symphony Radio Program and sponsored by the U. S. Rubber Company, October 13, 1946.

The ideas expressed by Pauling in Chicago were taken up again in this radio broadcast, which Pauling used to further explore the relationship between molecular structure and physiological activity. In attempting to make this relationship more understandable to his lay audience, he opened with the example of Penicillin G, a molecule commonly recognized as a powerful antibiotic.

Despite penicillin’s widespread application in medical contexts and its acknowledged significance to human life since its discovery in 1928, the molecule’s physiology, at the time of Pauling’s radio talk, was not well-understood. This circumstance was likewise true of other molecules that had become household names, including DDT, morphine, ether, and adrenaline. While scientists understood their uses and functions, the chemical activity that generates and determines those functions remained out of grasp.

Pauling believed that these connections, and the answers that they might provide, lay in what he called “their molecular architecture.” More specifically, were scientists able to determine the structures of specific molecules, they might then turn their attentions to the structures of the biochemical forms with which the molecule interacts. In the case of the household names molecules – penicillin, morphine and the like – these forms might include enzymes, nerve fibers, and tissues with which the molecules interact to produce a desired effect, such as killing bacteria or numbing pain.

Interatomic distance is one important aspect of molecular structure that Pauling took pains to emphasize to his audience. In order to convey a sense of the scale at which atomic distances are measured, Pauling created a hypothetical world where perspective was shifted in the direction of the commonplace. He began by stating that a single Angstrom – the unit used to measure interatomic distances – is equal to 1/254,000,000^th of an inch. In other words, when magnified by a factor of 254 million, one scaled-up Angstrom unit would be equivalent to one inch.

With proportions thus shifted, the average human being in Pauling’s hypothetical world would be about 250,000 miles tall, and a wineglass would be as big as the Earth. Importantly, were this gargantuan wineglass full of liquid chloroform, each individual chloroform molecule would be a mere seven inches across. A molecule of chloroform is made up of one carbon atom, three chlorine atoms, and one hydrogen atom, and on this scale, the carbon atom would be the size of a walnut, each chlorine atom the size of a small orange, and the distance between the walnut and each orange would be 1.76 inches. Scaled back down to its actual size (that is, a wineglass-sized wineglass), that distance would be 1.76 Angstrom units.

Pauling’s point in developing this hypothetical was that, in part because they are both small and complicated, the structures of organic compounds were poorly understood. “This then is the great problem of modern chemistry,” Pauling suggested, “the determination of the molecular architecture of the proteins and other complex constituents of the living organism.”

Indeed, Pauling believed that progress in medicine was particularly dependent upon an improved understanding of molecular structure and physiology. By extension, he saw the future role of the “medical research man” as being equivalent to a “molecular architect.” Armed with an understanding of the molecular structures underlying physiological reactions, this new style of architect would have the ability to create “atomic blueprints” for pharmacological compounds designed specifically to treat particular illnesses.