Pauling’s First Paper on the Nature of the Chemical Bond

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Linus and Ava Helen Pauling in Munich, with Walter Heitler (left) and Fritz London (right), 1927.

[An examination of Linus Pauling’s first paper on the nature of the chemical bond, published in April 1931. Part 2 of 2.]

In 1928 the German physicists Walter Heitler and Fritz London published a paper that appeared to have beaten Linus Pauling to the punch in its application of quantum mechanics to the theory of chemical bonding. As with Pauling, the duo was interested in Erwin Schrödinger’s wave function, and in their paper they applied it to the simplest bond: that formed by two hydrogen atoms. In so doing, Heitler and London did indeed become the first scientists to publish an application of this type.

The German colleagues also incorporated Werner Heisenberg’s ideas on exchange energy. Heisenberg had theorized that the electrons of two given atoms would find themselves attracted to the positively charged nuclei of their atomic pairs. As such, a chemical bond, according to this theory, consisted simply of two electrons jumping back and forth between two atoms, belonging simultaneously to both and to neither.

Heitler and London extended this idea, proposing that chemical bonds sourced their lengths and strengths from the amount of repulsion extant between two positively charged nuclei. The balance between the electrons’ attraction to these nuclei, coupled with the quantifiable repulsion existing between the two nuclei, ultimately served to create the bond.


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Pauling on the precipice of greatness, 1928.

Invigorated by the promise of competition, Pauling set to work applying Heitler and London’s theory to more complex molecules. In part to motivate himself, but also to ensure that he received recognition for his research, Pauling announced in the Proceedings of the National Academy of Sciences that he believed he could solve the tetrahedral binding of carbon using the ideas put forth by quantum mechanics.

This declaration piqued significant interest throughout the scientific community, striking a nerve for chemists and physicists alike, both groups of whom had been puzzling over this specific structure in different ways. On one hand, physicists believed that carbon should have a valence of two because, of its six electrons, four were located in two different subshells. Both sets of two would then be expected to pair off with each other, leaving only two electrons logically available for bonding. On the other hand, chemists found in the laboratory that carbon typically offered four electrons for bonding in nature. In essence, both theory and experiment indicated that neither party was completely right, but so too could neither point of view be completely wrong. Pauling believed that quantum mechanics could illuminate the paradox.

In addition to his theoretical study, Pauling’s extensive graduate training in x-ray crystallography strengthened both his interest in and his flair for atomic structure. By 1928, after a busy year of research, he had established five principles for determining the structure of complex covalent and ionic crystals, later dubbed “Pauling’s Rules.” He used these rules to predict models for particular molecular structures, and then worked backward from the theoretical model to develop a more concrete picture based on x-ray data. When a colleague remarked that this technique resembled the Greek stochastic method – an approach based largely on applied guess work – Pauling offered a correction, stating that

Agreement on a limited number of points cannot be accepted as verification of the hypothesis. In order for the stochastic method to be significant, the principles used in formulating the hypothesis must be restrictive enough to make the hypothesis itself essentially unique.

In other words, Pauling was relying on his knowledge of chemical principles to develop meticulous and educated hypotheses that he could go back and prove. And as he would hasten to add, he placed very little stock in luck or guesswork.


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As work moved forward, Pauling added his rules to three others that had been established by G.N. Lewis – and then expanded and formalized by Heitler and London – concerning the electron pair bond. These rules set parameters for the circumstances in which an electron would be theoretically available to form a chemical bond.

Though equipped with a solid toolkit of his and others’ making, it ultimately took Pauling almost three years to solve the carbon tetrahedron, with his big breakthrough coming in December of 1930. Inspired by the work of MIT physicist John C. Slater, Pauling found a way to reduce the complexity of the radial wave function, a component of bond orbital theory the application of which had been giving him some trouble. With this solution in hand, the math required for solving further steps of the carbon puzzle became significantly more manageable.

Pauling’s subsequent equations led him to develop a model for the structure that consisted of four equal orbitals oriented at the angles of a tetrahedron. Using these equations, Pauling further discerned that the strength of the bonds within the structure increased in accordance with greater degrees of orbital overlap between two atoms. The overlap, Pauling found, produced more exchange energy and this in turn created a stronger bond.

Pauling sent his paper to the Journal of the American Chemical Society (JACS) in February 1931. In it, Pauling detailed three rules governing eigenfunctions that complemented G.N. Lewis’ rules about electron pairs. Pauling used this collection of guidelines to explain relative bond strength, finding that the strongest bonds occurred on the lowest energy level and where orbitals overlap. He also developed a complete theory of magnetic moments and ended the paper stressing the important role that quantum mechanics had played in his formulation of the rules and theories expressed in the work.

The paper, titled “The Nature of the Chemical Bond: Application of Results Obtained from the Quantum Mechanics and from a Theory of Paramagnetic Susceptibility to the Structure of Molecules,” was accepted and published in record time. The subject matter was so new and the ideas so fresh that Arthur Lamb, the editor of JACS at the time, had trouble finding a group qualified enough to review it. Even so, he scheduled the article for the April issue and in so doing published Pauling’s paper a mere six weeks after he had received it.


In 1926, whether he knew it or not, Linus Pauling embarked down a path toward the transformation of chemistry and the way that it would be studied for generations to come. The ideas that he began developing during this time gradually became the standard model for those studying chemistry while simultaneously launching Pauling to dizzying heights. His April 1931 paper, the first in a series of seven, also became the basis for his 1939 book, The Nature of the Chemical Bond, which was almost immediately recognized as a classic of twentieth-century scientific writing.

Largely on the strength of the April JACS article, Pauling also received the 1931 Langmuir Prize from the American Chemical Society, and used the money that came with the prestigious award to further his research. Now that he was interested in molecular structure, he saw it’s promise everywhere within a rapidly expanding research program. In fact, the chemical bond work of the late 1920s and early 1930s laid the foundation for his subsequent program of hemoglobin research, which in turn led to his sickle cell anemia discovery almost twenty years later. In hindsight, it is easy to see how Pauling could have looked back on the achievements of early 1931 as being “the best work I’ve ever done.”

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“The Best Work I’ve Ever Done”

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Linus Pauling, 1931.

[An examination of Linus Pauling’s first paper on the nature of the chemical bond, published in April 1931. This is part 1 of 2.]

“It seems to me that I have introduced into my work on the chemical bond a way of thinking that might not have been introduced by anyone else, at least not for quite a while. I suppose that the complex of ideas that I originated in the period of around 1928 to 1933 – and 1931 was probably my most important paper – has had the greatest impact on chemistry.”

-Linus Pauling, 1977

One of the major film documentaries chronicling Linus Pauling’s life was produced for the long-running NOVA series in 1977. By that point, when asked to look back over the decades of significant work that he had done, Pauling still singled out his insights into the chemical bond as being his most significant contribution to chemistry.

Pauling’s initial 1931 paper in particular marked the first time that he published his revolutionary point of view related to the chemical bond, and reflecting on that period Pauling went so far as to call the article “the best work I’ve ever done.” Indeed, the paper marked the first instance in which Pauling began to spell out the ways in which the burgeoning field of quantum mechanics might be applied to fundamental questions in chemistry. And though first in a lengthy series, Pauling placed major significance on this one paper because it profoundly changed the course of his career and set into motion a period of heavy influenced on the trajectory of an entire discipline.


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G.N. Lewis, ca. 1930.

While an undergraduate at Oregon Agricultural College, Pauling had been taught – and went on to teach his own students – the “hooks and eyes” theory of chemical bonding. In this model, each atom was presumed to have a certain number of hooks or eyes that determined how and to what other atoms it could connect. Though it prevailed at the time, the model was deemed to be outdated and insufficient by many of Pauling’s contemporaries, some of whom were concurrently searching for a more satisfactory replacement.

That said, “hooks and eyes” did serve as a useful precursor to the later concept of valence, because it correctly assumed that each atom possessed a concrete number of electrons to contribute to the formation of bonds with other atoms. The theory also suggested that there were rules governing how chemical bonds worked and how likely it was that two or more atoms might form a bond.

While Pauling was still a student in Oregon, he avidly read G.N. Lewis’ ideas about electron structure and also studied Irving Langmuir’s theory of valence, a tutelage that helped propel his own nascent interest in chemical bonding and atomic structure. Lewis proved to be particularly important. A chemist at the University of California, Berkeley and a future mentor of Pauling’s, Lewis proposed that eight electrons provided a maximally stable environment for a molecule, a tenet known today as the octet rule. Working from this idea, Lewis hypothesized that an atom containing, for example, seven electrons would bond more readily with an atom containing nine electrons, and that the bond that was formed consisted of the electron shared between the two atoms.

Lewis wasn’t the first to chase the nature of the chemical bond. Indeed, the problem had been under attack for a few decades. In 1911, Ernest Rutherford created the first modern atomic model, but ran into trouble because it wasn’t compatible with classical physics. Niels Bohr then updated this model. Less than twenty years after J. J. Thompson had discovered the electron, Bohr suggested that electrons orbited the nucleus in a predictable way, emitting quanta when they moved into lower orbits.

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Arnold Sommerfeld, 1928.

From there, others sought to fill gaps in Bohr’s model. In 1915, Arnold Sommerfeld, a physicist with whom Pauling eventually worked, helped to devise what came to be known as the Sommerfeld-Wilson quantization rules. These guidelines provided an explanation for angular momentum by describing electron orbits as ellipses rather than perfect circles.

At the same time, Werner Heisenberg, Erwin Schrödinger and Max Planck (among others) were rapidly embracing a new way to look at physics, expanding the theory and mathematics behind involved in this innovative approach. In 1925, a year before Pauling began an influential trip to Europe, Heisenberg had authored his “Quantum Theoretical Reinterpretation of Kinematic and Mechanical Relations,” which many point to as the true beginning of quantum mechanics. Schrödinger then completed his wave function in 1926. By contrast, the Lewis and Langmuir models were part of an old system that – as soon Pauling discovered – was in the process of being discarded.


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Linus Pauling at the Temple of Neptune, Paestum, Italy, during his legendary Guggenheim trip to Europe. This photo was taken by Ava Helen in April 1926.

An admirer of Sommerfeld’s work, Pauling traveled to Europe on a Guggenheim fellowship to learn as much as he could about quantum mechanics, which at the time was referred to as “new physics.” He was especially keen to learn more about Schrödinger’s equation and to dig into the ways in which the wave function might be applied to a more sophisticated understanding of the chemical bond. Though impressed by Heisenberg, Pauling gravitated toward Schrödinger because he saw more potential for practical application of the wave function, as opposed to Heisenberg’s matrix mechanics. In a note penned during his travels, Pauling wrote specifically that

I think that it is very interesting that one can see the [psi] functions of Schrödinger’s wave mechanics by means of the X-ray study of crystals. This work should be continued experimentally. I believe that much information regarding the nature of the chemical bond will result from it.

These thoughts proved prophetic, as we will see in part 2 of this series.


Pauling returned to Pasadena in the fall of 1927, bursting with new ideas. While he was away, Caltech chemistry chief A.A. Noyes had sent word that a unique position had been created for his promising young faculty member, one that lined up nicely with Pauling’s new interests. Upon his re-arrival at Caltech, Pauling was to begin working under the title of Assistant Professor of Theoretical Chemistry and Mathematical Physics.

Although Noyes eventually dropped the physics course from the appointment, Pauling liked the idea of hybridizing his interests into one name. It was at that point that he began referring to himself as a quantum chemist.

Advocating for Polyspheron Theory Over Two Decades

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[Part 2 of 2]

In the mid-1960s, as he continued to develop his close-packed spheron theory of atomic nuclei, Linus Pauling sought to use the techniques of creative visualization that had served him so well in his past theoretical work. The situation was trickier this time however, as the discipline of nuclear physics had not yet put forth a single agreed-upon understanding of molecular structure on which a visual model might be built. Rather, as Pauling put it:

There are now two ways of considering the structure of a molecule. One of these ways is by application of a highly refined set of ideas about chemical bonds that was largely developed during the period from 1860 to 1900, and was then significantly extended between 1925 and 1935 through consideration of the empirical information about molecular structure in light of basic principles that were introduced by quantum mechanics.

The second way of considering the structure of a molecule is by solving the wave equation for the molecule, describing the state of the various electrons interacting with one another and with the nuclei.

Both methods had been used since quantum mechanics entered the mainstream in the 1920s and began being applied to topics in chemistry. But according to Pauling, very little effort had been made to develop an empirical theory of the structure of atomic nuclei that corresponded nicely with contemporary ideas on chemical structure. The wave equation approach was further complicated by the fact that, by the mid-1960s, reliable quantum mechanical calculations could be carried out for only a small number of molecules.

In Pauling’s estimation, the most useful attempt to date to develop a workable theory was folded into a discussion that conceptualized light nuclei as aggregates of alpha particles – particles that Pauling renamed “helions” and made a centerpiece of his theory. To address the perceived need to move forward with this mode of thinking, Pauling developed his own conceptual framework and promoted it throughout the 1960s.


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Notes from Pauling’s second Robbins Lecture, February 25, 1966

In 1966 Pauling used his platform as Pomona College’s first Robbins Lecturer to begin spreading a more popular word of this theory — he gave five lectures on the subject in February and March of that year. In 1967 he delivered three more talks on the theory, this time at Princeton University under the auspices of the Plaut Lectureship, an honorific which Pauling was again the first person to occupy. Finally, in 1971, he offered a free public lecture at the University of Colorado, Boulder, promoting his theory as the E.U. Condon Chemical-Physics Lecturer.

Throughout all of this public outreach, Pauling continued to draw up new manuscripts for publication on the topic. In these, he began considering how nuclear wave functions and magnetic-moment values could all be accounted for using polyspheron theory. He also continued to emphasize the compatibility of his ideas with the shell and cluster theories that had gained traction within the discipline.


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A figure included with Pauling’s 1976 manuscript submission to Physical Review

Pauling’s fight to push polyspheron theory into the physics mainstream continued in 1976, by which time the term “helion” was generally being used by nuclear physicists to refer to a Helium-3 nucleus. This common understanding proved disadvantageous to Pauling, as he had defined the term as referring instead to alpha particles (although, interestingly, Pauling had earlier pointed out that “his” helions were notably present in Helium-3).

But there was also good news for Pauling: by now, scientists using electron scattering techniques to investigate the electromagnetic properties of atomic nuclei with prolate deformation were publishing data that seemed to support his point of view. In particular, these experiments had derived information about the shapes of the deformed nuclei that showed what appeared to be the formation of spherons out of the objects defined by polyspheron theory as “helions” and “tritons.”

Pauling almost immediately pounced on this encouraging data, writing a paper initially titled “Comment on the Shapes of Deformed Nuclei,” and then later more forcefully retitled as “The Predication of the Shapes of Deformed Nuclei by the Polyspheron Theory.” He submitted his manuscript to Physical Review in Spring 1976, arguing that reports from current nuclear physicists had confirmed many of his model’s assumptions and that, accordingly, polyspheron theory merited wider acceptance within the field.

The referee overseeing Pauling’s manuscript asked that he make several revisions prior to publication. One major request was that Pauling reshape some of the terminology that was so specific to his theory, due to its confusing nature with respect to broader accepted nomenclature. The journal also asked that Pauling support his claims with clearer and more substantial calculations.

Pauling responded that the journal’s editors had apparently misunderstood the purpose and the importance of his work, and then appended a more substantive introduction to the beginning of the paper to clarify some of the specifics that had been requested of him. When the journal later asked Pauling to remove the extended introduction he refused and his submission was withdrawn. In 1982, some six years later, a paper with the same title finally made it into print by way of the Proceedings of the National Academy of Sciences, a journal that had historically published most submissions authored by distinguished Academy members, among whom Pauling could certainly count himself.

In 1987 Pauling again attempted to advocate on behalf of his theory, writing a new paper titled “Properties of the High-Spin Superprolate Structure of 15266Dy86 are Explained by the Polyspheron Theory.” This paper once more claimed that his now thirty-year-old theory was being steadily confirmed by contemporary laboratory research.

As in 1976, the 1987 manuscript was also rejected, this time by Physical Review and by Nature alike. Seven years later, right around Pauling’s ninety-third birthday, an article with a far less forthright title did appear, once again in PNAS: “Analysis of a Hyperdeformed Band of 152 66 Dy86 on the Basis of a Structure with Two Revolving Clusters, Each with a Previously Unrecognized Two-Tiered Structure.”


Despite his periodic appeals to the practicality of his theory over the course of several decades, and disregarding his insistence that the theory had been vindicated by its prediction of novel discoveries, Linus Pauling’s ideas on polyspherons were never generally accepted by his peers in either physics or chemistry.

Today the utility of Pauling’s model of the atomic nucleus remains in doubt. What does seem to be clear is that he did not succeed in grasping one of the scientific world’s most elusive holy grails: a unified theory of quantum physics and chemistry.

Linus Pauling’s Polyspheron Theory

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[Part 1 of 2]

“I consider the polyspheron theory to be a simple statement about the insight into nuclear structure that is provided by the experimental data and to some extent by the quantum mechanical calculations.” 

– Linus Pauling, 1976

In the early twentieth century, when physicists were gaining knowledge of the properties of atomic nuclei in strides, the still young field of quantum mechanical theory was being used to interpret experimental data. At the same time, chemists were beginning to explore the implications of quantum theory as it pertained to molecular structure, a trend that culminated in Linus Pauling’s groundbreaking book, The Nature of the Chemical Bond, published in 1939.

In the following forty years however, no single theory of the structure of the atomic nucleus emerged that could conceptually account for all the results that chemists and physicists were observing. Nor was there a satisfactory theory that could link the behavior of the most infinitesimal and internal parts of the atom with the much larger scale of molecular behavior and chemical reactions. In other words, there was not yet a single accepted unified theory of quantum physics and chemistry. The pursuit of just such a theory stood as a holy grail of sorts, occupying the hopes, dreams and energy of many a twentieth century scientist.

For parts of five decades, Linus Pauling strove to develop just such a theory, one that could account for the basic structural tendencies and behaviors of the atomic nucleus and prove useful not only for atomic physicists but also for chemists. His efforts resulted in what he called “close-packed spheron theory,” simplified later as “polyspheron theory.”


Though he had begun work on the topic much earlier, Pauling first revealed his theory to the world on October 11, 1965 at a meeting of the National Academy of Sciences, held at the University of Washington in Seattle. His talk that day was titled “The Close-Packed-Spheron Theory of the Structure of Nuclei and the Mechanism of Nuclear Fission,” and its contents mirrored a pair of similarly titled papers that he published that same year: “The Close-Packed-Spheron Theory and Nuclear Fission,” published in Science, and “The Close-Packed-Spheron Model of Atomic Nuclei and Its Relation to the Shell Model,” which appeared in the Proceedings of the National Academy of Sciences.

In each of these works, Pauling advanced a theoretical framework that incorporated features of three older theories – the cluster, shell and liquid-drop theories – while also accounting for several observed phenomena of atomic nuclei that were difficult to explain at the time, such as asymmetric nuclear fission. Importantly, the close-packed spheron model of the nucleus differed from past models by declaring “spherons” as its units, rather than nucleons. Pauling described his rationale for this choice as having been an outgrowth of his thinking about nuclear fission.

Twenty five years ago a phenomenon of tremendous importance was discovered, nuclear fission. In the uranium nucleus and other heavy nuclei, fissioning produces a lighter and a heavier nucleus, with mass ratio about 2/3, several hundred times as often as two nuclei with equal mass are produced.

Why is fission asymmetric in this way? Here is a simple reason why this might be: I assume that in nuclei the nucleons may, as a first approximation, be described as occupying localized 1s orbitals to form small clusters. These small clusters, called spherons, are usually helions, tritons, and dineutrons: in nuclei containing an odd number of neutrons, a (Helium-3) cluster or a deuteron may serve as a spheron.

Pauling’s basic assumption here was that, in atomic nuclei, the nucleons were in large part aggregated into clusters that are arranged as closely as allowed by the laws of physics. Nuclei with more neutrons than protons were called tritons or dineutrons by Pauling. Likewise, the clusters of neutrons and protons occupying localized 1s orbitals were called spherons.

The most important spherons in Pauling’s conception were aggregates of two neutrons and two protons, which he called helions, though they were already known to physicists as alpha particles. The localized 1s orbitals that these spherons occupied could also be described mathematically as hybrids of the central-field orbitals that are outlined in shell theory. This process of hybridization of orbitals provided a formal basis for relating the cluster model – of which Pauling’s theory was an extreme version – and the shell model.

Pauling also put forth the idea that the spherons in a nucleus were arranged in a series of concentric layers. For a large nucleus, the outer part of the cavity inside the surface layer was occupied by spherons that were in contact with the inner side of the surface layer. These spherons constituted a layer of their own, within which Pauling believed there might reside yet another layer of spherons. To avoid confusion with the “shells” of the shell model, Pauling referred to his spheron layers as follows: “the mantle” for the surface layer, and the “outer core” and “inner core” for the two additional constituents of a three-layer nucleus.

In an effort to assure the scientific rank and file that he was not seeking to upend their entire understanding of nuclear physics, Pauling promised that the quantum mechanical calculations enabled by his polyspheron theory were essentially the same as those that had been made using various other models in the past.

Perhaps unwittingly, this assurance left many colleagues within the field wondering why Pauling was bothering to develop this theory at all. For many physicists, Pauling’s work seemed redundant, or perhaps merely an attempt to change the names of existing terms to new ones that fit more elegantly into Pauling’s conceptual framework of atomic structure.

Pauling countered this skepticism by suggesting that both qualitative and rough quantitative conclusions could be drawn from his model without the aid of extensive calculations. If these conclusions agreed with the experimental evidence, Pauling argued, then detailed calculations of this sort might not always be required in the future, pushing scientists just that little bit closer to the discovery of their holy grail.

Leaving La Jolla

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Ava Helen and Linus Pauling near the beach at La Jolla, 1969.

[Pauling at UCSD, part 3 of 3]

In early 1969, Linus Pauling announced that he had accepted an appointment at Stanford University, and that he would be leaving the University of California, San Diego, where he had been on faculty for the past two academic years. In making this announcement, Pauling explained his feeling that Stanford would be a better fit for his orthomolecular research, in part because of the Palo Alto school’s well-established department of psychiatry. (Stanford was also significantly closer to the couple’s home at Deer Flat Ranch, which pleased Ava Helen Pauling immensely.)

Though Pauling and his colleagues had made significant progress on their psychiatric studies at UCSD, one problem that they had yet to conquer was the ability to control for other variables – especially those introduced by diet – that could contribute to variations in the levels of nutrients observed in test subjects’ bodies. Because of this, the group was not able to accurately track what Pauling called “individual gene defects.”

Moving the project to Stanford meant that the researchers would be afforded the opportunity to work with mental health patients at Sonoma State Hospital, all of whom were consuming the same diet, as provided by the Vivonex Corporation. Intrigued, Pauling coordinated with Vivonex to obtain copies of the diet that the company had tailored, the idea being that his control group could follow it as well.

By now, Pauling and his team felt confident that they had uncovered evidence of abnormal patterns of ascorbic acid elimination in individuals suffering from acute and chronic schizophrenia. He and his colleagues planned to continue their analyses of these abnormalities as they moved toward the identification of genetic defects, the creation of diagnostic tools, and the promotion of effective therapies for sufferers of mental disease.


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San Francisco Chronicle, May 27, 1969

Pauling’s final act at UCSD was appropriately radical. Shortly after the student occupation of People’s Park at UC-Berkeley and the subsequent death of James Rector, a Berkeley student who was shot by Alameda County Sherrifs in May 1969, UCSD students and faculty gathered to decide how they would respond to the tragedy at their sister school. Most of the faculty in attendance expressed a desire to simply mourn the death and voice their solidarity with Berkeley, but not to disrupt daily operations.

Pauling, on the other hand, stood in front of the hundreds of students who had gathered and encouraged them to go on strike in protest of recent actions taken by the National Guard, the police, and Governor Ronald Reagan. In so doing, Pauling claimed that the violence at Berkeley was

part of a pattern—the pattern of the war in Vietnam, the increasing militarism of the United States, the growth of the military-industrial complex, the suppression of the human rights of young men and others.

He further explained that those who held power would do whatever was necessary to protect and move forward with a deeply cynical plan. And in detailing his point of view, Pauling made it clear where he stood with regard to the next appropriate actions.

The plan is the continued economic exploitation of human beings. The purpose of the plan, which has been successful year after year, is to make the rich richer and the poor poorer…Everyone in the whole University of California, all the students, the faculties, the employees, should strike against the immorality and injustice of the act at Berkeley.

Less than a week later, Pauling participated in a march and rally at the State Capital in Sacramento, where he gave an impromptu speech that echoed his remarks in San Diego. “The university is not the property of Governor Reagan and the other regents,” he exhorted. “We must protest until the police and the National Guard are removed from the campus of the University of California…the university belongs to us, the students, the faculty, and the people.” So concluded Pauling’s final remarks on the UC system and its regents while a member of the UC faculty.


Although Pauling never worked within the University of California again, his short time at UCSD was undeniably productive and useful. For one, his two years in La Jolla marked a reemergence, of sorts, into the scientific realm following his frustrating tenure at the Center for the Study of Democratic Institutions.

UCSD also provided the opportunity for Pauling to incubate his partnership with Arthur Robinson. This relationship later proved key to the creation of the Institute for Orthomolecular Medicine, known today as the Linus Pauling Institute. The collaboration also provided a strong foundation from which Pauling worked doggedly to expand his research on all manner of topics related to orthomolecular medicine. Though the work ultimately proved to be very controversial, as he left La Jolla, Pauling had every reason to be optimistic about the bold new direction that his research was taking.

Pauling at UCSD: Season of Tumult

 

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[Part 2 of 3 in a series exploring Linus Pauling’s years on faculty at the University of California, San Diego.]

As his program on orthomolecular psychiatry began to take off, Pauling’s work as an activist moved forward with as much zeal as ever. Despite criticism that his association with the Center for the Study of Democratic Institutions (CSDI) and his protests against the Vietnam War made no sense in the context of his scientific career, Pauling had stopped viewing his interests as an activist and his scientific research as being separate branches of a single life.

Pauling happened to be at the University of Massachusetts a mere five days after Martin Luther King Jr. was assassinated. Invited to deliver a series of lectures as the university’s first Distinguished Professor, Pauling fashioned his remarks around the topic of the human aspect of scientific discoveries. Reflecting on the tumult of the previous week, Pauling told his audience that it was not enough to mourn the fallen civil rights leader. Rather, individuals of good conscience were obligated to carry King’s legacy forward by continuing the work that he began.

In keeping with this theme over the course of his lectures, Pauling emphasized the scientist’s responsibility to ensure that discoveries be used for the good of all humanity and society, rather than in support of war and human suffering. Scientific inquiry should also emphasize solutions to current issues, he felt, pointing to the lack of equality in access to medical care in the United States as one such issue. Pauling saw his work in orthomolecular medicine as potentially solving this problem: vitamins were fairly inexpensive, more accessible, and could, he believed, significantly improve one’s mental and physical well-being.


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Notes used by Pauling for his talk, “The Scientific Revolution,” delivered as a component of the lecture series, “The Revolutionary Age, the Challenge to Man,” March 3, 1968.

Pauling made similar connections to his work on sickle cell anemia.

Though he was no longer involved in the daily operations of the CSDI, he continued to participate in a public lecture series that the center sponsored throughout his time in San Diego. In one contribution to a series titled “The Revolutionary Age: The Challenge to Man,” Pauling put forth a potential solution to sickle cell disease. As science had succeeded in identifying the gene mutation responsible for the disease, Pauling believed that forms of social control could be used to prevent carriers of the mutation from marrying and procreating. Over time, Pauling reasoned, the mutation would eventually be phased out.

Pauling specifically called for the drafting of laws that would require genetic testing before marriage. Should tests of this sort reveal that two heterozygotes (individuals carrying one normal chromosome and one mutation) intended to marry, their application for a license would be denied. Pauling put forth similar ideas about restricting the number of children that a couple could have if one parent was shown to be a carrier for sickle cell trait.

In proposing these ideas, Pauling aimed to ensure that his discovery of the molecular basis of sickle cell disease was used to decrease human suffering. Likewise, he felt that whatever hardships the laws that he proposed might cause in the short run, the future benefits accrued from the gradual elimination of the disease would justify the legislation.

Partly because he called this approach “negative eugenics,” Pauling came into harsh criticism for his point of view; indeed, his ideas on this topic remain controversial today. In a number of the lectures that he delivered around the time of his CSDI talk, however, Pauling took pains to clarify that his perspective was not aligned with the broader field of eugenics, a body of thought to which he was opposed. On the contrary, Pauling’s focus was purely genetic and his specific motivation was borne out of a desire to eliminate harmful genetic conditions.


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Bruno Zimm. Credit: University of California, San Diego

At the end of February 1968, Pauling turned 67 year old, and the University of California regents used his age as a mechanism to hold up discussions about his obtaining a permanent appointment in San Diego. Sixty-seven, the board argued, was the typical retiring age within the UC system. Moreover, the UC regents were empowered to veto any age-related retirement exceptions and, given his radical political views, Pauling was unlikely to receive any support at all from the group, much less an exception.

One of the stated reasons why the regents harbored concerns about Pauling’s politics was his increasingly strident rhetoric. Pauling frequently commended student strikes and demonstrations, and although he emphasized nonviolence as the most effective means to foster social change, he encouraged students to recognize that authorities may incite violence through tactics of their own. In these cases, he felt that retaliation was justified, even necessary.

Pauling also believed that the regents and their trustees wielded too much power; for him they were part of a system that largely inhibited social progress and took power away from students. For their part, the regents saw Pauling in a similar light: a dangerously powerful radical who was constraining the university’s capacity to grow.

Realizing that, in all likelihood, Pauling was soon to be forced out, his UCSD colleagues Fred Wall and Bruno Zimm began searching for a way to shift the governing authority for his reappointment to the university president, Charles Hitch, with whom Pauling had maintained a positive relationship. After months of negotiations, Zimm succeeded in winning for Pauling a second year-long appointment.

Pauling expressed gratitude to Zimm for his efforts, but the slim possibility of a permanent position at UCSD had emerged as a source of lingering dismay. Looking for a longer term academic home, Pauling began considering other universities that might also provide better support for his research.

Over time, Ava Helen had also found herself frustrated with UCSD and La Jolla in general. In particular, she disliked their rental house and missed their previous home in Santa Barbara, where she had been able to tend a beautiful garden. As 1968 moved forward, the couple began spending more and more time at Deer Flat Ranch, with Ava Helen hinting that she would like to make the ranch their permanent home in the coming years.

David Pressman

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David Pressman, 1937

[Part 6 of 6 in our series exploring Linus Pauling’s work on the serological properties of simple substances, and the colleagues who assisted him in this work.]

After a meeting with Karl Landsteiner in 1936, Linus Pauling began serious investigations into the link between antibodies and antigens, compiling notes for what would eventually become his serological series, a collection of fifteen papers published during the 1940s. Landsteiner had specifically piqued Pauling’s curiosity on the question of the human body’s specificity mechanism – e.g., how could the body produce antibodies tailored to lock onto and fight specific antigens?

Pauling ultimately surmised that the answer lie in the shape of the molecules, and in the type and number of bonding sites. He described this as a “lock and key” mechanism, otherwise termed as molecular complementarity. Throughout this project, which made a significant impact on the modern study of immunology, Pauling enlisted the help of many undergraduate, graduate, and doctoral students, including a promising young scholar named David Pressman.


David Pressman was born in Detroit, Michigan in 1916. He attended Caltech as an undergraduate, studying under Pauling and completing his degree in 1937. He stayed in Pasadena for his doctorate, earning it in 1940. During this time, he became a part of Pauling’s quest to unravel the structure of proteins, and was particularly involved with the antibody and antigen work.

By this point, Pauling and his colleague Dan Campbell felt confident enough in what they had learned about antibody specificity to attempt creating artificial antibodies. Pauling was enthusiastic about the practical application that such an endeavor might promise for physicians. Warren Weaver, Pauling’s primary contact at the Rockefeller Foundation, which was funding the work, cautioned Pauling against becoming overconfident, but still granted him enough money to hire Pressman full-time. Thus began Pressman’s career in immunology.

At Pauling’s request, Pressman stayed on at Caltech as a post-doc, and during this time the two became friends. In 1943, after failing to prove that they could synthesize antibodies, Pauling’s research team changed their focus from understanding the structural components of antibodies and antigens, to looking for the binding mechanism that allowed antibodies to attach to specific antigens through Van der Waals bonds. One outcome of this was their development of the theory of complementarity, a “lock and key” model in which molecules fit together because of the high levels of specificity that they show for one another.

Pressman authored three papers with Pauling during this phase, including a very important one titled “The Nature of the Forces between Antigen and Antibody and of the Precipitation Reaction,” published in Physiological Reviews. In this paper, the researchers discussed the historical significance of immunology within the context of structural chemistry. Speaking of the tradition in which they worked, Pauling and his colleagues wrote that “two of the most important advances in the attack on the problem of the nature of immunological reactions were the discovery that the specific precipitate contains both antigen and antibody, and the discovery that antibodies, which give antisera their characteristic properties, are proteins.”  In this paper, they also theorized that the immune system depends on structural and chemical forces to function.


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Pressman (at right) in the lab, ca. early 1960s.

In 1947, Pressman decided to pursue an interest in cancer research and moved on to the Sloan Kettering Institute in New York City to investigate the use of radioactive tracers as they pertained to cancer treatment.  The West Coast was never far from his thoughts however, and he often wrote back to friends comparing the two regions and asking for information about life in Pasadena. Of his new arrangements he observed, “The mechanics of living take a much greater part of the time in New York, so that I do not have as much time to do as much as I would like to or could do in Pasadena.”

Pressman’s first few years at Sloan-Kettering were difficult, not only because of the nature of the research that he was conducting – a continuation of the research that he started with Pauling – but because he was frequently forced to move both his lab and his residence, a source of continuous disruption for himself and his family. Sloan Kettering had just been established in the early 1940s and wasn’t formally dedicated until the year after Pressman moved there. Though it eventually became one of the nation’s leading biomedical research institutions, Pressman’s early experiences there coincided with institutional growing pains.

Eventually, as the environment at Sloan-Kettering became more stable, Pressman settled in to his position and provided Pauling with regular updates on his progress. The two often traded manuscripts back and forth, and each solicited technical advice from one another on their specific endeavors, which gradually grew further afield as time moved forward. At Kettering, Pressman continued to study antibody specificity and explored the potential use of radioactive antibodies for tumor localization to develop immunotoxins. In 1954, he left New York City for the Roswell Park Institution in Buffalo, remaining there until his death.


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60th birthday greetings sent to Pauling by David and Reinie Pressman, February 1961.

Pauling and Pressman remained in frequent contact for many years, focusing their voluminous correspondence primarily on work that Pressman continued to do as an outgrowth of their time together in Pasadena.  In July 1961, Pressman wrote that he and a colleague, Oliver Roholt, had potentially made a breakthrough with regard to the sequencing of the polypeptide chain associated with the region of specific binding sites in antibodies. He sent his manuscript, “Isolation of Peptides from an Antibody Site,” to Pauling for review prior to submission to Proceedings of the National Academy of Science. Pauling felt that the manuscript had been put together too quickly and challenged Pressman to do better. He annotated the manuscript with numerous suggestions, most of which Pressman adopted. Less than a week later, Pressman sent the manuscript back to Pauling with the corrections and Pauling transmitted it in to PNAS, where it was received favorably.

The late 1960s were a period of great activity and advancement for Pressman. In 1965, he received the Schoellkopf Medal, a prestigious award granted by the Western New York section of the American Chemical Society. In 1967, he became assistant director at Roswell and, in 1968, he published a book, The Structural Basis of Antibody Specificity. By all outside indications, Pressman’s life was going well.


In 1977 however, tragedy struck when Jeff Pressman, David and Reinie Pressman’s son, committed suicide at the age of 33. Jeff was an up-and-coming professor of political science at MIT, where he was well-liked by faculty and students. Up until a few months before his death, Jeff had seemed happy, both with his career and his life at home. In a letter to Pauling, Pressman described Jeff’s descent into depression as sudden, severe, and uncharacteristic. He also documented the events leading up to his son’s suicide, conveying that he and his wife had become increasingly convinced that the responsibility for the tragedy lay at the feet of a rheumatologist to whom Jeff had been seeking assistance for back pain.

Believing Jeff’s back pain to be primarily muscular in cause, the rheumatologist had prescribed Indocin in January 1977. According to multiple sources that Pressman later consulted, Indocin was a mood-changer, so much so that other patients had reported sudden depressive symptoms and, in severe cases, committed suicide a few months after starting the medication. To complicate matters, the rheumatologist had increased Jeff’s dose to a level that few patients could tolerate well, and had done so more rapidly than was advisable. When Jeff began complaining of insomnia, the rheumatologist prescribed two additional medications, both of which had the potential to worsen his depression. Jeff finally stopped taking Indocin, but the effects lingered. Jeff’s wife, Katherine, reported that Jeff had felt increasingly hopeless about his depression, even though he continued to work at MIT up until his death.


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David Pressman’s former secretary, Cheryl Zuber, posing with a plaque mounted in Pressman’s honor at the Cancer Cell Center, Roswell Memorial Institute, 1981.

In the wake of Jeff Pressman’s death, his colleagues at MIT published a collection of political essays dedicated in his honor. The dedication specifically called out Jeff’s commitment to his students and his impact as a teacher. In it, his colleagues wrote, “He cared deeply about public affairs and immersed himself in them because he genuinely felt that government at its best could improve peoples’ lives.”

Nonetheless, the loss took its toll and, for David Pressman, the only source of solace that he could identify was a return to work. In 1978, his focus in the laboratory was on localizing radio-iodinated antitumor antibodies. He later wrote to Pauling about chronic shoulder pain that he was experiencing, as he was aware of Pauling’s vitamin research and was in search of an alternative to the shoulder replacement surgery that had been recommended by his physician. Pauling put forth an argument for a megadose of vitamins, but Pressman was eventually diagnosed with osteoarthritis. By the end of the year, he was slowing down, both in his work and in his correspondence.

Two years later, in June 1980, Pauling received the news that David Pressman had jumped from the roof of Roswell Park Memorial Institute. In a letter to Pauling informing him of her husband’s death, Reinie Pressman cast about for answers. She wrote at length about the health problems that he had been experiencing, including partial hearing loss, prostate trouble, and chronic problems associated with the osteoarthritis in his right shoulder. She also confided that “You were a significant part of Dave’s happier past.” Pauling replied in kind, stating

I was very fond of David. Also, I owe much to him, because of the vigor and effectiveness with which he tackled scientific problems during the eight years that he worked with me. Much of the success of our program in immunochemistry was due to his contribution.