New Insights into Metals and More

Linus and Peter Pauling at Warwick Castle, England. 1948.

[The Paulings in England: Part 3 of 5]

In his lab, a five minute walk from his office at Balliol College (where he was once caught boiling an egg on his electric space heater), Linus Pauling’s research took a turn from the contents of his lectures – intermolecular forces and biological specificity – and he found himself devoting his research time to metal theory. Pauling had planned to revise the index for his newly published freshman text, General Chemistry, during his Eastman Professorship, but couldn’t seem to get metals off his mind.  As he wrote in a letter to his Caltech colleague J. Holmes Sturdivant, “I thought that I would be doing work in connection with my freshman text while in England, but it has turned out that I have devoted all of my time, and presumably shall continue to do so, to work on the theory of metals and intermetallic compounds.”

He was aided in his lab by three other researchers – David Shoemaker, Hans Kuhn, and a young man from Holland, Dr. F. C. Romeyn. Pauling’s circumstances were proving to be highly productive, and in a March letter to Robert Corey, Pauling wrote of the impact that the change of setting was having in stimulating his thoughts:

I have been having wonderful success in my development of a theory of metals. I think that it has really been very much worthwhile for me to get away for this period of time, under circumstances favorable to my thinking over questions and trying to find their solution. The problem of metals has been on my mind for a number of years, and I haven’t been able to leave it alone, so it is a good thing that I have now managed to get it solved.

This new theory of metals was an extension of Pauling’s valence-bond approach to determining the structure of molecules, as initially developed in the late 1920s. Pauling was first exposed to quantum mechanics as an undergraduate at Oregon State University (then known as Oregon Agricultural College) and retained that interest as he transitioned to graduate studies and faculty employment at the California Institute of Technology.

In 1926 Pauling traveled on a Guggenheim Fellowship to study the developing field of quantum mechanics with physicists in Europe, and especially Germany. He brought these new ideas back to Caltech in the form of quantum chemistry, which he used to compute the electronic structures of molecules. This intuitive valence-bond approach was quickly judged a success and had been popular since the 1930s as a simple model for studying the electron dispersal in the bonds between molecules.

But all the while another chemist, Robert Mulliken (recipient of the 1966 Nobel Prize for Chemistry) had been steadily fostering a rival approach: the molecular orbital theory. While the Pauling family enjoyed springtime in Paris at the beginning of April, Pauling and Mulliken met head to head at a conference on Isotopic Exchange and Molecular Structure. There an entire day was devoted to the comparison of the two theories before a group of quantum chemists. Pauling had written earlier that molecular orbitals were confusing to students, but he learned at this meeting that one always has to stay one’s toes: with more mathematics under their belts, advanced chemistry students were increasingly hungry for the more quantitative approach that Mulliken’s theory offered.

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Sometimes ideas come upon the great thinker at surprising times, and Pauling experienced just such a eureka moment during one of his twice-weekly Oxford lectures in February.  As he wrote to Holmes Sturdivant,

I have just had a great stroke of luck. While giving my lecture on Tuesday I suddenly realized that a calculation about resonance energy of metals that I had just made and was reporting contained the key to the strange valence numbers and numbers of atomic orbitals and unused orbitals that have turned up in my theory of valency of metals.

Notes on intermetallic compounds by Linus Pauling, March 1948.

Pauling worked out his ideas on electron theory and the structure of metals and intermetallic compounds through pages and pages of careful handwritten calculations. In looking at each manuscript now, Pauling presents a hypothesis about some aspect of metal theory and then proceeds to calculate, revise, and recalculate until the theory and the experimental x-ray diffraction data line up. For instance, on one day in March, Pauling was exploring intermetallic compounds from several different angles.  He writes “I shall now treat intermetallic compounds, with my new ideas – resonance of bonds when an extra orbital is available, importance of n=1/2, 1/4 etc., concentration of bonding electrons into strong bonds (Zn-Zn, etc as compared with Na-Na) , transfer of electrons with increase in valence.” Hybrid orbitals, bond lengths, and the overall stability of structures were other items on Pauling’s research agenda.

Of course, not every idea is a winner and a few theories led Pauling down the wrong path; in one manuscript Pauling set out to, as he wrote, “consider sp hybridization – how can we set up a secular equation to give the results given by my bond-strength postulate?”  In the end Pauling found that “the ratio does not come out as desired. It is evident that my assumption that the energies can be taken proportional to ‘bond strengths’ is not right.”  Missteps such as these didn’t deter Pauling from pressing on with his research, for as he often said, “The way to have good ideas is to have lots of ideas, and throw away the bad ones.”

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Chemistry boasts its own special language, or nomenclature, and chemists like Pauling are to thank for the terms that make chemical jargon unique. As research advances, sometimes an entire new word is needed to describe an innovative concept. While tackling the nuances of metal theory at Oxford, Pauling wrote to Sturdivant about this very problem.

By the way, I think that we should do something toward improving the nomenclature. For example, coordination number is an awkward and unwieldy expression – we need one short, precise word for this concept. Perhaps ligancy could be used. It would fit in well with ligand and the verb to ligate. We also need some general words to express the bonds between one atom and the surrounding atoms – we now use the word bond to refer both to the electron pair bond that is resonating around among alternative positions and to the fraction of an electron pair bond that is a portion to a particular position. I have also felt troubled about using the word position in this way – to mean the region between two atoms. If we do introduce any change in nomenclature, it must be very well thought out, and must not involve too great a strain on the memory, or too great a departure from the past.

New fields also call for innovations in instrument development and research programs. Pauling was in constant communication with his colleagues back home about new tools that might be constructed to aid the researchers. He admired the Cavendish’s vast x-ray crystallography laboratory and also gained new insights from reading British journals devoted to scientific instrumentation. He would frequently send word back as to how Caltech workers could improve on a complex apparatus such as the specialized cameras for x-ray diffraction of metallic crystals.

Pauling was likewise intrigued by the English system of graduate education, wherein graduate students would take class work completely during the first year and then spend practically 100% of their time on research during the other two years. Pauling was always looking to improve upon existing programs, but as appealing as the English system was, he acknowledged that in implementing it one would run the risk of not knowing whether a student was an apt researcher for their entire first year!

Dorothy Crowfoot Hodgkin, 1910-1994

Linus Pauling and Dorothy Hodgkin, 1957.

[Part 1 of 2]

On May 12, 1910, Dorothy Crowfoot Hodgkin – a renowned X-ray crystallographer and long-time friend of both Linus and Ava Helen Pauling – was born in Cairo, Egypt. In honor of the hundredth anniversary of her birth, today’s and Thursday’s posts will be devoted to the discussion of not only Hodgkin’s life and extensive contributions to the scientific community, but also her friendship to the Pauling family.

Although Dorothy Crowfoot was born in Egypt, her parents were English and she spent most of her childhood in the United Kingdom. When World War I began in 1914, she and her two sisters were taken to England, where they lived for a time with their grandparents. After the war, Dorothy’s mother, who had moved to Sudan from Cairo with her husband in 1916, decided to return to England to be with her daughters. In 1920 the family moved to Beccles, England, and in 1921 Crowfoot entered the Sir John Leman Grammar School. During her time there, her interest in science grew immensely.

In 1928, after spending a year studying Latin and botany, Dorothy began to focus on chemistry at Oxford’s Somerville College, where she quickly became interested in X-ray crystallography. In 1932 Crowfoot left Oxford for Cambridge to work under J.D. Bernal. Two years later she returned to Oxford and after another two years of study was appointed a research fellow there, a position that she held until 1977.  During her time at Oxford, Dorothy supervised the work of many students, including a young Clara Brink, whose papers now reside in the Oregon State University Libraries Special Collections.

In 1937 Crowfoot married Thomas Hodgkin, with whom she had three children.

Throughout her lengthy scientific career, Hodgkin worked with great success on a wide variety of research projects pertaining to molecules such as sterols, vitamin B12 and insulin. She participated in the 1946 meetings that led to the formation of the International Union for Crystallography, and also became a member of various academies and societies, including the Royal Society and the American Academy of Arts and Sciences.

In 1964 Dorothy Crowfoot Hodgkin received her highest decoration: the Nobel Prize in Chemistry “for her determinations by X-ray techniques of the structures of important biochemical substances.” She also received the Order of Merit, the Lenin Peace Prize – for which she was nominated by Linus Pauling – the Copley Medal, and many other awards for her extensive research.

The first mention of Dorothy Hodgkin in the Pauling Papers appears in correspondence dated to 1947. In it, Pauling writes to Dr. H. Marshall Chadwell of the Rockefeller Foundation, asking for advice about Hodgkin, who will be coming to the U.S. in the fall on a grant from the Rockefeller Foundation. Pauling states that he has “known her work very well, and for a long time, and I have been looking forward to meeting her.” Not long after, Pauling and Hodgkin did meet, and they soon began personally exchanging letters. This process lasted essentially for the rest of their lives, and allows for direct observation of their developing friendship.

Letter from Pauling to Hodgkin, October 7, 1953.

Although much of the correspondence between Hodgkin and Pauling relates to research, they often discuss more personal matters. Alongside the numerous letters on Hodgkin’s work pertaining to Vitamin B12 and Pauling’s research on proteins, there are many letters discussing subjects such as health issues – not only their own but also those of their spouses – Pauling’s experience of being trapped on a cliff, and various travel plans – many of which set up visits to each other.

One specific letter of interest from Pauling to Hodgkin is dated September 14, 1955, in which Pauling writes

to congratulate you on the wonderful job that you have done on Vitamin B12. I find it hard to believe, although very satisfying, that the methods of x-ray crystallography can be used so effectively on such a complex molecule.

Hodgkin had begun work with the Vitamin B12 molecule in 1948.

Another interesting letter from Pauling to Hodgkin illustrates the extent to which the scientific viewpoint permeated Pauling’s thinking on a whole host of matters. In his letter dated January 27, 1959, Pauling thanks Hodgkin for a book that she had sent to him – Christopher Hill’s Puritanism and Revolution – and notes that “I have written to Christopher that I think that mad hatters are mad because of mercury poison – felt is made by treating the hair with mercuric nitrate. His chapter 11 is about a mad hatter.”

One last letter of note is written by Hodgkin on October 14, 1974, in which she informs Pauling that she “should be very happy indeed to be an Associate of the Linus Pauling Institute of Science and Medicine.” In this same letter, Vitamin B12 makes another appearance, demonstrating the longevity of her work with the molecule. This time, Hodgkin sends a stereo print of her structure of the Vitamin B12 coenzyme, which she calls “the most important naturally occurring form of the vitamin.”

Hodgkin and Pauling, 1986.

Unfortunately, not every letter between Pauling and Hodgkin comes under happy circumstances. On December 15, 1981, Hodgkin writes to Pauling to mourn the death of Ava Helen, which had occurred on December 7. Some six months later, on June 4, 1982, Pauling writes to Hodgkin in order to express his sympathy after hearing that her husband Thomas had died.

Hodgkin’s leading work in the field of X-ray crystallography made her one of the most decorated and successful scientists of the twentieth century, as well as a pioneering example of the role that women could play in the laboratory. Although a deep interest in science may have initially introduced Hodgkin and Pauling, our brief look at the correspondence between the two shows that their professional relationship quickly evolved into a long-lasting friendship.

Dorothy Crowfoot Hodgkin died on July 29, 1994, twenty-one days before Linus Pauling.

Check back on Thursday for our post on Hodgkin and Ava Helen Pauling, and make sure to visit the Linus Pauling Online portal for more information on Linus Pauling.

Two Years on the Pauling Beat

Today marks the second anniversary of the launching of the Pauling Blog.  In two years we have generated 214 posts, garnered over 63,000 views (not counting those accruing from syndication, which WordPress doesn’t include in its total statistics) and been graced with nearly 7,400 spam comments, most of which, thankfully, have been kept at bay by the good folks at Akismet.

We’re a bit less philosophical today than was the case one year ago, but we do want to take this moment to reflect back a bit.  Our readership has grown substantially over the past year and, as we enter our terrible twos, we figure this is a good opportunity to take another quick look at some writing that many of our readers may have never seen.  Here then, are ten worthwhile posts from the early days of the blog.

1. Visiting Albert Schweitzer:  a review of the Paulings’ trip to Schweitzer’s medical compound in central Africa – in Linus Pauling’s estimation, “one of the most inaccessible areas of the world.”
2. Pauling and the Presidents: the first in a series of three posts on Pauling’s relationship with this nation’s Commanders in Chief and with the office of the Presidency itself.  The other two posts focus on Pauling’s complicated interactions with John F. Kennedy, and with his own brief flirtation with the idea of running for the office himself.
3. Pauling’s Rules: among Pauling’s major early contributions to science was his formation of a set of rules used to guide one’s analysis of x-ray diffraction data in the determination of crystal structures.
4. The Guggenheim Trip: a three-part series detailing Linus and Ava Helen’s adventures as they toured through Europe for a year, meeting major scientific figures and absorbing the fledgling discipline of quantum mechanics.
5. The Darlings: Maternal Ancestors of Linus Pauling:  an entertaining look at the colorful characters residing further down Pauling’s family tree.  We also featured Pauling’s paternal ancestry as well as Ava Helen’s lineage in separate posts.
6. A Halloween Tale of Ice Cream and Ethanol:  Pauling’s typically detailed and ultra-rational recollection of a hallucination experienced late one November night.
7. Clarifying Three Widespread Quotes:  three quotes attributed to Linus Pauling are scattered across the Internet.  This post investigates whether or not Pauling actually authored them.
8. Pauling in the ROTC:  often accused of anti-Americanism due to his pacifist beliefs, few people know that Pauling actually served in the Reserve Officers Training Corps, ultimately rising to the rank of Major.  This post was among the first in our lengthy Oregon 150 series, celebrating Pauling’s relationship with his home state.
9. Mastering Genetics: Pauling and Eugenics:  a post that delves into what was among the more controversial stances that Pauling ever took.
10. Linus Pauling Baseball:  we can’t help it – the video is priceless.

As always, thanks for reading!

David and Clara Shoemaker

David and Clara Shoemaker working in an x-ray laboratory at Oregon State University, 1983.

Husband and wife crystallographers David and Clara Shoemaker were, in many respects, an unlikely couple.

David Shoemaker was born on May 12, 1920 in the tiny town of Kooskia, Idaho. Clara Brink was born on June 20, 1921 in Rolde, Holland. Both moved through their primary studies in orderly fashion and progressed to undergraduate work in chemistry – David at Reed College in Portland, Oregon, Clara at the University of Leiden.

In 1942 David received his bachelor’s degree from Reed and moved directly to the California Institute of Technology. Working under Linus Pauling, David quickly established himself as a promising doctoral candidate. His research was initially divided between Pauling’s expansive program of scientific war work and, later, a series of crystallographic investigations. While in Pasadena, David determined the structure of sixteen molecules, most notable among them threonine, an amino acid.

Upon receiving his Ph. D. in 1947, David – with the assistance of Pauling – was subsequently named a Guggenheim fellow, studying at both Oxford and the Institute for Theoretical Physics in Copenhagen. Aged 27, he was among the youngest of his era to receive a Guggenheim Fellowship.

Group photo of participants at the Conference on Current Problems of Physics. Copenhagen, Denmark. September 1947. Niels Bohr sits in the front row, far left. David Shoemaker is seated in the second row, fourth from right.

Clara’s path through graduate studies was somewhat less smooth. She completed her undergraduate work at the University of Leiden in 1941, shortly before the Nazi occupation of the Netherlands and the subsequent closing of the university. Despite the turbulence of World War II, Clara was able to commence her graduate studies through the University of Utrecht, though much of her coursework was self-taught, conducted in her parents’ home. Despite these handicaps, Clara completed her doctoral examinations on time, in 1946, after which point she assumed an assistantship at the University of Utrecht and learned the techniques of x-ray crystallography, commuting one day per week to Amsterdam to study under the renowned crystallographer Caroline MacGillavry.

The years immediately following the close of hostilities were fruitful ones for both David and Clara. Having returned home from his Guggenheim trip, David was named a Senior Research Fellow at Caltech, where he solved the difficult structure of DL-serine and began the research program that came to define much of his (and Clara’s) career – a broad series of investigations into the structures of complex transition-metal phases. In the meantime, Clara became a full-time crystallographer, first studying crystal structures of monovalent ions at the University of Leiden and later working for one year at Oxford, where she conducted research on the crystal structure of vitamin B12 under Dorothy Hodgkin, the 1964 Nobel laureate in Chemistry.

In 1951 David was hired away from Caltech by the Massachusetts Institute of Technology, where he began investigating zeolite structures as an Assistant Professor. Two years later, dissatisfied with the working environment at the University of Leiden, Clara took a one-year leave of absence to work on transition metals at M.I.T. Her laboratory in Cambridge was run by David Shoemaker.

In 1954 David renewed Clara’s leave of absence for an additional year and by 1955 it was clear that Clara would not be returning to Europe – on August 5th, the couple was married. Shortly thereafter Clara transferred to Harvard Medical School to work under the biochemist Barbara W. Low. One year later, Clara gave birth to the couple’s only son. While caring for the newborn Robert, Clara worked from home on the International Tables of Crystallography.

The Shoemakers enjoyed a productive tenure at M. I. T. – David was promoted to full professor, began a lengthy service on the U. S. National Committee for Crystallography (including a three-year term as President) and published widely, including a textbook titled Experiments in Physical Chemistry, which would eventually run through six editions.

In 1970 David was elected President of the American Crystallography Association. That same year, the Shoemakers relocated to Oregon State University, where David had been hired to chair the Department of Chemistry. In reaction to the university’s nepotism guidelines, Clara arranged to work as Research Associate under Dr. Ken Hedberg – like David Shoemaker, a former graduate student of Linus Pauling. The arrangement lasted for several years until the university’s rules were relaxed.

Model of the crystal structure and superstructure of the K Phase, Mn77Fe4Si19. Model built by Clara B. Shoemaker, David P. Shoemaker and Ted E. Hopkins.

During his tenure as department chair, David oversaw two major building projects – the construction of a new chemistry laboratory facility and the renovation of the chemistry offices and research building. Over that same period of time, Clara trained several graduate students in techniques of x-ray crystallography, publishing papers with many of her protégés. The couple retired in 1984, though they continued to conduct important work on transition metal phases as well as the controversial topic of quasicrystals.

The Shoemakers remained close friends with Linus Pauling, though they did dispute certain of Pauling’s claims about the nature of quasicrystals. In 1995 David Shoemaker, himself in fading health, spoke of his long association with Pauling at a memorial conference organized at Oregon State University. David’s comments detailing his recollection of the discovery of the alpha-helix caused something of a stir in the audience, as the provenance of the alpha-helix work has long been a matter of some dispute.

David Shoemaker on the Discovery of the Alpha Helix

Afterward, Shoemaker offered this clarification:

My memory may have been faulty in claiming to have seen Pauling actually taping his cardboard amide linkages together to form a helix, but Professor William Lipscomb, in a talk that preceded mine, showed a drawing in Pauling’s own hand of an alpha-helix rolled out flat, showing what points the polypeptide chain joined together in the helix. The drawing was titled ‘alpha helix. First drawn March 1948. Linus Pauling.’ My visit to Oxford was from January to March 1948.

David Shoemaker died of kidney failure on August 24, 1995, some six months after the Pauling memorial conference. His wife Clara, a close friend of our department, passed away on September 30, 2009. Over the course of their professional association, David and Clara published thirty-six scientific papers together.

The David and Clara Shoemaker Papers are just one of the many collections held in the OSU Libraries Special Collections.

The Pauling Centenary Conference

The date February 28, 2001 is meaningful to many residents of the Pacific Northwest.  At 10:54 AM that morning, the Nisqually earthquake, a magnitude 6.8 temblor located northwest of Olympia, Washington, shook the earth beneath the greater Seattle-Tacoma area and ultimately caused over $1 billion in damage.

Some 200 miles south in Corvallis, faint signs of the earthquake were noticed.  In the lobby of the LaSells Stewart Center, for instance, observers noted coats on a coat rack mysteriously swaying.  At the time, few thought much of what they were seeing however, given that an important local event (if something short of seismic) occupied the attentions of most.  February 28, 2001 was the one-hundredth anniversary of Linus Pauling’s birth and the LaSells Stewart Center was the site of a day-long conference honoring Pauling’s memory.

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“In 1986, just before [Lloyd] Jeffress died, Pauling wrote him a letter in which he caught him up on the events of the past year. The last paragraph of the letter related a recent article that Pauling had published in Nature magazine, which had stirred up controversy in the scientific community. A reporter had asked Pauling, ‘Do you have a liking for controversy?’ ‘No,’ replied Pauling. ‘I have a liking for the truth.’ This phrase, ‘a liking for the truth,’ and its surrogate implications of Pauling’s passion for discovery, even in the face of controversy, is a theme of this conference, and we hope that you will be enlightened and entertained by what is to follow.”

-Cliff Mead, centenary conference introductory remarks

“A Liking for the Truth: Truth and Controversy in the Work of Linus Pauling” assembled a multifaceted group of speakers who directly and indirectly reflected upon Pauling’s legacy as a scientist, activist and human being.  The day’s keynote speaker was Dr. Ahmed Zewail, the Linus Pauling Chair Professor of Chemistry and Professor of Physics at the California Institute of Technology, and the recipient of the 1999 Nobel Prize for Chemistry.  Zewail’s topic was the evolution of femtoscience, the study of atomic behaviors that occur in very short periods of time, a breathtaking field of research that allows scientists to, in Zewail’s words, “see bonds and atoms.”

Whereas Zewail spoke of time, another of the day’s presentations, by crystallographer and long-time Pauling family friend Dr. Jack Dunitz, focused on space.  Dunitz, Pauling and many others enmeshed in the practice of crystallography shared a deep interest in developing theories governing the rules that underlie “closest-packing” in molecules, work that Pauling and Max Delbrück extended into the realm of biology through their theory of molecular complementarity.

Jack Dunitz at a Caltech graduate student outing, ca. 1948.

Two Pauling biographers were likewise involved in the centenary activities.  Tom Hager spoke eloquently of the real world consequences that enveloped the Paulings as their peace work assumed international prominence.  Dr. Robert Paradowski reflected upon a turbulent period of the Paulings lives as a young couple, as the pair toured through Europe during Linus’s Guggenheim studies in 1926-1927.

Perhaps the day’s most broadly interesting talk, however, was delivered by Linus Pauling, Jr., the eldest of the four Pauling children.  Recalling memories as varied as Christmas traditions, the family cars and an eventful restaurant meal, Linus Jr. shed insight into a world hidden from even the closest of colleagues and most meticulous of biographers.  In the video excerpt below, Linus Jr. recounts the details of a cherished family tradition – regular vacations to the Painted Canyon desert.

Transcribed video of the Pauling Centenary Conference is available here.

The X-Ray Crystallography that Propelled the Race for DNA: Astbury’s Pictures vs. Franklin’s Photo 51

Rosalind Franklin, March 1956

During their so-called race to discover the structure of DNA, Linus Pauling and the unlikely pair of James Watson and Francis Crick utilized remarkably similar approaches in attempting to solve the riddle of the genetic material. In fact, one of the main tactics used by Watson and Crick was to approach the problem in the same manner that they assumed Pauling would. Although Pauling and Watson and Crick did, at one point, come up with nearly identical, yet incorrect, structures, it was Watson and Crick who would eventually solve DNA. Why then, if the pair were thinking like Pauling, were they able to beat him to the structure?

Although there were a variety of reasons behind Watson and Crick’s success, a good portion of it can be attributed to the relative superiority of resources available to them. Watson and Crick obviously had each other to keep themselves in check, but they also benefited from other voices of criticism such as Rosalind Franklin, Maurice Wilkins, and later Jerry Donohue. Linus Pauling also shared his ideas with his colleagues, but none of them were very familiar with DNA, and therefore couldn’t offer much feedback. (And they were largely ignored even when they did offer criticisms of Pauling’s structure.)

Another vital resource available to Watson and Crick was an excellent X-ray crystallography pattern, the famous photo 51, taken by Rosalind Franklin. Although, in all likelihood, Pauling could have also viewed Franklin’s photographs had he tried, he settled on using blurry patterns published by William T. Astbury several years before Franklin’s superior images. These X-ray photographs are the main topic of today’s post. In particular, the factors accounting for the difference in quality between Franklin’s and Astbury’s patterns will be discussed. Before delving into this subject, however, a brief overview of X-ray crystallography is necessary.

William T. Astbury, ca. 1950s.

X-ray crystallography, also sometimes known as X-ray diffraction, is used to determine the arrangement of atoms within a crystalline molecule. It is a rather complicated procedure, and the photos taken in the process can be interpreted only by a person with significant training. The steps to obtaining these photos are as follows.

First, an adequate crystal must be obtained. This is a very difficult step because the crystal must be large enough to observe and also sufficiently uniform. If it does not meet these specifications, errors – such as blurriness – will occur, often rendering the resulting crystallographic patterns useless, at least for purposes of determining atomic arrangement.

After an adequate crystalline specimen is obtained, a beam of X-rays is shined through it. When the beam strikes the electron clouds of the atoms in the crystal, it is scattered. These scattered beams can then be observed on a screen placed behind the crystal. Based on the angles and intensities of the scattered beams, a crystallographer can create a three dimensional picture of the electron density of the crystal.

Finally, from the electron density information, the mean positions of the atoms within a crystal can be determined, and the structure of the molecule can be considered “solved.” That said, just one image is not nearly enough to determine the structure of an entire crystal. Therefore, the crystal must be rotated stepwise through angles up to and even slightly beyond 180 degrees, depending on the specimen. Patterns are required at each step, and complete data sets may contain hundreds of photos.

Clearly, because the process of X-ray crystallography is so cumbersome, there are many opportunities for mistakes that may have led to the poor quality of Astbury’s photographs. However, Astbury’s techniques seem to have been excellent. He was a very experienced crystallographer, and had achieved great success in his earlier work with X-ray diffraction on substances such as keratin.

As it turns out, Astbury’s photos were of poor quality because of the DNA sample he was using. In the early 1950s, Rosalind Franklin had discovered that DNA came in two forms – a dry condensed form and a wet extended form. Astbury’s DNA sample was well prepared from calf thymus, but it contained a mixture of the two forms. This turned out to be the major reason why Astbury’s photographs were so blurry

Astbury's images, from "X-Ray Studies of Nucleic Acids," 1947. Plate 1.

Astbury's images, 1947. Plate 2.

It is important to note that, even if Astbury had known he was using a poor crystalline sample of DNA, he probably still wouldn’t have been able to compete with the quality of Franklin’s photos. In 1950, three years after Astbury’s images were published, Maurice Wilkins developed a way to obtain much better X-ray patterns of DNA through the use of a solution of sodium thymonucleate. This solution is highly viscous, and Wilkins found that thin strands could be drawn out by gently dipping a glass stirring rod into a sample and slowly pulling it out. These thin strands were pure DNA, and Wilkins was able to get excellent X-ray patterns from them.

Before long, Wilkins had also acquired better equipment and had also hired Rosalind Franklin to run it. Franklin, essentially working independently, used the same basic technique developed by Wilkins. She did, however, add several of her own smaller experimental refinements, which made the photographs even better. Eventually, she developed photo 51, which would later be shown to Watson and Crick. The rest, as they say, is history.

Crystallographic photo of Sodium Thymonucleate, Type B. "Photo 51." Taken by Rosalind Franklin, May 1952.

Rosalind Franklin and William Astbury were both excellent crystallographers, but Franklin’s experience with DNA gave her a clear advantage when working with the molecule. Her brilliant X-ray patterns would later prove to be a major determining factor in the “race for DNA”. For more information on DNA, please visit the Race for DNA website. For much more on Linus Pauling, check out the Linus Pauling Online portal.

Pauling’s Methodology: X-ray Crystallography

X-ray apparatus at Linus Pauling's desk, Gates Laboratory, California Institute of Technology. 1925.

“I was very fortunate in having A.A. Noyes suggest to me, or tell me, that I was to work with Roscoe Dickinson on x-ray crystallography, determination of the structure of crystals by x-ray diffraction. This technique gave for the first time detailed information about how atoms are related to other atoms in a crystal and how far apart they are from the other atoms.“
- Linus Pauling, 1988.

As a graduate student, well before Pauling began to research hemoglobin in earnest, he spent a great deal of his time using the technique of X-ray crystallography to determine the crystalline structure of a number of inorganic compounds. Pauling recalled that at that time X-ray crystallography “was a new technique, ten years old when I began. Quite a number of structures had been determined but there was a tremendous field open, a tremendous amount of work that could be done.”

Listen: Pauling discusses the importance of X-ray crystallography to his early structural chemistry research

The young Pauling obviously reveled in the excitement of being able to use a new and powerful technology. “We have a pretty extensive collection of apparatus” he once wrote to William Lawrence Bragg, the senior author of a 1922 textbook that started Pauling on X-ray crystallographic research. Any one of Bragg’s student’s, Pauling remarked, “no matter how physical his training,” need not “be frightened at coming to a chemical laboratory” so well-stocked with mechanical apparatus.

Initially Pauling used the technique of X-ray diffraction to determine the structures of fairly simple inorganic compounds, but later, as his own expertise grew and as he discovered new sources of funding, Pauling oriented this new technology toward complex organic compounds, including hemoglobin.

What was ultimately important to Pauling was not what X-ray crystallography could tell him about the size, structure, or relative placement of atoms within a molecule, but rather, what broader theories that information could then be used to support. His growing allegiance to structural chemistry, his developing ideas about the nature of the chemical bond, and his still nascent interest in biochemical interaction were all fed by his experience of rigorously determining molecular structure through new technological methods.

Pauling’s manuscript notes concerning his early experiments with hemochromogen, for instance, indicate the wide spectrum of experimental results he had to assimilate in order to create a coherent picture of the hemoglobin molecule.

"Outline of Experiments on Hemochromagen," pg. 1. June 25, 1935.

The difficulties presented by the need to combine the information he had obtained from x-diffraction with information from other kinds of experimentation, including solubility and more traditional experimental methods, are readily apparent in Pauling’s notes.  Indeed, the impressive new technology of X-ray crystallography is relegated to just one entry in a list of experimental results.

Ultimately it wasn’t the technology at Pauling’s disposal that helped him become such a successful researcher, but rather his attitude in approaching technology and his ability to use the results it gave him to construct more broadly-applicable and intellectually-powerful theories.

To learn more about Linus Pauling’s use of x-ray crystallography, see the websites Linus Pauling and the Nature of the Chemical Bond: A Documentary History and It’s in the Blood!  A Documentary History of Linus Pauling, Hemoglobin and Sickle Cell Anemia.