The Life of Herman Pauling – Linus Pauling’s Father

Herman Pauling, ca. 1899.

Herman Pauling, ca. 1899.

(Part 1 of 2)

The son of German immigrants, Charles Henry “Carl” Pauling – Linus Pauling’s paternal grandfather – joined his father and brothers during the Civil War by enlisting in Company E of the 45th Regiment of the Missouri Volunteers.  After the war, Carl met Adelheit Blanken, who had come to Missouri with her family from Germany.  They settled in Concordia, Missouri, where they had four children: the youngest, Herman Henry William, was born in 1876.

The following year, the family traveled to Biggs, California where they settled in a predominately German community. It was here where Herman’s sister, Anne Charlotte, was born.  Herman and Anne would be the only two of Carl and Adelheit’s five children to survive into their twenties.

In 1882 the Paulings moved again, this time to Oswego, Oregon, near Portland.  Here Carl worked as an iron monger at the largest foundry west of the Rockies.  It was likewise in Oswego that Herman began to attend grammar school.  By the tenth grade, in 1890, he had grown tired of school and dropped out, talking his way into an apprenticeship with a local druggist instead.


Condon drug store, early 1900s.

Condon drug store, early 1900s.

In the late 19th century, medicine not well regulated, leaving the door open for basically anyone to come along and make whatever claims they wished concerning the efficacy of their products.  The druggist with whom Herman apprenticed taught him to avoid making wild statements and instead instilled in him the importance of the druggist’s responsibility to his customers. This professional ethic was closely bound to the practice of careful preparation of extracts, compounds, ointments, tinctures, oils and other products.  By his nineteenth birthday, after several years apprenticing, Herman felt confident enough to move to Portland, where he found work at one of the largest pharmacies in the city.

The pharmacy, Skidmore Drug Company, employed Herman as a traveling salesman, his purview being a one-hundred mile area ringing Portland; he covered his turf by horse and buggy.  After a financial depression hit the country in late 1893, Herman moved back to Oswego to run his own pharmacy.  The depression led to the closing of Oswego’s massive foundry, pushing many to leave town, including the doctors and other druggists.  Pretty soon Herman found that he was only person in town who could possibly care for the sick and his reputation quickly spread.  The town was grateful for his skills and his caring disposition – as instilled by his mentor – in addition to the low fees that he charged for his consultations.  If he was particularly concerned about them, Herman would commonly visit his patients well after their original appointment, making sure that their health had improved.

Herman’s reputation spread back to Portland as well, and investors there saw him as the perfect person to open up a drugstore in the small eastern Oregon town of Condon. By this time, regulations on drug sales had begun to increase, creating opportunities for those who were well-situated to meet the new standards and get in on the emerging market.


Herman Pauling, 1902.

Herman Pauling, 1902.

Upon first arriving in Condon in the summer of 1899, Herman was not impressed.  The town center consisted of six blocks along Main Street that ran right out into the desert and wheat farms. But by the fall, things began to look up.  Just as in Oswego, his good reputation quickly grew and he became the featured guest at several town functions.  The weekly newspaper, The Globe, described “Doctor” Pauling as “a registered, reliable and experienced druggist.”

He also began to attract the attention of some of the younger women in town.  Goldie Stephenson, the oldest daughter of one of the area’s wealthier families, invited Herman over to her house to meet her sister Belle.  The two immediately hit it off and soon could be seen talking to each other at many of the town’s community dinners and dances.  By Christmas, Herman had proposed to Belle and she immediately accepted.  Herman had business to attend to back in Portland soon after, and so had to be away from his fiancé for a brief time.   This gave him the opportunity to express his love in letters.  In a valentine that Herman wrote to Belle, he confided

Dear love, when life’s storms are raging fiercely I offer you my arms as your protection, and you can trust in their fond yet firm embrace.  When in after years the cares of home and motherhood bear upon your mind you shall find me ever an able assistant and benefactor.

Herman even wrote her a poem:

A maiden fair with jet black hair/ Her heart beats kind and true/ She confides in me her every care/ This maid with eyes light blue.

Herman and Belle married on May 27, 1900 at the Congregationalist Church in Condon.  (Herman was raised as a Lutheran, but was quite willing to adapt to Belle’s Congregationalist upbringing.)  Trouble struck quickly however as, only weeks after the wedding, the Portland investors that had backed Herman’s initial move to Condon pulled out of the venture, leaving Herman scrambling to look for a new job.  Herman had to settle for a clerk’s position at a pharmacy in Portland and the newlyweds found a small apartment near Chinatown.


The young father with his infant daughter, Pauline, and slightly older son, Linus. 1903.

The young father with his infant daughter, Pauline, and slightly older son, Linus. 1903.

Newly married, Herman worked as hard as he could to support his new bride. Meanwhile, the entertainment and shopping possibilities in Portland gave Belle new realms to explore that were unavailable in Condon.  Belle was also pregnant when they arrived in Portland; Linus Carl Pauling, Belle and Herman’s first child, was born at the end of February 1901.  Herman was thrilled to have a son and worked even harder to provide for his growing family.  But this left Belle alone much of the time to take care of Linus on her own.  Only nineteen years old, the young mother was still drawn to the possibilities of the city.  But her feeling of being stuck with the children continued to grow as Pauline was born in August 1902, and Lucile on New Year’s Day 1904.

When Herman was home, he would take Linus for walks around the neighborhood to try to wear out the energetic toddler.  The two wandered through the shops and Herman’s charismatic little boy drew the attention of neighborhood merchants who taught Linus to count to one-hundred in Chinese, a talent that garnered a measure of celebrity for the little boy as he displayed his counting skills for passersby.  Belle sometimes joined Herman and Linus on their walks, and the family often visited a nearby water fountain.

Herman continued to look for a better job and eventually found one in Salem as a traveling salesman for the jeweler and druggist D. J. Fry.  By October 1904, the family had moved into their new house in Salem.  For his job, Herman traveled up and down the Willamette Valley, sometimes seventy miles in one day, still using a horse and buggy.  With Herman away even more, Belle was left to care for the children in another new town, and she quickly made it known that she was not happy with their situation.  In his correspondence with his wife, Herman’s replies are directed at a better future; one where he would own his own drugstore and could provide Belle with more luxury than she had thus far known in their married life.

The Iron-Oxygen Bond in Oxyhemoglobin

Pastel drawing of the hemoglobin molecule by Roger Hayward, 1964.

Part of the beauty of studying the life and work of Linus Pauling is that doing so often affords the opportunity to look at how the science of today has developed from questions that were once unanswered and widely debated. One such question was how hemoglobin, the protein in red blood cells, binds to and releases oxygen as it is inhaled and carried to the body’s tissues.

In 1959, Max Perutz used x-ray crystallography to obtain an image of oxyhemoglobin, a hemoglobin protein bound to an oxygen molecule. This was a major breakthrough in many ways. For one, it allowed chemists to observe an image of a three-dimensional protein found in humans for the first time. The imagery also provided tantalizing hints about the specific chemistry that might explain oxyhemoglobin’s structure.

Unfortunately, creating an image of the molecular structure didn’t solve everything, as Perutz himself would reflect in a 1978 article, “Hemoglobin Structure and Respiratory Transport.”

We were like explorers who have discovered a new continent, but it was not the end of the voyage, because our much-admired model did not reveal [hemoglobin's] inner workings.


The Joseph Weiss Medal, which commemorates his work as a radiation chemist.

The Joseph Weiss Medal, which commemorates his work as a radiation chemist.

Perutz’s work naturally incited biochemists to further explore the structure of hemoglobin. While it was known that the oxygen-carrying heme group in hemoglobin is composed of nitrogen, carbon, and an oxygen-binding iron, there was much debate over what kind of bond could cause the union and dissociation of these elements.

In 1964, Joseph Weiss, a professor at Newcastle University in England, attempted to answer the question of what specific bond forms between iron and oxygen. Weiss’s conclusions were published in a 1964 article, “Nature of the Iron–Oxygen Bond in Oxyhæmoglobin”.

According to Weiss, the iron in hemoglobin would need to be in the ferric state (iron with an ionic charge of +3) in order to account for hemoglobin’s behavior in oxygen transport.  He believed that ferric iron would also explain hemoglobin’s spectroscopy (the wavelengths of light reflected by a  molecule). Pauling, however, disagreed with Weiss.


Pauling, Max Delbruck and Max Perutz, 1976.

Interestingly, Pauling had been looking into the subject of the iron-oxygen bond in hemoglobin since 1948, when he presented a paper titled “The Electronic Structure of Hemoglobin” at a symposium in Cambridge, England. Pauling’s presentation considered advances in x-ray diffraction and quantum mechanics to propose a structure for the heme group in the protein. Unlike Weiss, Pauling believed that the iron-oxygen bond in oxyhemoglobin would require ferrous iron (an iron with an ionic charge of +2) to form a double bond (a bond involving two electrons) with oxygen as it was being transported throughout the body.  Weiss’s paper did little to change Pauling’s mind on the subject.

In 1964, Pauling wrote “Nature of the Iron–Oxygen Bond in Oxyhæmoglobin,” a direct response to Weiss’s article with the same title. In it, Pauling stated

I conclude that oxyhæmoglobin and related hæmoglobin compounds are properly described as  containing ferrous iron, rather than ferric iron, that their electronic structure involves essentially the formation of  a double bond between the iron atom and the near-by oxygen atom in  oxyhæmoglobin

Pauling’s interest in the components of blood had emerged early on in his career. In 1948 he suggested using hemoglobin to test his earlier ideas about bonds that had remained unexplored, as the structure of the protein had been hitherto not fully understood. This was a pursuit that he in which he strongly believed: in his Cambridge talk, “The Electronic Structure of Hemoglobin,” he had concluded that

even the great amount of work that would be needed for a complete determination of [hemoglobin's] structure, involving the location of each of the thousands of atoms in its molecule, would be justified.

Many years later, in his 1992 article “The Significance of the Hydrogen Bond,” Max Perutz stated that that Pauling’s words, as published in 1949, were among the inspirations propelling his own work a decade later.


“The Electronic Structure of Hemoglobin” wasn’t the only publication by Pauling that inspired Perutz. In 1970, he used Pauling’s “The Magnetic Properties and Structure of Hemoglobin” to further his own study of the structure of hemoglobin, work which finally led to the discovery that the iron-oxygen binding in hemoglobin depends on the electronic spin transition of the iron atom.

Essentially, Perutz found that when the ferrous iron in hemoglobin is in a low spin state, its higher d-orbitals are unoccupied by electrons, which allows oxygen to form a bond with iron. In a high spin state, the electrons in ferrous iron are occupying all d-orbitals in the atom and oxygen remains unbound.

This suggests that the more likely structure for hemoglobin involves a single bond between iron and the oxygen molecule, not the double bond that Pauling had proposed in 1948 and again in 1964.  But Pauling was correct with respect to the presence of ferrous iron in the compound, and he had been able to make this determination before any crystallographic pictures were available to him.

 

The Bellingham Suit

bellingham-newsclip

From the years 1960 to 1968, Linus Pauling either threatened or actually instigated several libel suits against various newspapers and media outlets throughout the country, demanding retractions and financial compensation for defamatory statements issued about him. The damaging statements usually stemmed from Pauling’s hearings before the Senate Internal Security Subcommittee in 1960, during which the inquisitors grilled Pauling about his activities in the peace movement, especially his 1958 nuclear bomb test petition, and repeatedly implied that he was a communist sympathizer.

Pauling was not a communist and, in fact, had led a large research effort on behalf of the U.S. war effort during World War II, work for which he earned several commendations, including the Presidential Medal for Merit. So naturally, Pauling was very frustrated when newspapers around the country began to question his loyalty to the US, and he became increasingly alarmed as his reputation was attacked amidst the heightened tensions of the Cold War era.

One of the first newspapers to provoke legal action from Pauling was the Bellingham, [Washington] Herald. In late November and early December 1960, shortly before and after Pauling gave a talk at Western Washington College, the paper published five letters to the editor attacking Pauling. The letters contained factually incorrect information, such as the suggestion that Pauling had appeared before the House Un-American Activities Committee (rather than the Senate Internal Security Subcommittee) and that he was a communist. The letters also accused him of other communist-related activity that had never been proven by the Senate Internal Security Subcommittee.

In early December, Pauling wrote to the newspaper demanding a retraction of the letters that it had published. The Herald responded quickly, printing a note explaining that they were “unable to substantiate the claims” of one letter published on December 2nd by Martin Gegnor.  That stated, the editors ended their note by declaring that “it is the policy of this newspaper to give free expression to our readers.” They likewise noted that the Herald, in its December 2nd issue, had also printed a long letter from the wife of the president of Western Washington College extolling Pauling’s scientific achievements.

Pauling was not satisfied with the Herald’s response and wrote a second letter to the paper that was published on December 20th. This letter went to great pains to point out how each defamatory statement issued about him was untrue. Although the Herald published Pauling’s letter, they did so while emphasizing that it was his viewpoint and that the paper did not explicitly apologize for its previous actions. This upset Pauling, who suspected that Martin Gegnor was not actually an ordinary resident of Bellingham, Washington but was instead a pen name for another author, possibly a journalist at the newspaper. (A suspicion that was, many years later, proven correct.)


ubc-students-lp

Pauling decided to sue the Bellingham Publishing Company and the letter writers for libel. He later dropped his case against the individuals and decided to focus entirely on the newspaper, which he sued for $500,000. Pauling complained that the allegations in the letters were untrue and that he had no communist tendencies. He also claimed that damages to his reputation might result in the loss of royalties from his three textbooks, which amounted at the time to about $40,000 per year.

In December 1961, the judge overseeing the suit ordered Pauling to release the names of the people who had helped to circulate his nuclear bomb test petition. This very information had been requested of Pauling by the Senate Internal Security Subcommittee in the summer of 1960. Rising contempt of Congress, Pauling had refused to turn it over, fearing that the reputations of his associates would be smeared once their names came to light. This time around, Pauling looked to his Seattle-based lawyer, Francis Hoague, for advice. Hoague replied

It seems to me that you face a dilemma. On one hand, if you dismiss your action against the Bellingham Publishing Company the same ploy will be used in all three remaining libel actions [since instigated by Pauling]. Furthermore, this successful defense to this libel action might lay you open to a rash of defamation, since the defamers would know that they had a defense to any suit brought by you. Also, your dropping of this action, and I assume of the other three actions, would be used by certain columnists to indicate your admission of the truth of the accusations.

Pauling decided to disclose the names of his fellow petitioners, in spite of his desire to protect them from potential federal investigation. The list totaled about 650 names, including approximately 450 Americans.

petition-submitters

Page 1 of Pauling’s list of those who helped to circulate the bomb test petition.


In January 1962, before the case came to trial, Pauling offered the Bellingham Publishing Company a settlement: $75,000 in damages plus a retraction. After negotiating for four months, the parties agreed to a penalty of $16,000 plus a retraction. The settlement was likely close to what Pauling would have received through the full prosecution of a successful suit. The outcome also allowed him to spend less in legal fees, and was hoped to deter other news sources from libelous actions of a similar nature.

The Bellingham Herald published its retraction in May 1962, writing

In late November and early December, 1960…this paper published in its Letters to the Editor column five letters in which the writers attacked Dr. Pauling. These letters contained untrue statements which, if believed, would have reflected on Dr. Pauling’s integrity and loyalty to the United States of America. These defamatory letters were published in error in reliance upon the writers, without investigation by the paper. The Herald takes this opportunity to state publicly that it regrets that it published these statements reflecting on the integrity and loyalty of Dr. Pauling.

Three years later, in April 1965, Francis Hoague, Pauling’s Bellingham case lawyer, wrote a letter to him noting the impact that the suit had made in the community. In his observation

Up until the time when you sued the Bellingham Herald, the John Birch Society had a firm grip on city and school affairs in Bellingham and virtually no one dared to challenge them…Your suit was the turning point in this matter, and since then the John Birch Society has had relatively little influence and can be quickly and effectively challenged when necessary. Even the Bellingham Herald has shown a change of heart in liberal matters…so your efforts in that respect were not in vain.

Thirteen years after that, Pauling engaged in a conversation that makes for a compelling coda to the Bellingham story.  In a note to self dated February 27, 1978, he wrote

Mrs. Helen Mazur talked to me today. Her husband is Professor of Demography in Western Washington University, Bellingham….

She and her husband arrived at Bellingham just at the time that I came to give the Commencement lecture.  We learned when we arrived there that some derogatory material had appeared in the Bellingham Herald. I sued, and the case was settled out of court with payment of $15,000 [sic] to me.

Mrs. Mazur said that when she arrived in Bellingham just at that time she met the president of the local bank. For some reason that she does not understand he began talking to her about me, and said that he had gone to the editor of the newspaper to suggest that something be done. She says that he said that he and the editor had written a letter attacking me, which was then published in the Bellingham Herald. It was this letter, with a false name and address, that was the basis of my suit. She also said that the newspaper borrowed the $15,000 from the banker’s bank in order to make the payment to me. I had not known that the newspaper editor and the banker had conspired to write this letter.

 

Pauling and Pritikin Duke It Out Over Vitamin C

Interview Letter

Letter to Pauling from Steve Hewitt, August 1979.

Dear Dr. Pauling. Several weeks ago, the Oregonian published an interview with Nathan Pritikin. In it, Mr. Pritikin referred to two studies purporting to show adverse effects from taking vitamin C…. 

In this letter from August 1979, a concerned follower of the nutrition advice given in Linus Pauling’s then recently published book, Vitamin C, the Common Cold, and the Flu­­, confesses that, while he is following the book’s advice and is megadosing on more than a gram of vitamin C supplements every day, he is concerned about adverse effects that might arise from the practice. What, he asks, does Dr. Pauling know of a collection of studies referenced by a Dr. Pritikin and reported on in the Oregonian? Has Dr. Pauling changed his mind about vitamin C?

Pauling replies to the man with his usual clarity:

…You ask about several statements made by Mr. Pritikin. I may say that these statements are just wrong. The reason probably is that Mr. Pritikin is ignorant about vitamins.


Nathan Pritikin

Nathan Pritikin

Nathan Pritikin was a dietician who, in the 1970s, found himself in competition with Linus Pauling for the health of America.  An inventor involved in various scientific fields including chemistry, Pritikin was 40 years old when, in 1955, he was diagnosed with cardiac disease. Though a slender and fit-looking man, Pritikin’s cholesterol and blood pressure were through the roof. His doctors prescribed a series of medications and told him to rest up so as not to strain his heart.

Rather than following this advice, Pritikin began to read. Studying cultures both past and present from around the world, he concluded that heart disease (along with a variety of other degenerative diseases prevalent in the U.S.) could be fought, so long as one was armed with a proper diet and exercise program. Pritikin’s concept of a proper diet was one still followed by many today: low fat, low cholesterol, low sugar, plenty of complex carbohydrates and all the leafy greens and fresh fruit you could eat. The exercise regimen is also familiar: a moderate plan of preferably at least 30 minutes of aerobic activity per day.

For Pritikin, the diet and exercise worked. Within months his cholesterol was lower and he felt better; within a few years, his cardiac disease was a thing of the past. Equipped with the drive and instincts of a veteran inventor, Pritikin next did what came naturally – he invented a new diet and exercise plan for America and he took it to market. Starting with his “Pritikin Longevity Centers,” meant for those who suffered from degenerative diseases, and later moving to the written word, Pritikin became one of the health gurus of the 1970s and 80s, establishing himself alongside such names as Robert Atkins and Herman Tarnower, creators of the Atkins Diet and the Scarsdale Diet, respectively.

This was a space also occupied, of course, by Dr. Linus Pauling.


Pauling note to self, June 22, 1978.

Pauling note to self, June 22, 1978.

Pauling had noticed Pritikin well before he received the letter detailing the Oregonian interview. In a letter from 1977 to Dr. Miles Robinson, a mutual friend of both Pauling and Pritikin, Pauling noted his awareness of Pritikin, his only criticism of the man and his health advice being that Pritikin “neglects his vitamins.” This is about as kind as Pauling would ever treat Pritikin in his correspondence.

The following year, it became apparent to Pauling that Pritikin was not only neglecting supplemental vitamins, but had begun to speak out against them, in particular vitamin C. During a lecture given in early 1978, Pritikin implied that high doses of vitamin C could inhibit certain actions of the body’s immune system, potentially making a person more ill. After composing a memo to himself on the subject, Pauling wrote to Pritikin, telling him that several people had been made upset by his attack on supplementary vitamin C and had written to Pauling about the lecture. Pauling had just completed a paper claiming the exact opposite, complete with 386 references, and he pointed out in no uncertain terms that Pritikin was obviously incorrect in his statements.

In his reply to Pauling’s letter, Pritikin did not bow to the pressure. Rather, he went on the offensive, accusing Pauling of promoting a diet high in fat and cholesterol, ignoring any connections that these habits might have to the development of atherosclerosis. “The public,” he said in his letter, “is led to believe that this type of diet is perfectly acceptable as long as high doses of vitamin C are ingested.”

In the letter, Pritikin also included a statement and a quote that he would repeat over and over in his books, interviews, lectures and letters.  First, that humans had no need of supplements so long as they ate a diet that included vegetables and fruit. And second, according to D.L. Cooper, a doctor cited as serving on the 1972 Olympics medical board, “Americans excrete the most expensive urine in the world because it is loaded with so many vitamins,” a result of all the supplements that they ingest. Pauling answered the attack, naturally, writing that Pritikin’s referenced studies were wrong, and that the quote about excreted vitamins, specifically vitamin C, was also fictitious.

Letter from Pauling to Pritikin, August 1, 1978.

Letter from Pauling to Pritikin, August 1, 1978.


From his correspondence, we can ascertain that Pauling’s next interaction with Pritikin concerned the interview mentioned above in Northwest magazine, a Sunday insert in Portland’s Oregonian newspaper. In the interview, Pritikin was extremely derisive in his comments on vitamin C, even more so than at the lecture from the year prior. A few highlights:

Well, it’s completely wrong to take [vitamins]…For example, the most vitamin C you can hold in your body is about 20 or 25 milligrams a day. Anything over that just goes out through your urine….

If a woman is pregnant and is ready to deliver a child and she is on high vitamin C, both the mother and the child are set up to destroy vitamin C because the body can’t stand it. Now the child is born, but is not taking any new vitamin C, but the mechanism for destroying it continues for probably 10 to 15 days after you stop taking it, so on the fourth day the child goes into scurvy because its body is destroying vitamin C, but no new vitamins are coming in. Many cases are reported like that.

And, the most inflammatory, at least in the eyes of Pauling:

The bacteria count rises 100 times higher when you are on high vitamin C doses.

Thus, the more vitamin C you take, “the longer you’re going to be sick.” Reminded by the interviewer that this view was in direct opposition to Pauling’s stance, Pritikin retorted, “Well, he can make a statement, but this is what the study shows.”

Excerpt from Pritikin's interview in Northwest magazine.

Excerpt from Pritikin’s interview in Northwest magazine, 1979.

Though Pritikin called Pauling out by name in the interview, Pauling didn’t reply to the salvo, at least not directly. In addition to calling Pritikin ignorant of vitamins in his reply to his follower, he ended his letter with, “I think it is quite wrong for Mr. Pritikin to talk about vitamins when he knows so little about the matter.” He also sent a copy of his response to Nathan Pritikin.

More exchanges occurred from there, including an one in which Pritikin, as reported to Pauling by a correspondent, quoted Art Robinson – who was suing the Linus Pauling Institute of Science and Medicine at the time – in saying that Pauling was sitting on evidence that vitamin C had the potential to cause and aggravate cancer. To that concerned reader, Pauling sent a copy of a letter that he had written to the editor of The Stanford Daily that listed all his reasons why Art Robinson was wrong.

Pritikin’s final attack on Pauling’s position came during a radio interview conducted on KGO-San Francisco’s Owen Spann talk show in October 1983. Pritikin appeared on the show to promote his newest book, The Pritikin Promise: 28 Days to a Longer, Healthier Life, and to clarify some of the diet advice presented within.

After asking his guest a few questions about the recent history of American heart disease, Spann launched into a discussion on vitamin C. And Pritikin, once again, turned to a study, saying “[Stanford University] got so sick of hearing Dr. Pauling say that vitamin C cleans out your arteries that they decided to see if it even does.” From there he described the study, stating that Stanford found that vitamin C raised LDL (bad cholesterol), while lowering HDL (good cholesterol). He finished with this bold statement: “If you want heart disease, take vitamin C.”

Upon hearing a recording of the interview, Pauling went in search of the Stanford study. Pauling’s notes documenting his search suggest that Pritikin was lying.

I telephoned Dr. Donald C. Harrison, professor of medicine and head of the cardiology department at Stanford. He says that he knows nothing about the study Mr. Pritiken [sic] said was made at Stanford, and so far as he knows Stanford has made no study of vitamin C in relation to heart disease.

Pauling note to self, October 31, 1983.

Pauling note to self, October 31, 1983.

The disagreement between Pauling and Pritikin ended with the Spann interview. Though no longer suffering from cardiac disease, Nathan Pritkin had battled leukemia for most of the 1980s. In February 1985, he took his own life. He was 70 years old.

A Theory of the Color of Dyes

Image credit: Kanwal Jahan.

Image credit: Kanwal Jahan.

Colors convey ideas and emotions in such fundamental ways that being able to capture and use them has been an important component of both cultural and scientific development. The colors of the natural world have fascinated people throughout human history and unending attempts have been made to manipulate and apply color to the items that we use on a daily basis.

Linus Pauling was not immune to humankind’s curiosity for color and as a chemist he was intrigued by dye molecules. Seventy five years ago, in 1939, he attempted to deepen the scientific understanding of how these molecules reflect color.

By the late 1930s, chemists had become comfortable with the concept of electronic resonance – the ability of electrons in a molecule to change orbitals – and were using it to describe a molecule’s capacity to absorb and emit radiation in the reflection of color. Atoms and molecules possess electromagnetic radiation due to the charge of their electrons, and as light hits an atom or a molecule its radiation determines which wavelengths of light are absorbed and which are emitted. When a molecule resonates, the movement of electrons causes a shift in the charges within the molecule which affects its radiation and the distribution of its atoms. All of these processes impact the molecule’s absorption-emission spectra.

By the time that Linus Pauling began working with dyes he had already contributed greatly to the theory of resonance. In 1928, while looking at a series of proposed forms for resonating molecules, he realized that the likelihood that these molecules would resonate directly from one form to another was very low. While many of the resonance forms that had been proposed explained the chemical behavior of molecules, Pauling felt that something was missing in the contemporary understanding of resonance. In his 1928 paper, “The shared-electron chemical bond,” he proposed that the shifts in charge observed in larger molecules required intermediate resonance forms. Pauling then described how these shifts in charge occured from one atom to the next, in the process altering the molecule’s geometry. This idea ran contrary to the notion that electrons shifted directly from one side of the molecule to its opposite.

In 1939 Pauling applied these ideas to the molecules that make up dyes. Dye molecules are often large organic compounds highly affected by resonance. This fact was known to chemists at the time, yet Pauling disagreed with accepted ideas on how these compounds resonate and reflect color. To Pauling, it seemed unlikely that molecules the size and structure of, for example, benzaurin and indigo would resonate in such direct ways as was being proposed by his colleagues.

Although the dramatic changes in charge and structure that had been proposed did account for the colors reflected by dye molecules, Pauling had developed a different understanding of how they came about. Instead of electrons resonating and causing a shift in charge directly from one side of the molecule to the other, Pauling suggested that the shift occurred from atom to atom, giving rise to intermediate forms. Pauling believed that it was necessary to take into account all possible resonance forms in order to fully understand a dye’s emission spectrum.

Some of the multiple resonance forms proposed by Pauling for Döbner's violet. 1939.

Some of the multiple resonance forms proposed by Pauling for Döbner’s violet. 1939.

Pauling’s thinking was published in a 1939 article, “A theory of the color of dyes,” which appeared in the Proceedings of the National Academy of Sciences. The article verifies the notion that color depends on the frequencies of radiation generated by the electrons in a molecule. But it also suggests that in order to understand their molecular structure and explain the colors that these molecules reflect, it is necessary to consider all possible distributions of a molecule’s charges, a combination of which would more accurately describe the observed reflection of color. Scientists now agree that understanding absorption-emission spectra is key in describing molecules because they offer valuable information about a molecule’s components and charges; Pauling’s dye work was a contribution to the development of this understanding.

At the time that Pauling’s theory of dyes paper was published, there were chemists across the country simultaneously trying to understand the color phenomenon. Dr. A. Burawoy’s 1940 article “Light Absorption, Resonance, and Isomerism” (Journal of the Society of Chemical Industry) used Pauling’s 1928 shared electron bond paper in developing his own study of dyes. Not surprisingly, Pauling and Burawoy reached similar conclusions about color.

Crellin Pauling and a friend peer out from a railroad car in an early color image from the Pauling Papers. Image digitized from a Kodachrome slide original.

Crellin Pauling and a friend peer out from a railroad car in an early color image from the Pauling Papers. Image digitized from a Kodachrome slide original.

Other chemists, including L.G.S. Brooker, would contribute to Pauling’s theory of dyes by questioning and expanding upon his work. Brooker was a chemist working for the Eastman Kodak Company in Rochester, New York. The company was naturally interested in producing higher-quality photographic film and, as such, was keen to investigate and understand the chemistry of dyes. Brooker and Pauling exchanged ideas as they studied dyes, and correspondence from December 1937 suggests that the two met in Rochester the following month to discuss their results. When Pauling’s theory of color was published in September 1939, Brooker wrote to issue a disagreement with Pauling’s treatment of carbon molecules. Specifically, Brooker believed that Pauling was overlooking the possible effects of carbon on a molecule’s behavior, though he otherwise agreed with Pauling’s conclusions on radiation and charge migration.

Observations like Brooker’s encouraged Pauling to continue his study of dyes by testing his theory on different molecules, including synthetic dyes like cyanine, which he investigated in 1940. The application of Pauling’s findings on carotenoids, one of the pigments found in tomatoes, was further expanded in a 1941 article published by Laszlo Zechmeister, Pauling and two other Caltech colleagues and titled, “Prolycopene, a naturally occurring stereoisomer of lycopene.” (Proceedings of the National Academy of Science)  Two years later, Zechmeister, Pauling and three others authored “Spectral characteristics and configuration of some stereoisomeric carotenoids including prolycopene and pro-gamma-carotene.” (Journal of the American Chemical Society)  Both publications explored the role of molecular structure in determining the emission spectra of naturally occurring pigments.

The contemporary understanding of how dye molecules reflect color has changed little since Pauling’s 1939 findings. His work, and that of many others scientists, confirms that something as simple as the color of a tomato is the result of a continuing cycle of complex interactions between atoms and their electrons.

Mary Mitchell, Resident Scholar

mary-mitchell

Mary Mitchell

Mary Mitchell, a doctoral candidate in the history and sociology of science at the University of Pennsylvania, recently completed her term as Resident Scholar in the OSU Libraries Special Collections & Archives Center.  Mitchell is the first of the 2014-15 class of Resident Scholars to complete her work here in Corvallis.

Mitchell’s research subject was the Fallout Suits, a topic that has been examined by two previous resident scholars, Toshihiro Higuchi (2009) and Linda Richards (2011).  However, where Higuchi examined this chapter of Pauling’s activism through the lense of environmental impact and Richards viewed the case as an instance of early human rights intervention, Mitchell, who has a background in law, is interested in the broader socio-legal milieu that surrounded the Paulings and their allies as they pursued their objectives.

The Fallout Suits can trace their origin to March 1st, 1954, when the United States tested the most powerful bomb ever to be exploded. The site for test Castle Bravo was Bikini Atoll in the Marshall Islands, then a U.S. territory. The blast came from a hydrogen bomb and was seen over 100 miles away. Radioactive debris from the test exploded high into the atmosphere and spread across the Pacific Ocean, carried by wind and water and causing damage to fisheries and ecosystems across the region.

"Castle Bravo," the first hydrogen bomb test, March 1, 1954. (U. S. Dept. of Energy photograph)

“Castle Bravo,” the first hydrogen bomb test, March 1, 1954. (U. S. Dept. of Energy photograph)

The strength and destructive power of the blast far exceeded the expectations of the scientists who developed the bomb and quickly became an issue of international attention, mainly due to concerns over the spread of radioactive debris – fallout – which resulted from the test. Activists who saw radioactive fallout as a threat to the health and well-being of the public began to protest the continuation of these tests, leading at one point to a series of lawsuits filed against the governments of the United States, the Soviet Union and Great Britain.

This bundle of litigation, which sought to obtain judicial restraint to end nuclear weapons tests, quickly became known as the Fallout Suits.  The American plaintiffs were Linus Pauling, Karl Paul Link, Leslie C. Dunn, Norman Thomas, Stephanie May and William Bross Lloyd Jr.  This group was joined by several additional plaintiffs from Japan and Great Britain.

Mitchell’s research indicates that, during this chapter of the Cold War, Pauling was able to voice his opinions in a more successful way than was the case for lower-profile scientists of the time. While Pauling was indeed tracked by the FBI, the Senate Internal Security Subcommittee and other U.S. government entities hellbent on sussing out communist activities, Mitchell suggests that Pauling’s celebrity was both “his sword and shield” throughout the struggle. Pauling’s receipt of the Nobel Prize for chemistry and the fame that came with it protected him, at least to a degree, from being quieted as easily as was the case for other citizens at the time. Yet Pauling could not argue alone; in his fight against government policy he would need the support of other scientists to provide not only their opinion, but also their research, showing that nuclear testing is a threat to the public.

According to Mitchell, this strategy in Pauling’s fight against nuclear testing stemmed from his belief that democracy was only complete when citizens are given complete information in order to participate in the politics of their nation. As a scientist, Pauling knew that while nuclear testing could strengthen the military power of the United States, there were much broader consequences to this practice. He believed that the public should be informed about the dangers of nuclear testing and that the citizens of the United States should have a voice in determining whether or not these tests should continue. Pauling was especially firm in his belief that, as citizens, scientists should participate in public affairs by providing the public with information that would help individuals to make informed decisions when exercising their democratic rights.

Fallout Suits brochure, 1958.

Fallout Suits brochure, 1958.

Though they gained the support of other scientists, the plaintiffs behind the Fallout Suits lost without even getting a trial; the courts took a stance on issues of justiciability (limitations on issues over which a court can exercise its authority) and standing (appropriateness of a party initiating a legal action) in dismissing the lawsuits. Additional Marshallese lawsuits were dismissed on the grounds that the plaintiffs were not U.S. nationals, even though the Marshall Islands were a territory of the United States.

Mitchell concluded her Resident Scholar talk by noting that, despite their ineffectiveness in compelling immediate government action to reduce nuclear testing, the Fallout Suits led to “new forms of participatory democracy, stretching trans-nationally across the Pacific Ocean,” forms of democracy which “had risen from the ashes of America’s testing program.”  Moving forward, Mitchell will continue to dig into the research that she conducted at OSU as she develops her dissertation on legal challenges to atmospheric testing.

For more on the Resident Scholar Program, now in its seventh year, please see the program homepage and our continuing series of posts on this blog.

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The Discovery of Human Plastin at the Pauling Institute

Milestones in Plastin Research

[Guest post written by John Leavitt, Ph.D., Nerac, Inc., Tolland, CT.]

In 1985 my lab at the Linus Pauling Institute of Science and Medicine (LPISM) in Palo Alto, California started to work on an abundant protein of white blood cells (lymphocytes, macrophages, etc.) that mysteriously appeared in human tumor-derived cells of solid tissues (carcinomas, fibrosarcomas, melanomas, etc). I had noticed this phenomenon a few years earlier while at the National Institutes of Health. I also noticed that this protein appeared in oncogenic virus-transformed (SV40 virus) human fibroblasts, but the protein was not expressed in the normal fibrolasts.

I was intrigued by the fact that a major protein of circulating blood cells would be induced during solid tumor cell development because it is well known that solid tumor cells become more anchorage-independent and can circulate like white blood cells to metastasize to other organs. My colleague, David Goldstein, took the lead in examining the expression of this mysterious protein in different cell types of fractionated white blood cells. At the time this protein was assigned only a number (p219/p220) corresponding to its position in two-dimensional protein profiles. We found that this protein was abundantly expressed in all normal white blood cell types that we examined but it was not expressed in normal cells of solid tissues (Goldstein et al, 1985).

When David’s paper was submitted to Cancer Research, the reviews came back positive and the paper was accepted for publication, but one reviewer asked that we give the protein a name. I was thrilled by the thought of naming a protein and its gene which would immortalize our work, so I took on the serious task of coming up with a name that had lasting meaning. My theory was that this cancer marker contributed in some then-unknown way to the plasticity of the cytoplasm in solid tumor cells because of its normal presence in circulating white blood cells. Also, I had seen the great movie, The Graduate, with Dustin Hoffman and recalled that amusing scene depicted in the picture included below. So I named the protein “plastin” – the greatest new thing since sliced bread. :)

The Graduate

That same year, I met Steve Kent from Caltech at a meeting in Heidelberg, Germany. After hearing my talk, Steve suggested that we collaborate. He mentioned that a postdoctoral fellow in Leroy Hood’s lab, Dr. Ruedi Aebersold, was trying to develop a more sensitive protein sequencing method for purposes of determining snippets of amino acid sequences from small amounts of unknown proteins eluted from two-dimensional gels (protein profiles) like the gels that we used to characterize plastin in David’s paper. If we could get an accurate partial sequence of plastin, we could devise a nucleic acid probe based on the genetic code that could be used to clone a plastin “copy DNA” from a cDNA library. If the plastin cDNA was cloned, we could then define the protein and perhaps its function by determining the nucleic acid coding sequence in the clone.

Madhu Varma.

Madhu Varma.

I gave Dr. Madhu Varma at LPISM the arduous task of isolating the plastin polypeptide “spot” for sequencing. Madhu cut out the stained spot from 140 two-dimensional gels, in effect purifying enough protein for sequencing by Ruedi at Caltech. Madhu succeeded and Ruedi produced eight short peptide sequences that could be used to develop short nucleic acid probes that would hybridize to the plastin cDNA clone isolated from a tumorigenic human fibroblast cDNA library.

Ching Lin.

Ching Lin.

Dr. Ching Lin at LPISM took one of the nucleic acid probes and immediately attempted to screen a tumorigenic fibroblast cDNA library. If we identified any clones that bound this probe, then we would perform a quick test to determine that we had cloned the plastin coding sequence. But science is full of surprises and we found that the first clone he isolated detected a gene product that was not in lymphocytes but only in normal human fibroblasts – in other words, it failed the test. This is where Ching’s brilliance took over. He was convinced that this first clone he had isolated was indeed a plastin coding sequence so he used this clonal DNA as a new probe against the tumorigenic fibroblast cDNA library. He isolated a new clone that passed the test and detected a gene that was expressed in lymphocytes and tumorigenic fibroblasts but not in normal human fibroblasts.

We performed other experiments that proved that we had cloned two different isoforms of plastin: L-plastin, expressed in lymphocytes and solid tumor-derived cells, and T-plastin that was expressed in normal solid tissues and co-expressed with L-plastin in tumor cells from solid tissues (Lin et al, 1988; Lin et al, 1990). Ultimately this work led to the complete characterization of the human plastin multigene family and verification that both isoforms were aberrantly expressed in various types of human tumors.

The figure at the top of this post maps the progression of discovery that followed our research, which began at the Pauling Institute in 1985. Our publications are shown in red in the graph and research published by other labs is shown in the blue bars.

Here are several plastin milestones discovered by other researchers:

  • T-plastin is abundantly induced in Sezary lymphomas, a lethal T-lymphocyte cancer (Su et al, 2003);
  • L-plastin induction in solid tumors contributes to invasive cancer growth and metastasis (Klemke et al, 2007);
  • Mutations in T-plastin play a role in the genetic disease Spinal Muscular Atrophy (Oprea et al, 2008); and
  • Most recently mutations in both L- and T-plastin promote re-growth of colon carcinomas following surgical resection of these tumors and chemotherapy (Ning et al, 2014).

These developments are more or less typical of the way science works. Progress in understanding complex phenomena like human cancer is the work of many scientists that builds on the observations of other scientists. This is just one example of the productive contributions in biomedical research that came about through early discovery research at LPISM in the 1980s.

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