General Chemistry: Reactions to the First Edition

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[An examination of General Chemistry, published by Linus Pauling seventy years ago. This is part 3 of 7.]

The first edition of Linus Pauling’s General Chemistry textbook was published by W.H. Freeman and Co. in August 1947, and almost immediately the comment cards poured in. The majority of the book’s readers praised Pauling’s refreshingly modern approach to the principles of chemistry. They considered his focus on modern chemical principles, with only brief and necessary digressions into historical background, a welcome innovation in textbook design.

Many also were also impressed by Pauling’s clear and direct approach to his subject matter, with one reviewer commenting that

[Pauling’s book] is written in a way which should appeal to the imaginations of those who happen to possess them, which is perhaps as important as anything that can be done.

Reviewers were likewise nearly unanimous in their enthusiasm for Roger Hayward’s skillful illustrations, pointing out the degree to which his depictions were a truly extraordinary asset, especially for concepts known to be sources of difficulty for students.


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That is not to suggest, however, that the first edition was uniformly accepted as flawless. Indeed, over half of Pauling’s reviewers declared the book to be too advanced for it’s announced audience: first year students. Moreover, many also noted that the book actually discouraged all but their most determined introductory pupils from moving forward because of the difficulties that they encountered with some of the fundamental principles that Pauling laid out.

Many of the professors who found the text to be too challenging believed that Pauling had mistakenly used Caltech as the standard by which to measure all incoming college freshman. But while their opinion that Pauling had miscalculated in this regard was fairly consistent, the collective did not provide a consensus on who might be an appropriate target audience for the book; reviewers’ suggestions ranged from advanced freshmen to pre-professional students.

In fact, Pauling did have Caltech freshmen in mind when he wrote the book, and very intentionally so. When he embarked upon the project, he made clear that his primary ambition was to develop a text that would prove useful to students who shared his own early enthusiasm for chemistry and who were prepared to devote their academic careers – and, ideally, their professional careers – to the study of chemistry. In the eyes of many though, this approach was not appropriate to other institutions of higher learning and the question of ideal audience remained a point of contention for the entire life of the book.


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Several professors who argued in support of the text tended to feel that its advanced nature was actually the best possible asset that could be provided to specific cohorts of students: in particular, students blessed with sufficient high school experience and/or interest, as well as students who made up for their lack of experience with enthusiasm and perseverance. A few years after Pauling first published his book, a California professor commented that, in his higher-level class, students using General Chemistry applied essential material more effectively and achieved higher rates of success in upper-division chemistry courses overall.

Other positive reviewers focused more intently on Pauling’s technique and powers of description. Scripps professor Norris Rakestraw called Pauling’s review of molecular structure “one of the best approaches to an understanding of general chemistry” and also agreed with others who claimed that the book had the potential to propel students to a more rigorous level. If perhaps not ideally suited for freshmen, Rakestraw believed that General Chemistry was certainly perfect for a refresher course.

Several others followed suit. A.L. Rathmer suggested that Pauling’s “unorthodox and unconventional” treatment was valuable to teachers and other researchers in the field. A reviewer from Northwestern University phrased a similar sentiment in a decidedly different way:

Any instructor who fails to read this text should be fired – and any instructor who tries to use it with freshman should also be fired.

A smaller group of professors offering mixed reviews pointed out that Pauling’s own research interests – particularly his biochemical interests – seemed to dominate the text. A few went so far as to accuse Pauling of using his book as a platform to advance his own scientific theories. Pauling, who was generally open to feedback, did not respond to these comments except to disclaim them in fragmented notes scribbled in the margins of letters and review cards.


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One oft-issued request that did receive a response from Pauling was that he release an answer key to the book’s exercises. He worked on this key during the summer of 1947 while he was working as a visiting professor at Oxford University, and he enlisted his son, Peter, to work through the problems alongside him, verifying answers and identifying problematic practice questions.

Reacting to a different set of complaints, Bill Freeman suggested that the publishing house also compile and release a laboratory manual that was specifically designed to accompany the text. Settling on a length of 290 pages with 80 Hayward illustrations, Freeman worked with Pauling to select Harper Frantz, a lecturer at Pasadena City College, and Lloyd Malm, a University of Utah chemistry professor, as co-authors. Frantz and Malm in turn developed experiments that were based on and that further amplified the principles described in General Chemistry.


Pauling was not only unconventional in his approach to subject matter, but also in how he used his terminology. Two prominent examples of this tendency were his representation of Avogadro’s number and his use of the term “molality” in the place of “molarity.”

Avogadro’s number defines the units in one mole of a solution and is typically set at approximately 6.022 x 1023. Pauling, however, chose to write the number as 0.6023 x 1024. Even when several colleagues urged him to stick to generally accepted convention, Pauling insisted on representing the number as 0.6023 x 1024 and continued to do so throughout all three editions of General Chemistry. In defending his point of view, Pauling offered this explanation in a footnote:

There is great convenience in learning Avogadro’s number as 0.6023 x 1024. An important use of this number involves the conversion of the volume of a gram-atom of an element into the volume per atom. The first volume is expressed in cm3, and the second in Å3. The relation between cm3 and Å3 involves the factor of 1024 : 1 cm3 = 1024 Å3. Accordingly, in case that Avogadro’s number has been taken as 0.6023 x 1024, there is no trouble whatever in deciding on the position of the decimal point.

In other words, by simplifying Avogadro’s number in an unorthodox way, Pauling was trying to make the concept easier to learn for students.

He defended his choice to use “molality” in a similar fashion, referencing A.A. Noyes, Ernest Swift, and W.C. Bray as among those who used “molality” to refer to moles per liter of solution. Pauling incorrectly believed that the term would eventually prevail within the discipline and therefore felt that students would be well-advised to familiarize themselves with it. Eventually he conceded that his was not destined to be the conventional wisdom and he changed “molal” to “molar” in the second edition.

Indeed, throughout the lifespan of General Chemistry, Pauling trusted that students using the book would come equipped with a firm grasp on the language of chemistry. He did, however, agree to provide more definitions in the second edition, particularly for less common or more advanced terms.


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Ava Helen and Linus Pauling, 1948.

While there was widespread disagreement about the appropriateness of using Pauling’s book in freshman classes, very few reviewers disputed General Chemistry‘s strength in content. One colleague, J.S. Coles, who later went on to author a textbook of his own, published a review of Pauling’s first edition and followed it up with a letter in which he emphasized that

Even if every suggestion or criticism [contained within the review] were completely ignored, I would continue to believe [General Chemistry] far ahead of any other text in the field and would continue to use it in any of my courses wherein I thought it to be appropriate.

Many professors who did not adopt the text for their courses admitted to keeping a few copies on hand for themselves and, on occasion, for their advanced students. More still reconsidered their initial rejection of the book when the Frantz-Malm laboratory manual came out in 1949. Of the overall response to General Chemistry, Bill Freeman wrote, “Oh we will slip from grace now and then – I hope it will be because we are trying to improve on the conventional.”

What is beyond doubt is that General Chemistry was wildly successful, even if it didn’t always reach its intended audience, and the royalties that Pauling received provided him with a new level of financial comfort. While most of the windfall was used to support Pauling’s ambitious travel schedule, he did choose to invest in at least one comfort item: an outdoor pool at his Pasadena home.

Affectionately dubbed by his children as “the pool that General Chemistry built,” the space quickly became a gathering spot for some of Pauling’s luckier graduate students, and evolved from there into a location where students could engage Pauling in lively conversations and solicit advice. Not unlike Pauling’s book, these conversations, on any number of occasions, led to insights that shifted the entire course of a student’s professional trajectory.

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An Auspicious Friendship

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[An examination of General Chemistry, published by Linus Pauling seventy years ago. This is part 2 of 7.]

William Hazen “Bill” Freeman established the publishing firm of W.H. Freeman and Company in 1946. On breaking with his previous employer MacMillan Publishers, Freeman said simply, “We made so bold a move because we found that every factor contributing to the success of such a venture was at hand, waiting to be put to work.” There is little doubt that Freeman was thinking of Linus Pauling when he made this statement, but his confidence was also born of extensive experience in the publishing world, working especially with college textbooks.

Freeman brought all his resources and skills to bear on Pauling’s General Chemistry manuscript. He began by circulating early drafts of the text to curate specific feedback in cases where he himself was not equipped to offer it. He also promoted the finished text tirelessly and, through the process, worked without complaint around Pauling’s complicated lecture and travel schedule. Put simply, Freeman knew that he had a singular resource in hand with Linus Pauling, and he did his best to do right by this relationship, both out of respect for Pauling and out of interest in building his business.


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Illustration prepared by Roger Hayward for use in General Chemistry, 1947.

Without question, another individual who contributed greatly to the success of General Chemistry – and to W.H. Freeman and Company – was Roger Hayward, who joined the duo early on as an illustrator at Pauling’s insistence. Hayward moved from the East Coast to Pasadena in 1929, upon which time he became a member of the Caltech One-Hundred-to-One Shot Club, which was comprised of individuals interested in astronomy. Through this connection, Hayward gradually came to be involved with several projects involving Caltech faculty and ultimately met Pauling in the 1930s.

Hayward was an architect by training and Pauling so respected his skill as a draftsman and an artist that he insisted that he was the only one up to the task of creating illustrations for General Chemistry. Pauling was no doubt attracted to Hayward’s unique approach to scientific illustration, wherein he conducted in-depth and detailed research on the scientific principles underlying his topic before ever setting pencil to paper. Freeman also recognized Hayward’s unrivaled skill, and enlisted him on a number of other projects beyond Pauling’s text. By the end of their partnership, Pauling considered Hayward to be not only a collaborator and a friend, but a scientist as well.

As the General Chemistry text was being developed, Pauling evinced such faith in Hayward’s abilities that he offered to transfer .05% of his royalty rate to the illustrator, a payment that would be made in addition to the fee that Freeman and Co. had contracted for the illustrations themselves. Bill Freeman agreed to this arrangement and generously matched Pauling’s offer such that Hayward ultimately received royalties at the rate of 1% for every copy sold – a rate nearly as high as Pauling’s 1.5% royalty agreement.

While seemingly generous, this understanding later proved to be fraught with complications, and Hayward often complained that Freeman and Co. did not adequately compensate him for the amount and quality of work that he contributed. Pauling and Freeman, growing exasperated with this behavior, privately agreed that Hayward was a key contributer but also a “bit of a prima donna.”

Nonetheless, Freeman deeply respected Hayward as a serious artist and clearly understood the value that he brought to the company. As a result, he strove to adjust financial arrangements so that they would benefit all parties involved. For a brief period in the early 1950s, Freeman even brought Hayward on under contract as a staffmember at Freeman and Co. Although the arrangement ended before Hayward’s ten-year deal had expired, the two men deeply appreciated the friendship they shared. Indeed, even in the midst of sensitive and difficult financial negotiations, their letters often ended with mutual expressions of hope that they would see one other soon.


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Under Freeman’s stewardship, Pauling’s manuscript underwent a number of important changes. Initially organized into thirteen chapters, the text was ultimately divided into thirty-three chapters by the time of its publication. In so doing, Freeman and Pauling agreed to remove an initial chapter on valence, choosing instead to disburse the subject matter into a series of subsections located throughout the book.

Likewise, in the manuscript version, Pauling had included a small introductory paragraph on the broader subject of chemistry before diving into his material. In the published book, Pauling instead dedicated his entire first chapter to the importance of studying chemistry as well as the mission and philosophy of the textbook that he had written to help aid in this endeavor. This change allowed Pauling to provide guidance to students on how they might use the book itself, a particularly important addition given that he was breaking from traditional pedagogical styles.

Freeman and Pauling also decided to move chapters on chemical reactions, the properties of gases, and thermochemistry to the end of the book, judging these topics to be sufficiently advanced that a strong foundation on elementary topics should be established first.

Most of the changes that Pauling and Freeman made reflected a desire to create more space to explore topics and to build logical connections between sections and chapters. In the chapters that Pauling eventually added, he covered specific elements like sulfur and nitrogen, as well as compounds including water and several metals. Other changes in chapter order enabled deeper introductions to substances and solutions prior to walking readers through investigations of matter, properties, and variations.


As late as 1947, mere months before Freeman and Co. released the book, Pauling was still calling his text Principles of Chemistry. Freeman suggested that the title be changed to A General Chemistry, because he felt that it conveyed a sense of modesty.

Once Pauling had dropped the indefinite article in favor of a more authoritative title, General Chemistry, Freeman offered him three possible subtitles from which to choose: “An Introduction to Modern Theory and Descriptive Chemistry,” “A Statement of Modern Theory and Descriptive Chemistry,” or “An Introductory Statement of Modern Theory and Descriptive Chemistry.” Pauling eventually synthesized the three into “An Introduction to Descriptive Chemistry and Modern Chemical Theory.”

This subtitle reflected Pauling’s goal for the book itself: in his text, he sought to present descriptive chemistry and theoretical chemistry alongside one another to illustrate their equal significance and impact. His first chapter made clear that he felt practical work, in tandem with study and review of the facts of chemistry, were vital to a full understanding of the subject. In reflecting on this point, he noted that

A well-educated man or woman needs to have an understanding of the material world in which he lives as well as of literature and history, and he may find great pleasure in the appreciation of new knowledge as it results from scientific progress.


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Once Pauling had a completed his draft, he and Freeman fell into a rhythm, editing the manuscript collaboratively through a series of memos and letters. Pauling typically submitted one chapter at a time, to which Freeman would quickly reply with corrections and suggestions. From there, Pauling would counter by accepting, rejecting, or offering alternate suggestions. In effect, the letters acted as a written dialogue between the two; Freeman providing detailed explanations with his feedback and Pauling taking care to respond and explain his choices.

By February 1947, Freeman told Pauling that their collaboration had exceeded his initial expectations for progress, but that they still needed to keep pushing if they hoped to have a successful first year. The publisher’s goal was to sell between 13,000 to 16,000 copies of the book within its first year in circulation, but this number would only be attainable if they had shipped review copies to professors before the end of spring term.

Subsequently, the two increased the pace of their correspondence and managed to get 500 review copies out by the end of May 1947, with an official release date set for that September. The estimated price of the volume was $4.25 per copy. It would span 600 pages and include 160 of Hayward’s illustrations. Just prior to printing, Pauling wrote a preface that stated his goal for the text:

a special effort has been made in this book to present the subject of chemistry in a logical and simple matter, and to correlate descriptive chemistry with the theories of chemistry.


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Comment sheet collected by Bill Freeman, 1947.

As they neared completion, Pauling offered to assist with his own marketing by proposing that he send a table of contents and brief description of the book to former Ph.D. students from Caltech who were now teaching classes of their own. Freeman gently declined this idea, explaining to Pauling that an author did not conventionally promote his own text and asking that all marketing activities be left to the publishing house. Freeman and his assistant, Janet MacRorie, subsequently created a vigorous advertising plan, targeting chemistry professors at all major universities as well as several smaller institutions. The publishers also sent out an open later including excerpts from the book that Freeman believed best demonstrated Pauling’s distinct and straightforward writing style.

In April, Freeman and Co. sent page proofs of the first five chapters of the book to fifteen different schools, with the idea that doing so would allow them to receive and incorporate feedback in the finished product. The response was overwhelmingly positive, but did contain points of constructive criticism that provided direction for revision. Reviewers typically highlighted passages that they felt would be too complex or confusing for their own classes, drawing from their own unique experiences working with undergraduates.

Freeman collected the primary concerns expressed about the book and organized them for Pauling to review. Though some felt that the text was too challenging, Freeman remained confident that even those who were critical in the beginning would return to it if Pauling spent the next year collecting observations and announcing plans for revision at a forthcoming date.

Pauling and Freeman were both deeply invested in the project, so much so that, when it came out, Freeman told Pauling that he felt like a “first time father in the maternity ward.” Once the final version arrived back from the printers, it became clear that Freeman’s commitment to meticulous editing had paid off; Pauling remarked that he had never seen such an extensive publication that contained so few errors.

The duo soon had further reason to celebrate: by June 1948, over forty colleges had adopted or were planning to adopt General Chemistry. Meanwhile, Pauling’s royalties for the first printing of the book summed to nearly $3,700 (over $38,000 in today’s dollars) and continued to increase over the next ten years, bumping up significantly more after the release of the second edition. By the end of 1950, eighty-three colleges had adopted General Chemistry and Pauling’s royalty rate had increased from 1.5% to 3%For author and publisher both, this project was already a huge success.

General Chemistry

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[Ed Note: Today we begin a lengthy examination of Linus Pauling’s milestone textbook, General Chemistry, which was published seventy years ago. This is part 1 of 7.]

Linus Pauling’s first college textbook, General Chemistry, revolutionized science textbook publishing and changed how professors, students, and authors approached introductory texts. The first edition was published in 1947 by a fledgling independent press, W.H. Freeman and Company, that enjoyed its first taste of success as a result of Pauling’s book. And what a success it was! General Chemistry was on the market for over twenty years, was translated into more than ten languages, and was adopted at almost 200 universities in the United States alone. Over the next several weeks, we will endeavor to tell the story of how this book came to be and the significant impact that it ultimately made.


Several years before Pauling set out to write a book himself, he noted that the science texts in current use – particularly freshman and introductory texts – often failed to keep up with new and updated theories. This concerned Pauling as he firmly believed that introductory texts were an important foundation to a scientific education.

He likewise worried that authors of such texts often attempted to cram too much information into their pages and in the process lessened the student’s opportunities to gain practical experience from their education. In addition, Pauling felt that authors of the day tended to present their subjects chaotically and too often failed to distinguish guiding principles from constituent components. Even when an author did identify distinguishing principles, Pauling complained that their bias further inhibited students.

Clearly this situation could be improved upon, and in his initial notes on the topic, Pauling began to sketch out a vision for what would later come to pass, recording a variety of observations like the following:

I believe that a book would be valuable to young students which gave them concrete pictures of molecules as we now picture them. Ionic substances could well be described as containing spherical [sic] given by ‘crystal radii,’ the electrons staying mostly within.

As he surveyed the pedagogical landscape, Pauling identified a particular need for improvement in instruction on theories of atomic structure as well as ideas emerging from quantum mechanics, statistical mechanics, and thermodynamics. Accordingly, he began preparing lessons and supplementary materials on these topics for use in his own teaching. These materials, which eventually took on the form of a booklet, touched upon new theories while also providing concise explanations and discussions of the practical applications of various older theories. Pauling updated this booklet frequently, using it to supplement Joel Henry Hildebrand’s Principles of Chemistry, the textbook of choice for many introductory-level chemistry classes, including those taught at Caltech.

As time moved forward, Pauling became more serious about reformatting and publishing a version of his classroom booklet, which mostly consisted of a semi-formal collection of notes. As he developed his publication plan, Pauling drew up an outline of the subjects that would want to discuss in his text. He also jotted down thoughts on general formatting as well as broad introductory remarks on the importance, history, and daily application of chemistry. Having thrived as a lecturer for over a decade already, Pauling felt that he had far more to offer to students than a rote recitation of past discoveries, results and publications. Indeed, his ultimate ambition was to re-imagine the very foundations of chemistry education.


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Pauling eventually had his revised booklet, which he titled Elementary Chemistry: The Facts and Basics of Chemistry and their Significance in Modern Life, lithographed for the purpose of aesthetics and ease. As he later remarked to publisher Bill Freeman, he did not consider this collection, even after he had it lithographed, to be a separate draft. On the contrary, this version of what would become a major textbook was to be regarded as a snapshot of a stage in Pauling’s writing process.

Pauling didn’t formally announce his plans to publish a textbook until 1941, by which time he had generated a more organized draft of thirteen mimeographed chapters. He changed the title of his manuscript to General Chemistry: A First-year Course to Follow a Year of High School Chemistry, and by the early months of 1942 he had a group of ten publishers competing for the opportunity to publish his book.

Choosing which publishing offer to accept proved to be a difficult process for Pauling. By 1942, Pauling had emerged as a star within the world of science and several publishers recognized full-well the likely benefit of having his name associated with their company. For his part, Pauling strove to find a publisher who recognized the value of the book itself, regardless of the name attached to it.

John Wiley & Sons was the first company to approach Pauling about his manuscript but the relationship quickly soured, partly because Pauling had become extremely busy. Burdened by a great many other duties, Pauling did not appreciate Wiley’s stipulation that he wait until they had “thoroughly examined the manuscript” before allowing him to send it anywhere else. The final straw came about when Wiley expressed skepticism that Pauling would finish his text in a timely manner; annoyed, Pauling withdrew the manuscript from their consideration.

W.B. Saunders Company approached Pauling next and expressed such a genuine and deep interest in his work that Pauling began negotiating with them shortly after they had made their initial pitch. Saunders had substantial experience publishing scientific texts and, unlike Wiley & Co., believed so completely in the Pauling book’s potential to succeed that they proposed a royalty rate of 15% for each retail sale. (J.C. Stacey Inc., another company in the running at the time, learned what Saunders was proposing and advised Pauling to accept the offer, as 15% far exceeded the standard royalty rate being tendered to authors at that time.) Saunders also offered to send Pauling’s preliminary draft to a chemistry professor for initial feedback and to finance a graduate student to assist with the detail work.

Encouraged by the host of publishers clamoring to publish his work, Pauling continued to revise his manuscript. This steady rhythm was interrupted when the United States entered World War II, a point at which Pauling quickly realized that his government-funded war projects were going to require his full attention. Discouraged from writing, but recognizing the importance of what he was doing, he sent out a copy letter to all publishers interested in his manuscript. In it, he stated that the present circumstances were such that he was unlikely to make much progress on his book. When the war concluded in 1945, many of these publishers inquired again, but by then Pauling had made his decision.


 

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Cartoon tipped into Pauling’s first edition, first printing of General Chemistry, 1947.

William Freeman, a representative of the college department at MacMillan Publishers, had approached Pauling in 1941 to express MacMillan’s interest in Pauling’s manuscript. A strong contender from the beginning, MacMillan had enticed Pauling with their experience as a mainstream textbook publisher. The company’s associate editor also promised Pauling the best editing services and attention around.

In the end however, it was Bill Freeman who won Pauling over. Since Freeman worked at MacMillan’s San Francisco branch, he offered to meet with Pauling in Pasadena to discuss, in person, the means by which they might partner to navigate the publishing world and protect Pauling’s rights as an author. Pauling was concerned that Macmillan, though a major player in the textbook industry, hadn’t published many scientific volumes. Freeman replied candidly, pointing out that this was actually a good thing because it meant that Pauling wouldn’t have to compete for marketing resources within the company.

Freeman also assured Pauling that, although a high royalty might look good in the short-term, a lower royalty, such as the one that MacMillan was offering, would allow the company to market the book at a lower cost. Doing so, Freeman argued, would ensure a higher volume of sales for Pauling’s text and, consequently, a more widespread adoption. Pauling was impressed. After meeting with Freeman, he returned Saunders’ contract completely blank.

When the U.S. entered the war, Pauling sent MacMillan the same letter that he had sent to everyone else, detailing the time conflicts that he was confronting with his scientific war work and announcing that the book project was moving to the back burner. But as the war years went by, Pauling and Freeman stayed in touch, and the relationship that the two men developed during this period made all the difference.

When Freeman decided to strike out on his own as an independent textbook publisher with a focus on science, he recruited Pauling to edit a series of chemistry books that he planned to publish over the next decade. In turn, Pauling entrusted his own coveted manuscript to Freeman as the first book to be released in this series and, ultimately, the first text that W.H. Freeman and Company would ever publish.

Intravenous Vitamin C: The Current Science

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Jeanne Drisko with Murray Susser. Both Drisko and Susser are past presidents of the American College for Advancement in Medicine.

[Part 2 of 2]

At her public lecture, “Intravenous Vitamin C: Does it Work?” delivered at the Linus Pauling Institute’s Diet and Optimum Health Conference in September 2017, Dr. Jeanne Drisko of the University of Kansas Medical Center, Kansas City, provided an overview of current research on the potential impact of intravenous vitamin C in treating disease.

She began this portion of her talk by reflecting on the factors that have continued to propel her own scientific interest in the topic, despite the headwinds generated by critics of the work. For one, Drisko has taken heart in the fact that intravenous vitamin C is used in many clinics around the world. Indeed, at a 2006 integrative medicine conference, Drisko and colleague Mark Levine took a survey of participants and found that some 8,000 patients had received intravenous vitamin C from doctors attending the meeting. Because Drisko maintains contacts in both conventional and alternative medical circles, she knows that naturopaths have been using intravenous vitamin C as well.

Drisko then pointed out that one barrier to more widespread acceptance of vitamin C as a cancer treatment is that, conventionally, it does not make sense to administer it in tandem with chemotherapy, since vitamin C is known to be an antioxidant and chemotherapy is a prooxidant. That said, Levine and Drisko’s colleague in Kansas, Qi Chen, have found that when vitamin C is given intravenously, it actually works as a prooxidant because it produces hydrogen peroxide. As such, it actually becomes a very good compliment to chemotherapy. Moreover, studies conducted by Drisko and others have found no evidence of conflict arising as a result of vitamin C dosages given alongside chemotherapy. On the contrary, researchers have reported a synergistic relationship in many cases.

In explaining why this is so, Drisko noted that when vitamin C is injected into a vein, it takes on the form of an ascorbyl radical, which she described as a “very promiscuous and active molecule that likes to interact with transition metals” like copper and iron. These interactions lead to the formation of hydrogen peroxide, which is quickly turned into water and oxygen by the enzymes glutathione peroxidase and catalase, such that levels of hydrogen peroxide in the bloodstream are promptly rendered as unmeasurable.

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However, when vitamin C gets into the extracellular fluid it also becomes hydrogen peroxide. The difference in this case is that glutathione peroxidase and catalase do not intervene and the hydrogen peroxide is not broken down into water and oxygen. Instead, the hydrogen peroxide diffuses throughout the extracellular fluid, bathing the cells.

While the presence of hydrogen peroxide in the cells might seem unsafe, Levine’s cell culture tests have found that hydrogen peroxide caused harm only to cancer cells. In reporting his results, Levine explained that the glutathione peroxidase and catalase enzymes are not as efficient in attacking cancer cells because they direct their activity towards reproduction rather than other processes. The fact that glutathione peroxidase and catalase are not active in the extracellular fluid renders vitamin C as a pro-drug and hydrogen peroxide as an actual drug.


Drisko’s research portfolio on the use of intravenous vitamin C includes the first randomized controlled trial involving ovarian cancer patients, work that was published in 2014. The trial studied two groups of patients: one group received standard care, which included carboplatin and paclitaxel chemotherapy for six cycles. The other group received this same care along with 75 to 100 gram doses of intravenous vitamin C.

The trial made clear that this form and dosage of vitamin C therapy is safe to administer. It also yielded a statistically significant improvement in how certain types of patients felt during their cancer treatment. Drisko called this a “feel good effect” which she believes is neurological. This same impact, however, was not observed in patients suffering from more advanced stage three and stage four cancers. Drisko is currently following up on these results by looking at the role that vitamin C might play in brain chemistry.

While her work has generated positive results, Drisko is also aware that vitamin C should not be used in all cases. Importantly, vitamin C is known to be potentially harmful when given in large doses under certain conditions. One such case is in individuals suffering from a deficiency of Glucose-6-Phosphate Dehydrogenase, or G6PD. On its own, G6PD can cause anemia, but when combined with high levels of vitamin C it leads to hemolysis, or the destruction of red blood cells. As a matter of standard protocol, Drisko checks her own patients for G6PD deficiencies, but she knows of others who have been unaware of this biological conflict and who have had to send patients to the emergency room.

Drisko will likewise opt against administering intravenous vitamin C when a patient reports a history of oxalate kidney stones, which can form as a result of excessive vitamin C intake. For individuals who have gone ten years or more since their last instance of oxalate kidney stones, Drisko administers vitamin C, but she does so cautiously, monitoring kidney functions and liver enzymes throughout the process.


Another barrier to studying intravenous vitamin C is that it is a difficult substance to measure since it is processed by the body so quickly. To get around this difficulty, Drisko developed a finger stick method that emerged from her interactions with a diabetic ovarian cancer patient. Over the course of these interactions, Drisko found cause to contact a glucometer manufacturer who told her that, because vitamin C and glucose molecules are so similar, the glucometer would indicate levels of both. Making use of this similarity, Drisko started taking finger stick glucose readings both before and right after her patients received their doses, and using this process she is now able to ascertain a rough estimate of how much vitamin C has been absorbed by the body.


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Qi Chen

In attempting to achieve greater certainty about appropriate dosage levels of vitamin C to administer, Qi Chen and Mark Levine have conducted experiments wherein they give intravenous vitamin C to mice and rats with tumors. This work is a follow-up to Levine’s original studies in the 1990s, which showed that vitamin C given orally could not be absorbed above a 10 millimolar concentration. In their more recent invesigations, Levine and Chen have found that blood concentration levels of 20 to 30 millimolar can be achieved as a result of intravenous application. They also found that the tumors in their mice studies would take up the vitamin C and that hydrogen peroxide formed in the tumors and subcutaneous tissue, but not in the blood.

Drisko gives her patients two to three infusions of vitamin C per week in advanced cases. Ideally, the vitamin C would be administered as the fluid loading dose for chemotherapeutic drugs, but it is often difficult to carry out both vitamin C and chemotherapy treatments on the same day because patients are already burdened by a busy treatment schedule and the facilities providing the two types of treatments are often not in the same location. (A new dosing device that attaches to the hip, developed by Channing J. Paller at Johns Hopkins, could help to get around some of these barriers.) Drisko’s treatment schedule uses a “stair-step” methodology wherein doses ranging from 0 to 100 grams are able to achieve 20 millimolar blood concentrations.

The appropriate duration of vitamin C treatment for cancer is still an open question. What is known is that it takes at least a couple of months before effects start to show. This stands in stark contrast to chemotherapy, which makes a much quicker impact.


Drisko concluded her talk by sharing the hopeful story of a woman who had participated in her ovarian cancer trial. This patient had been part of the group that had received the standard chemotherapy treatment only. She had subsequently relapsed very quickly and was believed to have only months to live. In her conversations with Drisko, the patient expressed a strong desire to live long enough to give her grandson a present at Christmas, and she requested that Drisko give her vitamin C in addition to her chemotherapy, since she was no longer part of the trial.

Initial CT-PET images showed that the woman was suffering from an accumulation of fluid, or ascites, full of cancer cells that were pushing against her organs. At the start of her intravenous vitamin C treatment in 2004, a second CT-PET scan showed both the malignant ascites as well as a residual tumor that could not be removed surgically.

Subsequent scans after Drisko began her treatment showed gradual improvement. In 2007, the pictures included fewer ascites and the tumor was somewhat smaller, trends that continued to be seen in 2012. By 2014, calcification appeared in the tumor and around the fluid, with further calcification showing in 2015. In essence, what the scans were revealing was an eight-year process of “turning her cancer into a scar.” While this is only a single example, it is a powerful one, and may prove to be harbinger of medical breakthroughs to come.

Intravenous Vitamin C: The Historical Progression

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Jeanne Drisko

[Part 1 of 2]

Jeanne Drisko, MD, Director of Integrative Medicine at the University of Kansas Medical Center, Kansas City, was a featured speaker during the public session of the Linus Pauling Institute’s Diet and Optimum Health Conference, held September 13-16, 2017.  She delivered a public lecture titled “Intravenous vitamin C and cancer treatment: Does it work?” Dr. Maret Traber, a principal investigator at LPI, introduced Drisko, describing her as a “leading expert on intravenous vitamin C.”

Drisko began her talk by tracing the history of vitamin C research, noting the ways in which previous studies had made her own research possible. The first person Drisko spoke of was Nobel laureate Albert Szent-Gyӧrgyi (1893-1986), who isolated ascorbic acid while working at Cambridge University and the Mayo Foundation between 1927 and 1930. Drisko then pointed out that, in the 1940s, vitamin C was used widely in clinical settings to treat pertussis, or whooping cough, along with other bacterial and viral infections. Importantly, these treatments were not administered orally. At the time, pharmaceutical preparations of vitamin C were not of a quality that could be administered intravenously, so they was injected into the muscles.

The use of vaccines was also on the rise during this period and Drisko pointed out that the development of the polio vaccine was particularly connected to the clinical fate of vitamin C. Albert Sabin (1906-1993), who had developed an oral polio vaccine, also carried out trials on the effects of vitamin C injections on primates. Sabin found no benefit and suggested that focus turn toward vaccines instead. It was at this point, Drisko explained, that the use of vitamin C injections went “underground,” drifting well outside of the medical mainstream.

One individual who remained interested in the promise of vitamin C was Frederick Klenner (1907-1984), who began using intravenous ascorbic acid at his North Carolina clinic in the 1940s. Drisko described Klenner as keeping “vitamin C use alive,” by administering both muscular and intravenous injections, while the broader medical community turned elsewhere. In particular, Klenner used vitamin C to treat children suffering from polio and found that even advanced cases could be approached successfully. During this time, Klenner also trained other practitioners in the methods that he was pioneering at his clinic.


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Ewan Cameron, Ava Helen and Linus Pauling. Glasgow, Scotland, October 1976.

Next, Drisko turned to Linus Pauling. To begin, Drisko noted that since Pauling was already well known, his interest in oral vitamin C was written off by many who were familiar with his prior work. Others, however, did look to Pauling as an authority, and among them was the Scottish surgeon Ewan Cameron (1922-1991), who contacted Pauling after reading some of his papers in the early 1970s. In his initial correspondence, Cameron informed Pauling that he had been giving about ten grams of vitamin C to cancer patients and had observed that they tended to live longer. As a result of their shared interest, Pauling and Cameron decided to collaborate on a series of papers investigating the potential clinical import of large doses of vitamin C.

As they delved deeper into this work, Pauling became convinced of the need to carry out more rigorous trials. Lacking the funds to do so, he instead turned to the National Institutes of Health. Fatefully for Pauling, Charles Moertel (1927-1994), an oncologist at the Mayo Clinic who was eager to debunk the effectiveness of vitamin C, agreed to lead the NIH investigation. Specifically, Moertel carried out a double-blind placebo-controlled trial in which ten grams of vitamin C were administered orally, and he found no benefit. (He was not aware that Cameron had been injecting vitamin C intravenously.) Moertel published his results in the New England Journal of Medicine and the press picked it up. Once the negative conclusion had been widely circulated, subsequent mainstream interest in the medical application of vitamin C suffered a near fatal blow.


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Mark Levine

Research on intravenous vitamin C began to re-emerge during the 1990s, led in part by NIH scientist Mark Levine. Levine’s nutrition experiments were novel, and did not emerge from the types of medical training that he could have been expected to received. For context, Drisko described her own education, wherein courses on nutrition were optional and held on Saturday mornings. She attended them because she was interested, but she also went along with the convention of the time; one emphasizing that nutrition was of lesser importance relative to other aspects of medical practice.

Levine, on the other hand, did not follow this line and decided to study vitamin C in depth. In the trials that he carried out at the National Institutes of Health, Levine tracked patients deprived of vitamin C and showed that they had indeed become vitamin C deficient. He followed this by administering oral doses of vitamin C, which demonstrated repletion. At the end of his trial, Levine also administered one gram of vitamin C intravenously. He was not allowed to administer a higher dose to his subjects, due to fears of toxicity, but it was his guess that ten gram doses would yield peak blood levels of vitamin C.

Ultimately, Levine demonstrated that oral vitamin C was not capable of yielding maximal vitamin C blood levels, because the body does not absorb oral doses well and excretes it very quickly. Intravenous administration, on the other hand, bypassed these metabolic processes, leading to higher blood levels. With Levine’s work in mind, Drisko summarized the difference between Cameron’s research and Moertel’s Mayo Clinic trial: “Cameron gave a drug and the Mayo Clinic gave a vitamin.”


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Hugh Riordan

Drisko’s mentor, Hugh Riordan (1932-2005), was another individual responsible for keeping vitamin C research alive. The founder of what is now known as the Riordan Clinic in Wichita, Kansas, Riordan belonged to a group of orthomolecular physicians who saw vitamins as providing restoration of a healthy baseline in all humans.

After Levine published his paper on vitamin C absorption, Riordan went to visit him in Maryland to convince him to continue following this path of inquiry. The two ultimately collaborated on several case studies and welcomed others into their fold, a progression that helped incubate today’s group of researchers investigating the use of intravenous vitamin C.

As of 2016, the intravenous vitamin C group included Qi Chen, who works on basic research at the University of Kansas with Drisko; John Hoffer at McGill University, who explores the effects of high doses of vitamin C on cancer; Garry Buettner and Joseph Cullen at the University of Iowa, who looks at the redox capacity of vitamin C in patients undergoing radiation therapy; and Ramesh Natarajan at Virginia Commonwealth University, who is researching the use of vitamin C in the treatment of sepsis.

Drisko noted that there are differences in the lines of research followed within the current group. On the one hand, her cancer trials use megadoses of vitamin C at 75 to 100 grams. Natarajan, on the other hand, only uses 4 or 5 grams in the ICU for sepsis.  For Drisko, these differences emphasize that there is still a lot of research to be done to understand exactly what is going on.


At present, attitudes toward vitamin C within the medical community can be mostly lumped into two categories. One is comprised of “early adopters,” as Drisko defines herself, who continue to carry out research to refine vitamin C treatments. The other consists of those who adhere more closely to the conclusions of the Moertel study, and who thus believe that claims supporting the effectiveness of vitamin C have been disproven. The distance between these two groups was characterized by Drisko as a “gulf of disapproval.”

However, current trends suggest that the gulf is being bridged. While some state medical boards still restrict the therapeutic use of vitamin C, Drisko and others have succeeded in garnering increasing levels of support from both colleagues and institutions. Shifts in funding opportunities are also beginning to emerge: though Drisko was unable to secure federal dollars for her work on ovarian cancer, the Gateway for Cancer Research non-profit stepped in to provide crucial support. With evidence of the efficacy of the treatment building from a growing number of trials, the possibility of obtaining federal grants is becoming more realistic. Likewise, drug companies are now looking at ways to patent vitamin C therapy, and some vitamin C treatment patients have succeeded in receiving reimbursement from their insurance companies.

Next week, we will provide an overview of the science underlying this renewal in optimism about the potential to fight disease with intravenous ascorbic acid.

Pauling’s OAC: Completing the Freshman Year

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President William Jasper Kerr speaks to members of the Students’ Army Training Corps, as assembled near the OAC bandstand, 1918.

[Part 4 of 4 in our series examining the Oregon Agricultural College that Linus Pauling knew during his freshman year, 1917-1918. Fall 2017 marks the 100th anniversary of Pauling’s enrollment at his undergraduate alma mater, known today as Oregon State University.]

Linus Pauling’s freshman year at Oregon Agricultural was spiced up a bit by a little administrative drama. Beloved OAC President William Jasper Kerr, who been appointed ten years prior in 1907, was being courted by Kansas Agricultural College, at that point the largest “aggie school” in the United States. An “insistent” Kansas board of higher education offered Dr. Kerr the presidency of KAC and a salary of $9,000 per year, compensation far beyond anything that OAC could propose.

The Kansas offer was met with heartfelt concern from OAC’s students, one of whom stated in a Barometer article that “every friend of the College hopes the President may decline the offer.” Of this moment, Pauling later recalled

Directly after I arrived in Corvallis, in the fall of 1917, there was a big rally with a couple of thousand of students marching down to the President’s House, singing songs that had been made up for the occasion, urging him to stay here instead of going to Kansas State College, in Manhattan, Kansas….that was one of my memories of one of the exciting events during my first year.

In December, the campus shared a collective sigh of relief when it became public that Kerr had decided to stay. Speculating about this turn of events, The Barometer suggested that “President Kerr’s decision seems to have been made chiefly on the grounds of the splendid opportunities afforded in Oregon through the cooperation of the able and united forces that have supported his administration.”

Kerr’s presidency would continue for another fifteen years, coming to a close only upon his acceptance of the position of Chancellor of the Oregon State System of Higher Education. His leadership was key to the success of OAC, which grew significantly during his years of service.


Pauling at track practice, Bell Field, Oregon Agricultural College. 1917.

Pauling hurdling at Bell Field during his short-lived track career, 1918.

Pauling came away from his first semester of college with five A’s, two B’s, and a D in Mechanical Drawing. (Of Pauling’s one notably poor mark during the term, biographer Tom Hager writes, “he wasn’t patient enough to let the ink dry on his work, Pauling remembered, and kept smudging it.”)

Spring semester for Pauling revolved around a heavy course load that included Integral Calculus, Descriptive Geology, French, and Qualitative Analysis. It was during this semester that he also received his only failing letter grade, the product of an unsuccessful attempt to circumvent the physical education requirement by joining the school track team. His try-out was, evidently, a mess, and he did not make the team. Once this gambit had failed, Pauling chose not to return to the Gym class in which he was enrolled, as his course load was proving to be quite heavy. (He took, and passed, the required class later on during his OAC career.)

Though encumbered by significant responsibilities outside of the classroom – including the lack of a permanent address and the need to work multiple jobs to make ends meet – Pauling completed his first year with seven A’s, one B, and two C’s – one in Descriptive Geometry and the other in Camp Cookery. The grade scale that OAC used at the time included a letter grade “E,” meaning that OAC marks of B, C and D were comparable to contemporary grades of A-, B+, and B-. As such, Pauling’s freshman academic record was really quite superb, both within his major and across the military and liberal arts courses that were required of him.

As Pauling’s academic excellence mounted, so too did the invitations to join a number of honor societies. By the time of his graduation in 1922, Pauling was a member of the Scabbard and Blade military honorary, and had served as secretary of the Sigma Tau engineering honor society, treasurer of the Chemical Engineering Association, and president of the Chi Epsilon civil engineering honor society.


 

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Two OAC classes battle in the tug of war, 1912. The competition was often held at the nearby millrace, with the losing class obliged to take a dip.

Socially, the 1917 school year broadly conformed to the calendars that had defined previous years, though a few changes were necessitated by World War I, particularly during spring semester 1918.

Because a significant portion of the men in the junior and senior class had left campus for Officers’ Training Camp, springtime saw a premature rendition of Junior Weekend. The commencing affair was “Junior Flunk Day,” while other happenings included the “Fresh-Soph Tug-of-War.” Pauling’s class, the freshmen, won this display of strength and, after watching this apparent disgrace, the juniors challenged the seniors and won. Junior Prom followed the tug-of-war and was treated as a sendoff for the young men leaving for the European theater. Previously a formal event, the conditions brought about by war rendered the 1918 Junior Prom more of an informal affair.

Outside of socializing on campus at dances and club events, students in Corvallis often entertained themselves with a night out. Popular activities included seeing movies at the Majestic Theater and ending the night with ice cream at Winkley’s Creamery. Another hot spot for spending time and grabbing a bite to eat was Andrews & Kerr, which served “Hooverized” waffles and offered a location where “seniors enjoyed high jinks.” Pauling was fond of A&K’s and frequented it when he could afford to, especially after seeing a show downtown.

The concluding social activities of the year transpired during Graduation Week and consisted primarily of events tailored to the graduating class. One notable highlight was the Senior Picnic Breakfast at A&K’s, complete with “bacon, coffee, oranges, eggs, buns, and doughnuts.” Other events included the dedication of the class monument and, as post-commencement exercises, an Alumni Ball and Banquet.

Overall, the 1917-1918 school year at Oregon Agricultural College was an eventful and productive one, if shadowed throughout by the specter of war across the Atlantic. The OAC to which Pauling had been introduced was a varied and multifaceted institution, buoyed by an enthusiasm for shaping students into engaged, innovative, and community-oriented citizens. These principles and this spirit left a mark on Linus Pauling, just as he made an impact on the college and, later, the world.

Rook Life

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Pauling outside his boarding house, first term of his freshman year at OAC.

[Part 3 of 4 in our examination of the Oregon Agricultural College that Linus Pauling came to know during his freshman year. Fall 2017 marks the one-hundredth anniversary of Pauling’s enrollment at OAC, known today as Oregon State University.]

Each year, students arrived from around the state, country, and abroad to attend Oregon Agricultural College. For the 1917-18 school year, OAC boasted a student body of over 4,00 men and women. Long requested by the student body, the number of college personnel also began to rise that year, with totals nearing 200 faculty members. And despite the onset of American involvement in World War I during the previous spring, OAC’s fall 1917 registration was its largest ever. Contributing to this was the fact that more women had enrolled for the 1917-18 school year than had ever previously been the case at the college.

One member of this large first-year class was a sixteen-year-old Portland resident, Linus Pauling. Once arrived in Corvallis, Pauling, in his diary, described his living situation, a boarding house close to campus, noting that “I have a nice big room, much larger than two boys usually have. I will share it with a sophomore named Murhard.” He likewise recorded these observations of two other young men sharing a room in the same house

they are two rooks; one, a 20 yr. old talkative fellow, named Hofman, weight 175# and always talks about his girl, Millicent, nicknamed “Titter.” The other, Henry, is a very quiet, small young man, but slightly deaf.  He will take Commerce, and Hofman will take Forestry.

Pauling left the boarding house after Fall semester and, because he was unable to find a permanent place of residence, he often wound up staying with friends during the Spring. Viewed through a modern lense, it would not be a stretch to say that Pauling was effectively homeless for this period of his studies at OAC.


Early on, Pauling expressed a great deal of insecurity in his potential to excel at the college. It did not take very long, however, before he discovered that his merit in academics had very clearly carried over from his high achieving ways in high school.

During the fall semester, Pauling registered for a typical collection of first-year classes, including Modern English Prose, Drill, and Gym. In addition, he began working through the core curriculum for Chemical Engineering majors, taking courses like General Chemistry, Mining Industry, and Calculus.

As he moved forward through his coursework, Pauling found that his high school education, though incomplete – he had not taken a required history class and did not graduate from Washington High School – was more than satisfactory. So pleased was he by the preparation that he had received for college, that he wrote a letter thanking his high school math teacher, Virgil Earl, for having done an exceptional job.

Earl replied to Pauling with gratitude and encouraging words, saying, “you have the ability and the disposition to work so I feel sure that you will succeed in your chosen work.” Earl’s point of view would soon be reflected by waves of praise and admiration extended by many of Pauling’s OAC professors.


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Pauling wearing his “rook lid,” ca. 1917.

Student functions played an outsized role in the undergraduate experience at Oregon Agricultural College. Activities and meetings were held each week and larger gatherings, such as dances, were hosted with great frequency.

Socially, the school year was underway once the YWCA-YMCA welcome reception had been hosted. This event, which was basically a dance, was put on by the two clubs to familiarize first-year students with the social dynamic of their new home. The 1917 welcome dance took place in the Men’s Gym (now Langton Hall) where the College president, William Jasper Kerr, kicked off festivities by addressing the assembled student population. The rest of October saw Mask and Dagger theatrical auditions, a senior reception held for the “frosh,” and an informal band dance. Class and student body elections also took place at the end of October.

In addition to cultivating a culture of of student involvement, the college did its best to stoke long-running social traditions. Pauling took these rituals seriously and commented on how they had strengthened his school spirit. By the end of his first month in college, he noted in his diary that “I am getting along alright. Have lots of beaver pep.”


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The Burning of the Green, 1925.

Central to many of these traditions was one’s class standing. First-year students were colloquially called “rooks” and “rookesses,” and were made to wear green caps (for men) or ribbons (for women) to denote their status. At the end of the year, students burned their “frosh” paraphernalia in a bonfire held just south of the Women’s Gymnasium.

Beyond hats and ribbons, amicable competitions and friendly rivalries between grade levels was an aspect of life at OAC which continued year round. Many of these events were staged during Homecoming, which took place annually during a fall weekend and focused intently on the college’s athletic teams as well as class rivalries. Sophomores and freshmen went head to head in both a bag rush and a football game, while all class levels participated in a three mile cross-country race. Intercollegiate sporting events during the 1917 Homecoming weekend included a soccer game between OAC and the University of Oregon, which O.A.C won, as well as a 6-0 home loss in football to Washington State College.

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The 1914 OAC Freshman-Sophomore Bag Rush.

The culminating event of the weekend was Sunday’s open house, during which undergraduates met and talked with alumni who had returned to campus. Of this experience the Beaver yearbook recounted, “all in all, it was a great success and the old fireplaces again welcomed familiar faces, and the undergraduates listened to stories of the ‘Good Old Times.'”

Another annual happening, The Co-Ed Ball, was held solely for the women of the college. Unsurprising, given the rising number of women attending OAC, 1917’s Co-Ed Ball was the largest in school history, with “four hundred women being present.” The supervisors of this specific occasion included Mary Fawcett, the Dean of Women, and Ida Kidder, the college’s beloved librarian, known to many as “Mother Kidder.”

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Performers in the Women’s Stunt Show, 1925.

The women of the College also sponsored the “Women’s Stunt Show,” for which every women’s organization on campus prepared and performed a skit. In addition to competing for a trophy, the Fawcett Cup, the ultimate goal of the Stunt Show was to raise funds. The 1917 edition succeeded on this front as a total of $400 was collected, with $200 apportioned to the YWCA.

In December, as the end of the term neared, the Intercollegiate Oratorical and Debate Society won its Annual Dual Debate against the University of Oregon. Other notable winter events included two Mask and Dagger shows: “Why the Chimes Rang” and “The Magistrate.” The Military Ball and the Interfraternity Informal rounded out a busy fall calendar for Linus Pauling and his fellow students at Oregon’s land grant college.