Out of Ashes, the Phoenix Rose

Linus Pauling Jr., October 14, 2011.

[Coda to our history of the Linus Pauling Institute of Science and Medicine]

Linus Pauling Science Center grand opening Keynote Address, by Linus Pauling Jr., MD. October 14, 2011.

This is a very personal account of the background that has miraculously led to this wonderful, beautiful and exciting building, I title it: OUT OF ASHES THE PHOENIX ROSE.

It was back in the spring of 1991, just over 20 years ago now, that I sat down to talk with my father at his Big Sur ranch on the rugged California coast. For many years, in fact since my mother died a decade earlier, my wife and I had made a pilgrimage to the ranch to be with my father and celebrate our three birthdays, which fortuitously fell within a two-week period.

I had been on the Board since the Palo Alto Linus Pauling Institute of Science and Medicine’s inception in 1973, so at our 1991 meeting I knew the situation had become desperate. My father, who for all his earlier life had been full of remarkable energy and ambition, now at 90 had lost that energy and was making mistakes in judgment. He was ill with the cancer that would kill him three years later.

LPISM was failing: half a million dollars of debt, laboratory research had vanished for lack of incentive and direction, donor income was being diverted to non-nutritional investigations, there were no research grants and morale was in the basement.

As his oldest son, I could not just stand by and watch this great man’s efforts of the past quarter century go down the drain, along with his reputation. If the Institute failed, all the naysayers would crow and describe him as a senile crackpot in spite of his astonishing lifetime achievements. Additionally, the thousands of donors over the years and the makers of future bequests would feel betrayed. It was obvious he needed help. As his son, I felt it was necessary to provide that help and it felt good to me to try.

So we had to talk. Early in my life I realized that my father was a very special person with talents I could never hope to emulate. That was emphasized by this story which I enjoy telling. When I was about 15, my father was writing an introductory chemistry textbook for Caltech freshmen, the best and brightest college freshmen, the cream of the crop. At the end of each chapter were questions. He asked me to read a chapter and answer the questions. I tried, valiantly, but I did not understand the text and could not answer a single question. When my mother heard about this, she hurried down to the Pasadena City Hall to have my name officially changed from Linus Carl Pauling to Linus Carl Pauling Jr. so no one could possibly mistake me for him.

At least I had sense enough to follow a very different track from my father, one that eventually gave me skills that now could be used to help him as my thanks to him for bringing me into the world.

It was now or never, so I boldly waded in. He and I discussed the future, starting with the past. I talked about his amazing life with his multiple triumphs in so many and so very diverse arenas.

His fame was world-wide, originating with the scientific community. I pointed out that he was arguably the first, and certainly the most successful, bridge-builder between chemistry, mathematics, physics, medicine and biology, linking these disciplines to create what is now the most popular science of all, molecular biology. One result of his creativity, hard work and dedication to science, as you all know, was the Nobel Prize for Chemistry.

It was during this time period that his interest in nutrition originated, spurred by his own life-threatening kidney disease. Thanks to a rigid diet prescribed by Stanford Medical School nephrologist Dr. Thomas Addis at a time long before renal dialysis, and carefully supervised by my mother, my father not only survived a usually fatal disease but recovered completely.

After World War II, prompted by my politically-liberal mother whom he certainly loved deeply and wanted to please, he embarked on a spectacularly successful two decades of humanitarian effort, educating the governments of the world and, necessarily, their peoples, about the evils of war and the dangers associated with unrestricted exposure to radiation, especially that produced by the hundreds of nuclear bomb tests being conducted. He suffered vilification by many from all parts of the world. He was hounded by the FBI and the United States government.

His crowning moment of glory, at least in my estimation, was his indomitable courage in confronting those nasty witch hunters, the United States Senate Internal Security Subcommittee, when facing imprisonment when he refused to disclose the names of his ban-the-bomb United Nations petition assistants. He knew that these conscientious people, most of them scientists, would be less able than he was to defend themselves from accusations and loss of employment. The Subcommittee, when faced by my father’s public popularity, courage, remarkable memory and command of facts, then backed off, their collective tail between their legs. His world-wide influence was so extensive and the result so positive that he was eventually awarded the Nobel Peace Prize.

So what was next for him? His old interest in nutrition as a factor in health and well-being resurfaced. Starting with vitamin C, he promoted nutrient research and encountered resistance from university, medical and government bureaucracies. He turned to the public, writing article after article and giving hundreds of talks, with the result of an explosion in popular food supplement usage. But research remained a fundamental necessity, so the private nonprofit Linus Pauling Institute of Science and Medicine was founded in 1973 and initially showed promise.

By the time of our talk in 1991, LPISM’s outlook was dismal.

At age 90, my father was tired and dispirited. Being fully occupied with his own illness, he was unwilling to devote energy to coping with his Institute’s problems. I said to him that I could not in good conscience stand by and see his eponymous Institute go down in ignominious defeat. With his incredibly illustrious past, I felt strongly that he deserved more than that. And maybe, just maybe, I could do something about it.

We decided, together, that if the Institute, and also his reputation, were to survive, the best course of action was for the Institute to affiliate with a reputable university. That would ensure the rigorous scientific attitude and protocol necessary to legitimize micronutrient research in the future. And, most important of all, we had to be ethically responsible to the thousands of past, present and future donors who believed in my father and supported the Institute. We could not let them down.

I had just retired from 35 years of the practice of psychiatry, so I had the time and energy to devote to other endeavors. After discussion with my wife, I decided to offer to take over management of the Institute. I had to have my wife’s agreement, because I was planning to spend considerable time in Palo Alto, a long way from my home in Honolulu.

To his credit and with an audible sigh of relief, my father agreed. We discussed affiliation possibilities, Stanford and Caltech among them. He seemed, however, to favor Oregon State University, his undergraduate alma mater, to which he had already committed his scientific papers. If you haven’t already, you should check out the Pauling Papers at the OSU Valley Library Special Collections website. You will be impressed.

During the next years, I became President and Chairman of the Board of LPISM. We reorganized radically and survived many trials and tribulations. My essential second in command Steve Lawson and I visited many universities.

OSU, thanks to then President John Byrne, Development Director John Evey and Dean of Research Dick Scanlan, was our clear and undisputed choice.

And what a great choice it was! Here now, before us, 15 years later, is the Linus Pauling Science Center, dedicated to highest-quality research in scientific areas that would surely be of interest to my father. I’m sure, if he were here, he would have tears of joy in his eyes just as I do.

I want to thank OSU President Ed Ray, Dean Sherman Bloomer, LPI Director Balz Frei, architect Joe Collins, the many others in the system who have participated in making this possible, all the donors and the people of the great state of Oregon. I specifically thank the key major donors, Tammy Valley and Pat Reser, for allowing Linus Pauling’s name to be on this beautiful building. That is a very unusual act of generosity.

It will be a great future. Thank you all with my whole heart.

The Paulings and Unitarianism

Stephen Fritchman and Linus Pauling, La Jolla, California. 1969.

“In Unitarianism I have found a religion without dogma: A growing, changing, open-minded willingness to learn and, above all, to work.“

– Ava Helen Pauling, “Why I am a Unitarian,” September 18, 1977.

Though both Linus and Ava Helen Pauling were avowed atheists,  they did maintain a long and friendly relationship with the Unitarian Church.  This relationship was rooted in their friendship with Stephen Fritchman (1902-1981), a Reverend of the Unitarian Church of Los Angeles, as well as an active and influential member of several peace-oriented organizations.

When Linus and Ava Helen joined the Hollywood Council of the Arts, Sciences and Professions in 1945, Fritchman held one of the vice-presidencies of the organization. Though they were familiar with Fritchman in this regard, the Paulings did not become better acquainted with him until after the memorial service for Linus Pauling’s trusted physician and friend, Dr. Thomas Addis, who died in 1949.

In the early 1940s, Pauling was diagnosed with glomerulonephritis, a condition that most doctors at the time considered fatal. Pauling was referred to a specialist, Dr. Addis, whose alternative treatment is widely credited with having saved Pauling’s life. The respectful and dignified memorial service that was held by Rev. Fritchman for Dr.  Addis left the Paulings feeling comforted, hopeful and interested in the Unitarian Church itself.

Both Linus and Ava Helen had rejected organized religion at very young ages. Notions of an anthropomorphic god and salvation dependent on intercession from a third party were discarded, in favor of a doctrine of reason, ethics and morality. In various interviews over the the years, both of the Paulings evinced similar reasons for joining the Unitarian church, but took great care to mention that a creed or means of salvation were not among them.

To this end, Ava Helen once listed seven principles of Unitarianism, formulated by a Unitarian committee in 1930, to highlight the similarities of outlook between science, Unitarianism and her own personal beliefs. They included:

1. Use of scientific method in approaching religion.
2. Rationality of the universe and progressive discovery of truth.
3. Humility and reverence toward vaster forces of the universe.
4. Conviction of infinite possibility of human progress.
5. Free exercise of intelligence in religion.
6. Conviction of self-sufficiency of humanity to solve its problems.
7. Sense of human brotherhood.

Linus Pauling claimed on several occasions to enjoy his independence within the peace movement, but he was also very fond of the connections that he sometimes made with the “like-minded individuals” representing any number of peace-oriented organizations. As with his participation in many other peace- and science-related activities, Pauling’s involvement in the Unitarian church offered an opportunity to network, share ideas and practice public speaking.

When Dr. Pauling spoke of the value of certain religiously oriented institutions, he sometimes likened them to gaps which he felt science could not fill. In a speech crafted for the First Unitarian Church of Los Angeles in 1969, Pauling observed that “despite our increasing power over nature, the amount of suffering in the world remains very great…The major reason for the continued misuse of our power over nature, for the continued existence of a great amount of human suffering, is that the world is not operated on the basis of an accepted ethical principle.” Though he was openly averse to supernaturalism, mysticism and dogmatism, Pauling was a humanist who believed that both humanism and modern Unitarianism were rational philosophies that could be a source of good in the world.

In due course, the Paulings became active church members, and Linus was invited to join the Unitarian Service Committee, a “nonsectarian, voluntary agency whose purpose [was] to promote human welfare through service.” The Paulings also came to greatly admire Rev. Fritchman’s tolerance of diverse opinions, his respect for individualism and what they often referred to as his “great social conscience.”

Soon after the resolution of Linus Pauling’s initial bout of passport problems, Fritchman himself was denied a passport to Australia, where he was scheduled to speak at a Unitarian celebration. Pauling wrote a letter to the State Department, protesting the passport denial. In Fritchman’s defense, Pauling wrote:

I have known Mr. Fritchman for several years. I consider him to be a great man. He is one of the most honest, forthright, straightforward and high-principled men that I have ever known. He is an honor to the United States of America – the world would be a great world indeed if one percent of its people were comparable to Mr. Fritchman.

During the 1950s, the Unitarian church became embroiled in a controversy involving California loyalty oaths. A case condemning the group was brought to trial, but the church was eventually vindicated by a United States Supreme Court ruling. This event, among many others, did much to strengthen the bond between the Paulings and the church.

Above all, Linus and Ava Pauling found in Unitarianism a unique forum to fight against the grave problems facing the world. Their participation in the church was not often separated from fervent activism or an acknowledgment of difficult political realities. The connections that they made fit well into their condemnation of war, nuclear proliferation, militarism and inequality.

Nephritis Today

Dr. Barry Brenner

[Part 5 of 5]

Currently in western medicine, it is believed that nephritis is caused by a variety of health conditions ranging from acute infections to autoimmune disorders. Modern therapies include corticosteroids, immunosuppressant drugs, antibiotics, plasmapheresis, renal dialysis, and kidney transplants. Corticosteroids reduce inflammation of the kidneys and immunosuppressant drugs are prescribed to limit the immune response that causes the inflammation. If the cause of an individual’s nephritis is known to be bacterial, antibiotics are administered. In severe cases that progress rapidly to kidney failure or end stage kidney disease, plasmapheresis, renal dialysis, and kidney transplants are prescribed.

The exact cause of Linus Pauling’s nephritis is unknown. While Thomas Addis’s low-sodium, low-protein diet appears to have been successful in Pauling’s treatment, his radical dietary therapy for nephritis lost popularity within the United States shortly after Dr. Addis’s death. The dietary treatment was quickly replaced with steroid therapies and renal dialysis.

The medical community seems to have lost interest in Dr. Addis’s dietary therapy until an article was published in the New England Journal of Medicine in 1982. With a fresh outlook on the potential of a low-protein diet in the treatment of glomerulonephritis, the medical community’s consideration of Addis’s dietary regimen peaked once again.

The primary author of the 1982 publication, Dr. Barry Brenner, further developed Addis’s theory, providing additional insight into the progression of damage to the glomeruli caused by nephritis.

Using rats as a model, Brenner determined that upon the onset of damage to the glomeruli (the small capillaries), all remaining healthy glomeruli begin overcompensating for the lost filtration function. By elevating internal pressure, filtration through the remaining functioning glomeruli increases. This overcompensation has severe consequences on the healthy glomeruli. As the healthy glomeruli continue to compensate they undergo increased stress causing wear-and-tear on their structure, which ultimately results in additional damage to the remaining functioning glomeruli. Brenner termed this form of compensation “hyperfiltration.”

In revisiting Addis’s proposed low-protein remedy, Brenner and his laboratory team determined that a protein-restricted diet reduces the kidneys’ overall workload, and thus decreases the stress caused by such hyperfiltration. Since the consumption of proteins increases the amount of filtration required of the kidneys, a low-protein diet reduces the kidneys’ workload and thereby decreases further damage to the remaining healthy glomeruli.

Brenner’s work was well received and current treatment plans, once again, often include dietary restriction of protein, sodium, and potassium, in addition to the other aforementioned modern therapies.  Whether commonly recognized or not, Thomas Addis’s pioneering research on diseases of the kidney – research which, in the early 1940s, saved Linus Pauling’s life – is still making an impact today.

Ava Helen’s Role in the Nephritis Story

Ava Helen Pauling serving food at the Caltech Chemistry Department picnic, 1941.

[Part 4 of 5]

“This is the record of the diet which Linus ate when he was ill with nephritis. I kept the record and noted everything that he ate. Dr. Thomas Addis of the Stanford Medical School was his physician.”

-Ava Helen Pauling

While Thomas Addis is rightfully credited with Linus Pauling’s recovery from nephritis, Addis himself preferred to place the acclaim elsewhere. Addis knew that he was not alone in his efforts to prevent the early demise of the great Linus Pauling and he recognized that he had a female cohort who was essential to Pauling’s care. Her name was Ava Helen Pauling.

Over the course of his practice, Addis relied heavily on the support of his patients’ families and was convinced that their efforts were vital to his patients’ care. In fact, Addis once said that it is the “…wives, mothers, and sisters who, with our patients are our true colleagues with whom we work and for whom we work.” Ava Helen was clearly no exception.

It did not take long for Addis to acknowledge Ava Helen as his colleague. Throughout Linus’ recovery, Ava Helen and Addis sent correspondence back and forth updating one another on Pauling’s status. Addis even signed his letters addressed to Ava Helen as “Your ever faithful collaborator, T. Addis,” and Ava Helen often referred to Pauling as “our patient” in her responses back to Addis.

Ava Helen Pauling to Thomas Addis, May 20, 1941, pg. 1

Ava Helen Pauling to Addis, pg. 2.

As soon as Pauling began the low protein, low sodium diet that Addis had prescribed, Ava Helen diligently kept a record of Pauling’s diet. This journal can now be found in the OSU Library Special Collections.

The notebook is meticulous and thorough. Occasionally, Ava Helen even includes small notes about Pauling’s health and daily activities.

Ava Helen began the record of Pauling’s diet on April 9th in 1941. In each of her entries, Ava Helen documented what and how much her husband ate, as well as the protein content (grams), the salt content (milligrams), and the calories in all that he consumed. She totaled the amounts after each meal and recorded final totals at the end of each day.  With the support of his loyal and dedicated wife, Pauling was able to stay on this strict diet for fifteen years.

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The following is a brief summary of Pauling’s low protein, low sodium diet, based on Ava Helen’s record.

Each day while on his special diet, Pauling consumed between 2,000-3,000 calories (usually closer to 3,000), around 55 grams of protein, and approximately 1.2-1.6 grams of salt.

His breakfasts typically consisted of a citrus fruit or glass of fruit juice, a cereal (shredded wheat, pancakes, or crepes suzette), milk, cream, and a cup of coffee.

For lunch he generally ate various combinations of the following:  eggs, vegetables, water biscuits, apple sauce, potatoes, cheese, fruits, and vegetables.

Lunch was often followed by a chocolate bar. From April 9th-June 30th, 1941 Pauling consumed some 65 chocolate bars.

In the evenings he would dine on fruits and vegetables, cheese, water biscuits, baked potatoes, and milk.

Below is an example of a typical day on Pauling’s nephritis diet.

Meal record kept by Ava Helen Pauling for April 23, 1941.

Wednesday, April 23, 1941

Breakfast

• 1/2 Grapefruit
• 6 Pancakes
• 2 Squares of Butter
• 6 Tbs Syrup
• 2 Tbs Cream
• 1 Cup of Coffee

Breakfast Total: Protein 11 g; Calories 1,050; Salt 259 mg

Lunch

• 1 1/2 Cup Eggnog
• 1 Piece of Coconut
• 1 Medium Orange
• 1 Medium Pear
• 1 Chocolate Bar

Lunch Total: Protein 20 g; Calories 858; Salt 543 mg

Dinner

• 1 Baked Potato
• 1 Square Butter
• 2/3 Cup of Cabbage
• 1 Cup of Milk
• 1/2 Cup of Gelatin
• 1/4 Cup Cream (30%)
• 4 Cookies

Dinner Total: Protein 19 g; Calories 830; Salt 510 mg

Daily Total: Protein 54 g; Calories 3,020; Salt 1312 mg

It is apparent that Pauling had a sweet tooth as his dietary record is littered with notes of sugary treats such as custards with chocolate sauce, sponge cakes, meringues, ice cream, fruit tarts and pies, puddings, cookies, Coca Cola, and strawberries with cream.

This dietary record is a unique window into an important chapter of the life of Linus Pauling.

The Methods of Thomas Addis

Portrait of Thomas Addis by Marion C. Raulston, held in the Thomas Addis Papers, Lane Medical Library Special Collections, Stanford University.

[Part 3 of 5]

“[In the beginning] I was all set on measuring things and was trying to be ‘scientific.’ But anyone who has patients and patience can scarcely help coming at last to see that experiments that don’t answer questions about patients are, for the doctor, pretty irrelevant.“

-Thomas Addis

The result of a lifetime of work devoted to the study of kidney disease, Thomas Addis became the first true American nephrologist. In studying the urinary contents of both healthy individuals and individuals affected with Bright’s disease, Addis was able to develop a systematic treatment plan unlike any other proposal of the time. As a clinical investigator Addis provided for his patients what most other kidney specialists at the time could not – hope and options.

Throughout his career, Addis consciously integrated his laboratory research into his clinical practice by methodically “mixing patients with rats.” In his effort to thoroughly understand the kidney and its diseases, Addis followed a group of nephritics for over thirty years while also maintaining a colony of over 1,000 rats for in vivo experimentation. Addis refused to separate his clinical work from his laboratory studies, and even went so far as to see his patients in a small cubical in the corner of his laboratory.

From his laboratory experiments and clinical experiences, Addis developed a unique method for the treatment of nephritis. Based on the physical concepts of work and healing, Addis believed that in order for the kidneys to recover, the patient must allow the organs time to rest. In pursuit of a reduced renal workload, Addis prescribed a low protein, low sodium diet for his nephritic patients. This method appeared to have worked effectively for the treatment of many (but not all) of Addis’s patients and proved to be the answer for Pauling’s ailments.

Addis’s system for treating nephritic patients relied heavily upon a series of quantitative measurements that soon became known as the “Addis count” and the “Addis urea ratio.” The “Addis count” quantitatively determined the number of red blood cells, white blood cells and casts (clumps of red and white blood cells) excreted in the urine. The “Addis urea ratio” measured the concentration of urea in the urine. These two measurements, in addition to a measurement of the total urine output, were the basis for Addis’s assessment of a patient’s progress throughout treatment. Addis believed that these measurements provided insight into both the nature and extent of the disease.

When Pauling came to Addis in 1941 for assistance with his diagnosis of Bright’s Disease, Pauling was quickly impressed by Addis’s methodology. Beyond the measurements described above, Addis qualitatively examined the cells obtained from the urine sample and identified any deformations and abnormalities that he observed.

Although Addis relied heavily on his laboratory group, he took all of the measurements and conducted the sample analyses himself, adamantly insisting that in order for the work to have meaning, the physician must be responsible for all of such analyses.  Upon gathering sufficient data, Addis used his qualitative and quantitative findings, as well as his experience with his patients, to clinically reclassify Bright’s disease and develop tailor-made treatment plans.

While Addis’s treatment offered relief to many, his findings and conclusions were often criticized by the scientific community for lacking validity. These critiques stemmed from Addis’s refusal to use controls in his clinical studies. In a note written by Pauling about Addis, Pauling proclaimed, “The trouble with Addis – no controls!” Addis firmly believed that controls in his research would be unethical. His duty, he wrote, was “to treat each patient in the way that I think will do him the most good.”

Were Addis to have incorporated controls into his clinical research, he would have been forced to split his patients into two groups. This experimental design would have left half of his patients without the treatment that he, as their physician, believed to be most effective. Addis considered such methodology to be unacceptable. As such, because Addis refused to include controls in his research, the majority of the scientific community considered there to be significant limits to Addis’s contributions.

Thomas Addis: The Man Who Saved Pauling

Thomas Addis, 1920s

[Part 2 of 5]

When Linus Pauling received his diagnosis of Bright’s disease in March of 1941, his prognosis was grim. At the time Bright’s disease was considered to be fatal and the majority of the medical community was in agreement that there was no cure or effective treatment. Fortunately for Pauling, a man by the name of Dr. Thomas Addis did not agree.

Thomas Addis, known to close friends and colleagues as Tom, was born on July 27, 1881 in Edinburgh, Scotland. After fulfilling a position as a Carnegie Research Scholar and Fellow, Addis left Europe in 1911 to pursue a career as clinical investigator at Stanford Medical School. Upon arriving in the United States, Addis devoted his life’s work to the study of kidney disease. By the time of his death at age 67, Addis’s achievements were such that some would refer to him in reverent tones. In the estimation of William Dock, an MD at the State University of New York, “As a medical scientist he was in a class by himself.”

Addis’s accomplishments placed him in a league of his own as a medical investigator and his persistent advocacy for his patients made him a superior clinician. This combination accounts for his recognition as a superior clinical investigator.

During his lifetime, Addis published more than 130 scientific papers. He also published two books on renal disease, The Renal Lesion in Bright’s Disease (1931) and Glomerular Nephritis: Diagnosis and Treatment (1948), both of which were well received in the medical community. Stanford University Medical professor Arthur Leonard Bloomfield would recount:

Addis’s book with Oliver on the renal lesion in Bright’s Disease is, of course, a classic, but the little volume on glomerular nephritis completed only a few months before his death seems to embody his philosophy of disease and of science in general; it will perhaps interpret the man to his followers better than anything else he has done.

Known for his unique laboratory structure, Addis strongly encouraged the collaboration of all members of his scientific team and managed his laboratory based on what he believed to be “democratic centralist principles.” Among his co-workers was Elesa, a lab dietician and Addis’s wife.

Throughout his career, Addis’s loyalty to the group as a whole never wavered. People’s World writer, Pele Edises, once requested a “profile interview” with just Addis, to which he replied, “Why can’t you just write about the lab and leave me out of it?” Addis was often described as a man of integrity and would most surely have disapproved of this blog post had his group members and their contributions not been mentioned.

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Over the course of Pauling’s treatment, he and Addis became scientific colleagues and good friends. Beyond their shared professional interests, Pauling and Addis also maintained characteristically active political minds. Outspoken in his beliefs, Addis’s political affiliations led him to assume a position as the founder and chairman of the San Francisco Chapter of the Spanish Refugee Appeal. A primary activity of the Appeal was to assist the funding of a clinic in Toulouse, France, known as the Varsovie Hospital, dedicated to the care and rehabilitation of Spanish Republican refugees.

Like Pauling, Addis’s political inclinations met with significant resistance throughout his professional career. In a note that Pauling dictated in preparation for an Addis memorial, Pauling noted that Addis’s affiliation with the American Medical Association (AMA) had been turbulent throughout his lifetime due to his political allegiances. In one instance Addis raised objections to the AMA’s California Medical Association’s support of a coffee cancer cure which Addis believed to exploit individuals seeking treatment. In another incident Addis spoke out against a $25.00 contribution requested or required by the AMA to fund a fight against President Truman’s system of medical insurance.

Thomas Addis passed away on June 4, 1949, in Cedars of Lebanon Hospital in Los Angeles. His death was mourned at home and abroad – the October 1949 newsletter of the Varsovie Hospital includes this passage:

Con la muerte del Dr. Thomas Addis, los antifranquistas, los republicanos españoles, perdemos un gran amigo y un valiente luchador en defensa de nuestra causa, por la República, por la Democracia y por la Paz. [With the death of Dr. Thomas Addis, the anti-fascist Spanish republicans lost a great friend and a valiant fighter in the defense of our cause, for the Republic, for the Democracy, and for peace.]

In his honor a new laboratory was added to the out-patient clinic of the Varsovie Hospital in 1950. And long after his death, Addis’s name was used effectively to raise funds for the clinic and to provide aide to the Spanish refugees who were victims of the Franco regime. In a March 1950 letter to Ava Helen Pauling, Addis’s former secretary, in commenting on the Paulings’ political stands, noted “how happy and proud Dr. Addis would be, could he know.”

The Thomas Addis Memorial Award, 1955.

In 1955 Linus Pauling was awarded the first Thomas Addis Memorial Award by the Los Angeles Chapter of the National Nephrosis Foundation. The award would evolve into an annual honor granted in recognition of significant contributions to the study of the kidney and its diseases.

After Addis’s death, Pauling offered to write a memorial detailing Addis’s life and accomplishments. In response, the Addis family prohibited any mention of Addis’s political affiliations, for fear of their personal safety, given the nation’s current political climate. As a result Pauling and his co-author, Dr. Richard Lippman, made the executive decision to delay publication. In Lippman’s estimation, “It is impossible to characterize Dr. Addis in my opinion, without some discussion of his political ideas and his philosophy of politics and people.”

A revised version of the piece, co-authored by Pauling and Kevin Lemley, would not appear in print until 1994, the year of Pauling’s death.

Pauling’s Battle with Glomerulonephritis

Pauling family portrait taken in 1941. Back of photograph is annotated, "1941. Daddy very ill."

[Part 1 of 5]

On March 7, 1941, Linus Pauling stood before distinguished colleagues prepared to deliver an address in response to his receipt of the prestigious William H. Nichols Gold Medal, presented by the New York chapter of the American Chemical Society.

Before Pauling began his recitation, he spoke candidly to his audience. He thanked the award committee for his selection and expressed gratitude that the acceptance of this award had provided him with an opportunity to reconnect with old friends.

On this rare occasion, however, it was apparent to all in attendance that Pauling’s physical health was suffering. His face was bloated and he reportedly lacked the enthusiasm that he was so well known to exude. Addressing the observations of many of his peers, Pauling joked, “Several of [my old friends] said to me tonight that I appeared to be getting fat. This is not so.”

Just that morning, Pauling had awoken to find his face so bloated that his eyes were nearly swollen shut. His tongue felt enlarged and his voice was flat. Over the previous few weeks, Pauling had been experiencing noticeable swelling, weight gain, and chronic fatigue but he could not identify the cause of his ailments.

With his audience, Pauling half-heartedly pondered over the cause of his puffed-up appearance. He compared the experience to childhood memories of unfortunate encounters with poison oak.

Yesterday I must have bumped into something similar…while I was wondering what the responsible protein could have been, I decided that it was a visitation – that I was being punished for thinking wicked thoughts.

The following evening Linus and Ava Helen had dinner at Alfred Mirsky‘s residence. Pauling was examined by another guest at the dinner party, Dr. Alfred E. Cohen, a cardio specialist from the Rockefeller Medical Institute. After ruling out problems with Pauling’s heart, Dr. Cohen remained perplexed by Pauling’s condition. Nothing appeared to be wrong with the forty-year-old man other than his extreme edema. Concerned by the severity of the swelling however, Dr. Cohen recommended that Pauling come into his office the following day for a more thorough examination and lab work-up.

Adhering to the physician’s recommendation, the Paulings met Dr. Cohen in his office at the Rockefeller Medical Institute the next day. After a battery of lab tests, Pauling was diagnosed with Bright’s disease – a potentially fatal renal disease that results in the degradation of the kidneys. At the time, little was known about Bright’s disease and the majority of the medical community considered it to be a terminal condition.

After receiving this diagnosis, Pauling was fortunately referred to a leading specialist in renal diseases, Dr. Thomas Addis, head of the Clinic for Renal Disease at Stanford. Dr. Addis was a pioneer in the field of nephrology and his treatment plan, at the time, was new and revolutionary. Had Pauling not been referred to Dr. Addis’ care, the treatment he would have received elsewhere would almost surely have killed him.

Under the guidance of Dr. Addis, Pauling’s condition was effectively treated by alternative means – a low-protein, low-sodium diet – rather than the polysaccharide infusions that would have reduced his edema but done little to improve his health.  By May, Pauling reported improvements in his overall well-being and by August, the edema had completely disappeared.

Since Pauling’s time of diagnosis, Bright’s disease has been reclassified and redefined. Now it is believed that Pauling was affected by what is currently termed acute glomerulonephritis.

Acute glomerulonephritis is characterized by inflammation of the kidneys due to an immunological response. Damage to the small clusters of capillaries within the kidney, known as glomeruli, results in what can most simply be described as a “leaky kidney.” When the glomeruli are damaged, proteins leak from the bloodstream into the urine through the damaged portions of the kidney. Thus glomerulonephritis consequentially leads to excessive protein loss. Glomerulonephritis profoundly effects the body’s ability to function, because the nephritic kidneys are unable to properly filter the blood.

In his 1941 speech, Pauling had wondered aloud about a protein that was responsible for his swollen condition. The culprit protein can now perhaps be identified as albumin. As proteins leak from the bloodstream into the urine, blood proteins, called albumin, exit the bloodstream. These proteins are known to be essential in the regulation of blood osmotic pressure. Without sufficient albumin in the bloodstream, the body becomes incapable of efficiently extracting excess fluid from the body cavity. This excess fluid then remains trapped in the body and ultimately results in excessive swelling – such as the bloating that Pauling experienced in 1941.

Although the albumin did not cause Pauling’s condition, the loss of this blood protein due to the nephritis appears to have resulted in the symptoms that he was experiencing at his award ceremony. Therefore, contrary to his original speculation, it was the absence, rather than the presence, of a protein that caused his extreme fluid retention.

Over the next series of posts, we’ll explore the details of Pauling’s battle with this frightening disease, and learn more about the people and methods who saved Linus Pauling’s life.

Linus Pauling Day-by-Day: The Internet Just Became A Bit More Crowded

23,000 pages of Pauling

In 1999 we hatched the crazy idea of trying to document every day of Linus Pauling’s professional life. Researchers were, at the time, honing in on a draft of the human genome, and our thinking was, if scientists can map the exact genetic details of human existence, why can’t we map the daily activities of Linus Pauling? So began the project now known as Linus Pauling-Day-by-Day.

Fast forward to this past Friday, and thirty years of the project have been completed. The Pauling Day-by-Day calendar now closely details Pauling’s every letter, manuscript, speech and travel itinerary for the years 1930-1959. It is plainly relentless in scope – in its current form, the site comprises over 23,000 static html pages and incorporates over 68,000 document summaries.

Bits and pieces of Linus Pauling Day-by-Day have been released over the past several years, usually in conjunction with the launching of a new Pauling-related Documentary History website. This latest iteration of the calendar, however, marks the first time that the project has been presented as a cohesive whole. The launch also includes a number of important new features.

Five More Years

The Day-by-Day site data now includes new event listings for the period 1955-1959. These were important years for Pauling in that he completed a tremendous amount of good work and also endured a tremendous amount of hardship for the outspoken political views that he had assumed since the close of World War II. In the late 1950s, Pauling published major work on the structure of silk fibroin, the nature of mental deficiency and the theory of anesthesia. During this time, he and Ava Helen also collected signatures for their famous United Nations Bomb Test Petition, visited Albert Schweitzer at his compound in French Equatorial Africa, and were excoriated for their activism on any number of occasions, including an infamous appearance on “Meet the Press.”

Index Pages

Pauling Day-by-Day now has a proper homepage and is key-word searchable (though, at the time of this writing, our search engine hasn’t quite completed indexing the site). Likewise, each year of the calendar has its own mini-homepage, featuring a full accounting of the Paulings’ travel for that year as well as an overview of the year’s activities as written by Pauling biographer Robert Paradowski. The navigation tools provided to move within and between years are also greatly improved.

The Day-by-Day Index Page for 1950.

Nearly 1,700 Illustrations

Possibly the most significant new addition is the incorporation of almost 1,700 digital objects used to illustrate each week of Pauling’s activities; or, in the case of 1954, his first Nobel year, each day. In prior calendar releases, only the first page of each illustration was made available. Now, the entirety of virtually every document scanned into the calendar is accessible to the user – the illustrations have been transformed from pictures (by definition) to true digital objects.

This key bit of functionality has afforded us great leeway in featuring items from the collection that would not normally have a logical home within our web presence. Naturally many of the more-expected components of Pauling’s biography are illustrated: his passport problems, his first Nobel trip to Stockholm, his administration of ambitious programs of scientific research. That said, we are now able to incorporate items that are, perhaps, a little bit on the unexpected side.  To name a few:

• Pauling’s proposed research on gout; an idea on desalinating ocean water using atomic energy; a well-researched complaint about the water pressure in his home.
• A meeting with Albert Einstein; suspicions about the advertising claims being made by Canada Dry; quibbles with American Tourister about the design of his and Ava Helen’s new luggage.
• Got a broken bone? Consider gluing it back together.
• Interested in cute baby pictures? We have those too.

Peter Pauling, 1931.

Almost 2,000 Full-Text Transcripts

Another exciting component of this version of Pauling Day-by-Day is our incorporation of a massive cache of full-text correspondence and manuscripts transcripts. Every 1930-1959 letter ever digitized by the OSU Libraries Special Collections is included, as are many of the letters written between Linus Pauling, Ava Helen Pauling and their children.

In turn, we are able to follow the development of, for instance, the family’s shared obsession with cars.

We are also able to stumble across important historical fragments as they played out in real time. Consider this item, the manuscript that Pauling used to accept the William H. Nichols Medal from the New York Section of the American Chemical Society. (the transcript is here) In the opening paragraphs of his talk, Pauling notes

I am happy also that this occasion has brought me in touch with many old friends – with Paul Emmett and Joe Mayer and many others. Several of them said to me tonight that I appeared to be getting fat. This is not so. You know, when I was a boy in Oregon I used to go around a great deal in the green, damp Oregon woods, and I always came into contact with poison oak, which caused my face to swell and my eyes to swell shut, and me to apply so much lead acetate solution that it is a wonder that I didn’t die of lead poisoning. Yesterday I must have bumped into something similar, for my face began to swell, and I began to be afraid that I would have to speak here tonight with my eyes swollen shut – which I could have done, with the practice I have had speaking in the dark.

The true nature of Pauling’s condition was, however, far more serious than poison oak. As Paradowski notes in his chronology

After the ceremonies, Linus and Ava Helen are at the apartment of Alfred Mirsky, and Dr. Alfred Cohn, a professor at the Rockefeller Institute for Medical Research, learns of Pauling’s condition and asks to examine him. The next morning, Cohn and some other doctors, after performing various tests, diagnose glomerulonephritis, a renal disease characterized by the abrupt onset of facial edema and hypertension. They ask Pauling what he plans to do. Pauling replies that he intends to go to the Mayo Clinic where he is scheduled to give a memorial address. One of the doctors advises Pauling to cancel the speech and return to California, where he should get in touch with Dr. Thomas Addis in San Francisco, a specialist in the treatment of nephritis.

On March 10, Linus and Ava Helen return to Pasadena. He arranges to see Addis, and, within a short time, Addis begins treating him. (He later tells Pauling that it was extremely fortunate that he did not go to the Mayo Clinic, because the doctors there would have pumped him full of a natural polysaccharide, and his edema would have disappeared, but he would have been dead in a little while.) Pauling is put on a low-protein diet and takes various vitamins and liver extracts.

Interested readers are, naturally, able to follow the progression of Pauling’s return to health, a process documented by letters from Ava Helen to Dr. Addis as well as a full accounting of Linus’s meals during the early months of his combating the disease.

Calendars retracing the daily activities of important figures were once a relatively popular component of the archival discipline. With time the sheer labor involved in compiling these types of resources rendered them impractical for most Archives and Special Collections.

We, however, feel that Linus Pauling Day-by-Day is a worthwhile enterprise for at least a couple of reasons. For one, it gets used – the site has garnered well over 17 million pageviews since its first two years were released in 2003, and many of our reference requests are generated by content included in the project.

Perhaps more importantly, we view the Pauling Papers, at 4,400 linear feet, to be more than a collection of Linus and Ava Helen Pauling’s prodigious work ethic. Indeed, the archive is so vast and multifaceted that, in a very real sense, it serves as a unique documentation of large swaths of twentieth-century scientific, political and cultural history. By describing so much of the collection on the item-level, researchers are now able to trace lines of inquiry that often have little to do, specifically, with the Paulings’ work.

The successful release of a project of this size is clearly a testament to efficient technical processes. Check back with us next week when we’ll talk a bit more about how Linus Pauling Day-by-Day was created.

Blood and War: The Development of Oxypolygelatin, Part 1

An original container of 5% Oxypolygelatin in normal saline.

“On the basis of the information available to me, I have formed the opinion that oxypolygelatin solution…may well be a thoroughly satisfactory blood substitute, which could be manufactured cheaply in large quantities. It is probably superior to gelatin itself with respect to fluidity of solution, retention in blood stream, and osmotic pressure.”
Linus Pauling, March 14, 1944

In 1941 Linus Pauling began a limited program of study on bovine and human γ-globulin, a project stemming from his interest in the manufacture of antibodies. Pauling initiated experimentation with the preparation of antisera – blood sera containing defensive antibodies – and in the process quickly became an authority on the chemistry of human blood and hemoglobin. Following the Japanese attack on Pearl Harbor and subsequent U.S. entrance into World War II, the federal government issued a national call for research with wartime applications. Thanks to his ongoing immunological work, Pauling was already a step ahead of his fellow scientists.

In April 1942, Pauling submitted a contract proposal to the Committee on Medical Research (CMR) of the Office of Scientific Research and Development (OSRD). Entitled “The Chemical Treatment of Protein Solutions in the Attempt to Find a Substitute for Human Serum for Transfusions,” the proposal outlined a plan to develop a gelatin-based substance which could be used as a plasma substitute. The project, if successful, would produce a synthetic material that would take the place of donated human blood plasma in transfusions, aiding Allied soldiers when America’s peacetime blood reserves ran low.

The Committee on Medical Research accepted Pauling’s proposal and within two weeks Pauling had assembled a group of researchers, including doctors J.B. Koepfli and Dan Campbell, an immunology expert. After securing materials from Edward Cohn and other American-based scientists, the team was ready to begin.

Linus Pauling to A.N. Richards, May 12, 1942

Linus Pauling to Edward Cohn, May 21, 1942, page 1.

Linus Pauling to Edward Cohn, May 21, 1942, page 2.

Pauling’s idea for a plasma substitute was not an unfamiliar one. Gelatin was already in use as a plasma replica during the late 1930s and early 1940s, but its viscosity and tendency to gel at room temperature made it a poor candidate. The U.S. military needed something quick and efficient that could be used in field hospitals with minimal preparation. The Caltech team, however, was not yet ready to discard gelatin as a potential candidate. Pauling hoped that, through chemical processes, he might be able to transform standard commercial-grade gelatin into a workable substance.

Between June 1942 and May 1944, Caltech received approximately $20,000 from the CMR in support of the project. During that time, Pauling and his team were able to successfully develop a possible plasma substitute through the polymerization and oxidation of gelatin.

Notes by Linus Pauling re: the production of oxypolygelatin, July 23, 1943.

This substance, first referred to as polyoxy gelatin and eventually known as Oxypolygelatin, was superior to its unmodified counterpart in several ways. Because it was a liquid at room temperature, Oxypolygelatin did not require the same pre-injection heating that previous substitutes required, allowing it to be used quickly and without the help of heating implements. Furthermore, thanks to the creation of large chain-like molecules during the preparation process, oxypolygelatin was retained in the bloodstream for longer periods, allowing the patient’s body more time to manufacture natural plasma. Finally, where gelatin contained pyrogens (fever-causing substances), Oxypolygelatin did not – a property that was due to the addition of hydrogen peroxide, a substance capable of destroying pyrogens.

To a chemist’s eye, Oxypolygelatin appeared to be an acceptable substitute for human plasma. Unfortunately, Pauling knew his own tests were not enough to convince the CMR of the substance’s viability. What he really needed was a medical expert’s stamp of approval. Pauling called on Dr. Thomas Addis – a kidney expert whom history now credits with curing Pauling’s near-fatal case of glomerular nephritis – to analyze the effects of Oxypolygelatin on human organs. Addis accepted the challenge, bringing fellow researcher Dr. Jean Oliver to the project as well. Over the next two years, Addis and Oliver would subject Oxypolygelatin to a battery of tests, eventually confirming its potential as a plasma substitute.

Despite Pauling’s enthusiasm and Addis’ promising results, the CMR did not believe Oxypolygelatin to be sufficiently superior to the pre-existing gelatin substance and, in the spring of 1944, the committee refused Pauling’s request for a renewal of contract. Surprised by the committee’s decision, he submitted a second request, asking that his contract be renewed for the period of four months, with no additional funding from the OSRD. His request was granted but, due to empty coffers, no progress was made. Pauling applied again in June, this time requesting extra resources for the project. Again, he was denied.

Linus Pauling to A.N. Richards, June 14, 1944.

The future of Oxypolygelatin research looked bleak, but Pauling and his team refused to abandon the project. Instead, they began making preparations for one final assault on the problem.

Please check back on Thursday for the conclusion to this series. In the meantime, for more information on Pauling’s Oxypolygelatin research, read his 1949 project report or view this 1974 letter regarding the development of Oxypolygelatin production in China.  For additional Pauling content, visit Linus Pauling: It’s in the Blood! or the Linus Pauling Online portal.