Pauling’s Guggenheim Work During His Battle With Nephritis

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

[Pauling and the Guggenheim Foundation]

In 1941, Linus Pauling’s second year on the Committee of Selection for the John Simon Guggenheim Memorial Foundation, he developed a serious renal disease, glomerulonephritis, that often proved fatal. The onset of this disease emerged during a period of travel that coincided with the Committee’s second meeting of the year, on March 8^th and 9^th. The night before the first meeting, swelling in Pauling’s face became so pronounced that he was forced to acknowledge it during his acceptance speech for the William H. Nichols Medal, granted to him by the New York Section of the American Chemical Society. In his remarks, Pauling joked

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.

Well, 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 other day I said “It is too bad that something doesn’t happen to Senator Wheeler [Anti-interventionist Senator Burton Wheeler] – nothing serious, just something that would lay him up with his eyes shut for two or three weeks” and my wife said “No what you want is something that would keep his mouth shut – his eyes are closed already.”

After speaking with physicians from the Rockefeller Foundation who were able to properly diagnose him, Pauling made plans to see Thomas Addis, a renal disease specialist at Stanford. He did not, however, beg out of the Committee of Selection meetings, though he left immediately afterwards.

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Once Pauling made it back to Pasadena, he was peppered with letters from Guggenheim Foundation Secretary Henry Allen Moe, who wanted Pauling’s input on applicants but, more pressingly, urged Pauling to take care of himself. Following a heavily restricted diet put forth by Dr. Addis, Pauling gradually improved and, by September, reported feeling much better.

Noting this, Moe asked Pauling if he would be interested in traveling to Buenos Aires for six months the following spring to represent the Foundation as a chemist interested in biological questions. Pauling was initially receptive to the idea, writing that it sounded “fun, and perhaps good for me,” but he eventually concluded that he was too busy with war work to seriously entertain the possibility. Though he remained on the Addis diet for quite a long time, Pauling’s most pressing issues with nephritis appeared to be largely behind him. However, five and half years later, Pauling still had to deal with the lingering effects of his poor health.

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Thomas Addis, 1920s

In March 1947, Linus and Ava Helen were busy planning a trip to Oxford University, where Pauling was slated to begin a tenure as George Eastman Visiting Professor. Pauling had also been invited to receive an honorary doctorate from Cambridge that June. Knowing of these forthcoming travels, Addis suggested that Ava Helen take the lead in finding the couple a residence, one outfitted with kitchen suitable to preparing the types of foods that Pauling would need to stay as healthy as possible. The search proved difficult and was compounded by financial issues that Moe and the Foundation eventually helped to ameliorate.

Pauling’s delicate condition also led Addis to suggest that the Paulings travel across the Atlantic by boat rather than plane. But even with three months to go before their planned departure, arranging passage seemed close to impossible. As options began to run out, Pauling asked Moe if he would contact the British ambassador to the U.S., Lord Inverchapel, to see if any room might be available on a government ship. Moe was happy to do so, explaining Pauling’s situation to the diplomat and emphasizing its significance to the two nations’ scholarly relationship. Inverchapel made no promises in his reply, telling Moe that all routes were fully booked, but that he would place Pauling on a waiting list should anything arise. Pauling thanked Moe for trying, but also noted that the situation was less critical now, as Addis had given him the okay to fly and had placed him on a regimen in preparation.

Before he left for Oxford, Pauling got to thinking about Addis’ nephritis treatment and how well it had worked for him. Pauling thought it better than any other treatment then in use and wanted Addis to speak with researchers in England about it. Addis was eager to do so, but hamstrung by a lack of funding. Pauling relayed the details of Addis’ situation with Frank Aydelotte, the Chair of the Foundation’s Committee of Selection, who suggested that Addis could obtain a Guggenheim Fellowship to support his travel. Secretary Moe, on the other hand, did not think Guggenheim funds to be the best avenue of support and recommended that Addis try the Rockefeller Foundation first. If that did not work out, then Moe promised he would reconsider Addis’ case.

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Richard Lippman, circa 1950s

Thomas Addis never received a Guggenheim Fellowship, but after he passed away in 1949, his colleague Richard Lippman did. Lippman had worked on renal disease with Addis for two years at the Stanford University School of Medicine in San Francisco, and had also served in the Medical Reserve Corps during the Second World War. After concluding his stint with Addis, Lippman moved south to the Institute for Medical Research at Cedars of Lebanon Hospital in Los Angeles, where he also became Pauling’s personal physician.

With much support from Pauling, Lippman applied for a 1950 Guggenheim Fellowship to go towards the cost of color plates for a book that he had written and to hire an assistant to help him review Addis’ papers. Pauling found Lippman’s proposals “very important in all their aspects” and they ultimately won generous support, including a $3,600 stipend for one year, $1,500 for working with Addis’ papers, and $1,500 towards the publication of his book. (A $500 Dictaphone was not approved.) Lippman received a renewal the following year, garnering another $3,600 to research renal functions and $1,400 to study Addis’ papers.

In 1960, Pauling himself applied for a Guggenheim Fellowship to support his own work, noting in his application that he had “conquered” his nephritis. Moe was very happy to hear this as he still remembered how Pauling had experienced his first acute episode around the time of the 1941 Committee meeting. In the intervening years, Moe helped navigate some of the logistical consequences of Pauling’s illness and Pauling used his own experience with the disease to put forth quality candidates for Guggenheim Fellowships.

Pauling’s Final Years

Pauling posing at lower campus, Oregon Agricultural College, ca. 1917.

[An examination of the end of Linus Pauling’s life, part 1 of 4]

In 1917, at sixteen years of age, Linus Pauling wrote in his personal diary that he was beginning a personal history. “My children and grandchildren will without doubt hear of the events in my life with the same relish with which I read the scattered fragments written by my granddad,” he considered.

By the time of his death, some seventy-seven years later, Pauling had more than fulfilled this prophecy. After an extraordinarily full life filled with political activism, scientific research, and persistent controversy, Pauling’s achievements were remembered not only by his children, grandchildren and many friends, but also by an untold legion of people whom Pauling himself never met.

Passing away on August 19^th 1994 at the age of 93, Pauling’s name joined those of his wife and other family members at the Oswego Pioneer Cemetery in Oregon. What follows is an account of the final three years of his life.

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Linus Pauling, 1991.

In 1991, Pauling first learned of the cancer that would ultimately take his life. Having experiencing bouts of chronic intestinal pain, Pauling underwent a series of tests at Stanford Hospital that December. The diagnosis that he received was grim: he had cancer of the prostate, and the disease had spread to his rectum.

Between 1991 and 1992, Pauling underwent a series of surgeries, including the excision of a tumor by resection, a bilateral orchiectomy, and subsequent hormone treatments using a nonsteroidal antiandrogen called flutamide. During this time, Pauling also self-treated his illness with megadoses of vitamin C, a protocol that he favored not only for its perceived orthomolecular benefits, but also as a more humane form of treatment than chemotherapy or radiation therapy.

Pauling’s interest in nutrition dated to at least the early 1940s, when he had faced another life-threatening disease, this time a kidney affliction called glomerulonephritis. Absent the aid of contemporary treatments like renal dialysis – which was first put into use in 1943 – Pauling’s survival hinged upon a rigid diet prescribed by Stanford Medical School nephrologist, Dr. Thomas Addis.  At the time a radical approach to the treatment of this disease, Addis’ prescription that Pauling minimize stress on his kidneys by limiting his protein and salt intake, while also increasing the amount of water that he drank, saved Pauling’s life and led to his making a full recovery. Though his famous fascination with vitamin C would not emerge until a couple of decades later, Pauling’s nephritis scare instilled in him a belief that dietary control and optimal nutrition might effectively combat a myriad of diseases. This scientific mantra continued to guide Pauling’s self-treatment of his cancer until nearly the end of his life.

Pauling also believed that using vitamin C as a treatment would, as opposed to chemotherapy, allow him to die with dignity. Were his condition terminal and his outlook essentially hopeless, Pauling felt very strongly that he should be permitted to pass on without “unnecessary suffering.” Pauling’s wife, Ava Helen, had died of cancer in December 1981. She too had refused chemotherapy and other conventional approaches for much of her illness, a time period during which Linus Pauling had helped his wife the only way he knew how: by administering a treatment involving megadoses of vitamin C. This attempt ultimately failed and, by his own admission, Pauling never really recovered from his wife’s passing.

Nonetheless, Pauling continued to lead research efforts to substantiate the value of vitamin C as a preventive for cancer and heart disease in his capacity as chairman of the board of the Linus Pauling Institute of Science and Medicine (LPISM). By the time of his own diagnosis in 1991 however, the Institute was in a desperate financial situation, several hundred thousand dollars in debt and lacking the funds necessary to pay its staff.

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In 1992, while he recovered from his surgeries and managed his illness, Pauling continued to act as chairman of the board of the LPISM. No longer able to live entirely on his own, he split his time between his son Crellin’s home in Portola Valley, California, and his beloved Deer Flat Ranch at Big Sur. When at the ranch, Pauling was cared for in an unofficial capacity by his scientific colleague, Matthias Rath. Pauling was first visited by Rath, a physician, in 1989, having met him years earlier in Germany while on a peace tour. Rath was also interested in vitamin C, and Pauling took him on as a researcher at the Institute. There, the duo collaborated on investigations concerning the influence of lipoproteins and vitamin C on cardiovascular disease.

Not long after Pauling’s cancer diagnosis, a professor at UCLA, Dr. James Enstrom, published epidemiological studies showing that 500 mg doses of vitamin C could extend life by protecting against heart disease and also various cancers. This caused a resurgence of interest in orthomolecular medicine, and it seemed that Pauling and Rath’s vision for the future of the Institute was looking brighter.

As it happened, this bit of good news proved to be too little and too late. LPISM had already begun to disintegrate financially, its staff cut by a third. The Institute’s vice president, Richard Hicks, resigned his position, and Rath, as Pauling’s protégé, was appointed in his place. Following this, the outgoing president of LPISM, Emile Zuckerlandl, was succeeded by Pauling’s eldest son, Linus Pauling Jr. Finally Pauling, his health in decline, announced his retirement as chairman of the board and was named research director, with Steve Lawson appointed as executive officer to assist in the day-to-day management of what remained of the Institute.

One day prior to his retirement as board chairman, Pauling signed a document in which he requested that Rath carry on his “life’s work.” Linus Pauling Jr. and Steve Lawson, however, had become concerned about Rath’s role at the Institute, and particularly on the issue of a patent agreement that Rath had neglected to sign. Adhering to the patent document was a requirement for every employee at the Institute, including Linus Pauling himself. When pressed on the issue, Rath opted to resign his position, and was succeeded as vice president by Stephen Maddox, a fundraiser at LPISM.

After this transition, Pauling met with Linus Jr. to discuss the Institute’s dire straits. Pauling’s youngest son, Crellin, had also became more active with the Institute as his father’s illness progressed, in part because he had been assigned the role of executor of Pauling’s will. Together, Crellin, Linus Jr., and Steve Lawson struggled to identify a path forward for LPISM. Eventually it was decided that associating the Institute with a university, and focusing its research on orthomolecular medicine as a lasting legacy to Pauling’s work, would be the most viable avenue for keeping the Institute alive. The decision to associate the organization with Oregon State University, Pauling’s undergraduate alma mater, had not been made by the time that Pauling passed away.

Pauling 115

This is where we’ll be today.

This coming Sunday will mark the 115th anniversary of Linus Pauling’s birth on February 28, 1901. While we here at Oregon State University are commemorating the birthday anniversary with cake and conversation at the Linus Pauling Science Center, the Pauling Blog observes the occasion in our traditional manner, by looking back at Pauling’s life 100, 75, 50 and 25 years ago.

Lucile, Linus, Belle and Pauline, 1916.

1916

As a junior at Washington High School in Portland, Oregon, Pauling took his first chemistry class in spring 1916.  That fall he began his senior year at Washington and then, in 1917, enrolled at Oregon Agricultural College, at the age of sixteen and lacking a high school diploma. Pauling did not graduate from high school because he neglected to take a required history course, and back then OAC didn’t require high school equivalency for admission.  Linus was always a good student, of course, but during his junior year at Washington he struggled a bit, earning C’s in English and Latin, alongside the expected A’s in solid geometry and chemistry.

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

1941

With the onset of war in Europe, Pauling faced a major personal crisis of his own in 1941. While giving a lecture in New York, Pauling made light of his alarmingly swollen face:

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. Well, 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 other day I said “It is too bad that something doesn’t happen to Senator Wheeler – nothing serious, just something that would lay him up with his eyes shut for two or three weeks” and my wife said “No what you want is something that would keep his mouth shut – his eyes are closed already.”

As it turned out, Pauling’s edema was the result of his having fallen ill with glomerulonephritis, a kidney disease that was usually fatal.  Fortunately for Pauling and for the history of science, he sought out an alternative treatment from Dr. Thomas Addis that saved his life.

Even prior to the Japanese attack on Pearl Harbor, the U.S. was shifting gears in response to the outbreak of World War II. This shift made a direct impact on Pauling’s work at Caltech, and he began putting the brakes on his massive program of research on the structure of proteins in favor of new studies funded by government war contracts, including, in 1941, investigations of elastic explosives and rocket propellants.

Linus Pauling, 1966.

1966

Pauling’s life and work took another dramatic shift in 1966 when he made the acquaintance of Irwin Stone, initially through correspondence.  At a talk on “Science and World Problems” delivered in New York, Pauling had made mention of a desire to live another fifteen years, so that he might be able to witness some of the major advances that he foresaw as being on the close horizon.  Stone was in the audience and sent Pauling a hugely influential letter that detailed a “High Level Ascorbic Acid Regimen” that could “help you achieve this goal and possibly tack on a few extra decades.”  Pauling was intrigued and thus began his famous fascination with vitamin C.

Linus Pauling and a guest in his office at the Linus Pauling Institute of Science and Medicine, 1991.

1991

Now 90 years old, Pauling experienced a difficult year in 1991.  As the year began, the United States was preparing to invade the Persian Gulf, an action that Pauling protested vehemently, taking out a paid advertisement in the New York Times imploring the government to “stop the rush to war.”

Closer to home, Pauling’s friend and close colleague Ewan Cameron, with whom he had published some of his most controversial papers on vitamin C, passed away at the age of 68, a victim of cancer.  That fall, Pauling himself was also diagnosed with prostate and rectal cancer, which he began treating using megadoses of vitamin C and an experimental hormone therapy.  He would live for three more years before passing away on August 19, 1994.

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.