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.


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.

Advertisements

Pauling’s Battle with Glomerulonephritis

[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

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 19301959. 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 19551959. 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.

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:

Peter Pauling, 1931.

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. Developed by Linus Pauling as part of his scientific war work research program, mid-1940s.

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 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 1.

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

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.

the production of oxypolygelatin, July 23, 1943.

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.

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.