Vitamin C and Heart Disease: An Open Question

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A note on LDL cholesterol and Lipoprotein (a) written by Pauling on his office chalkboard.

[An analysis of Linus Pauling’s research on vitamin C and heart disease, part 4 of 4]

In June 1992, Linus Pauling visited the Texas Heart Institute, after which he accepted an offer to write an editorial for the organization’s journal. He completed his short piece, “Can Vitamins Help Control Heart Disease and Strokes?” in March 1993, a little over a year before he passed away.

The Texas Heart Institute article turned out to be Pauling’s final public statement of consequence on the question of ascorbic acid and cardiovascular health. In his text, he argued once again that, although physicians had long known that arterial lesions cause heart disease, they had not yet accepted the evidence that lesions are brought about by low levels of vitamin C in the blood. This consensus had been maintained despite a widely accepted understanding that vitamin C is necessary to repair bodily tissues via collagen production.

Unfortunately for Pauling, the research required to clearly to shift scientific opinion was not forthcoming. Pauling realized that a major study needed to be funded to show a strong relationship between intake of larger doses of nutritional supplements (especially vitamin C) and even greater preventative or therapeutic health benefits for victims of cardiovascular disease. As the idea’s chief proponent, Pauling would have seemed to be a primary figure in attracting grant funds for such a study. However, in part because of the intense controversy over Pauling’s previous work with vitamin C and the common cold, and vitamin C and cancer, Pauling’s reputation had been badly marred within the medical mainstream, and research dollars had become very difficult for Pauling to source.

Partly as a result, his and Matthias Rath’s work stressing the importance of vitamin C as a key factor in combating heart disease was perhaps a case of too little, too late. Though the tandem had succeeded in establishing a general sense of the potential importance of vitamin C in heart disease prevention, the circumstances surrounding their work were not ripe enough for the duo to develop a more complete and lasting understanding of the types and levels of nutrients needed to ensure optimum heart health.


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Linus Pauling giving an interview at Deer Flat Ranch, September 1993.

Other material considerations further compounded the problem. For one, at precisely the same time that the cardiovascular work was gaining traction, the Linus Pauling Institute of Science and Medicine was in the depths of dire financial straits. Furthermore, Linus Pauling was now nearly 93 years old and in declining health. As he battled with the cancer diagnosis that would ultimately claim his life, Pauling realized that could no longer go on assisting Rath. Meanwhile, Rath’s relationship with others in the Institute had fallen into turmoil, and the Linus Pauling Heart Foundation, which Rath directed, was withering on a vine of financial insolvency.

Rath was ultimately asked to leave the Institute amidst a period of legal disarray, partly a result of his having never signed the Institute’s mandatory employee patent agreement. In the wake of his departure from the Institute, and following the death of Linus Pauling in August 1994, the Unified Theory of Human Cardiovascular Disease largely slipped into obscurity, though some echo of it has remained in the public consciousness.


In the years that followed Pauling’s death, the Institute’s cardiovascular program continued to investigate the role that nutrients like vitamin C, E, and B6 might play in limiting oxidative damage brought about by low density lipoproteins (LDL) in individuals suffering from atherosclerosis. Similar work is on-going today in multiple laboratories.

At present, the scientific understanding of the importance of vitamin C in preventing or treating heart disease remains somewhat mixed. Although vitamin C does not appear to directly lower blood cholesterol levels, evidence exists that it does significantly lower low density lipoprotein and Lp (a) levels, which in turn helps to protect arteries from blockage by these cholesterol-carrying molecules.

Total blood cholesterol may also lessen with increased vitamin C intake due to the fact that vitamin C is an HMG-CoA reductase inhibitor, meaning that if vitamin C levels are high, the body manufactures less cholesterol. Additionally, vitamin C’s benefits to the body as both a primary collagen producer and as an antioxidant contribute to what most studies agree to be a significant, though still not fully understood, protective effect against heart disease when taken in doses of 400 to 2,000 mg daily. As in Pauling’s era, this level of supplementation is far above the current Recommended Daily Allowance for adult men and women, which is 60 mg per day.

Likewise, the interaction between lysine and vitamin C that many of Pauling’s case study patients found to be highly therapeutic – with anecdotal reports of actual reversal of atherosclerosis in certain patients – has not been investigated further. And so it is that, more than twenty years after his death, Linus Pauling’s ideas on the impact that nutritional supplementation might make on heart health remain just as tantalizing and out of reach as they were when Pauling was alive and active.

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The Unified Theory of Human Cardiovascular Disease

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[An examination of Pauling’s research on vitamin C and heart disease, part 3 of 4.]

In early 1991, Dr. Howard Bachrach of Southold, New York informed Linus Pauling of experimental results indicating that lipoprotein (a) [commonly abbreviated as Lp(a)] binding to arterial walls could be suppressed through the use of supplemental lysine. In the weeks that followed, Bachrach continued to exchange information with Pauling and his colleague at the Linus Pauling Institute of Medicine, Matthias Rath, in hopes of determining if lysine, vitamin C, or some combination of the two might not only prohibit but actually reverse plaque accretion in vitamin C-deficient guinea pigs.

A breakthrough came about on February 28, 1991 – Linus Pauling’s 90th birthday – when Rath reported to his colleagues his finding that Lp(a), as synthesized in the liver, was in fact regulated in an unknown way by the amount of vitamin C present in the body.

Lp(a) was understood by Rath and Pauling to form from low density lipoprotein (LDL) and Apoliprotein A-1 [abbrevied apo(a)] in the liver in amounts largely determined by the rate of synthesis of apo(a). This rate of synthesis was increased by low vitamin C concentrations in the blood. Rath and Pauling published the finding in Medical Science Research, arguing that plaque formation was not caused by LDL cholesterol, as previously thought, but lipoprotein (a) instead. Crucially, high doses of vitamin C was identified by the authors as being central to reducing these dangerous lipoprotein (a) levels.


This discovery formed the basis for what Pauling and Rath would eventually call their Unified Theory of Human Cardiovascular Disease. Fundamental to this framework was Pauling and Rath’s belief that cardiovascular disease was a degenerative disease caused by vitamin C deficiency. The theory also put forth that humans’ inability to synthesize their own vitamin C drove the disease, though it was also aggravated by genetic defects and exogenous risk factors, such as free radicals introduced by cigarette smoke or oxidatively modified triglyceride-rich lipoproteins exerting a noxious effect on the vascular wall.

Further, lipoprotein (a) was put forth as an evolutionary surrogate for vitamin C in animals – like primates and guinea pigs – that no longer produced their own ascorbic acid. This collection of species shows much higher levels of Lp(a) in the blood, a characterstic seen by Pauling and Rath as serving as an ad hoc biological mechanism used by the body to repair damaged tissues through deposit on weakening arterial walls. Too much Lp(a), however, leads to plaque formation, causing angina, heart attack, and stroke. A lack of vitamin C thus leads indirectly to the deterioration of arteries.

From there, the researchers argued that this problem could be easily fixed if only the recommended doses of vitamin C were increased to levels many times larger than those prescribed by the federal government. Were the body enabled to make use of supplemental vitamin C to produce collagen – as all animals that synthesize vitamin C internally do – humans would be much more efficient at repairing damaged arterial walls. Indeed, vitamin C could function not only to strengthen arterial walls, but also to reduce the amount of Lp(a) being produced by the body and consequently – as a co-factor in the hydroxylation reaction that converts cholesterol to bile acids – lowering the amount of free cholesterol in the blood as well.


vitc-plaque

Published in the Linus Pauling Institute of Science and Medicine Newsletter, March 1992.

To Pauling and Rath, the logic supported their theory was clear. Critics, however, demanded large clinical studies to support the claims, and this was research that the Institute, which was struggling mightily for funds, did not have the resources to pursue.

It was at this point that other interested researchers took up the torch. One of them, Dr. James Enstrom at UCLA, led a 1992 study of over 11,000 human subjects. Enstrom’s work indicated that those individuals who regularly took supplements of vitamin C at federally recommended levels enjoyed significantly lower rates of heart disease than did those not subscribing to a supplementation routine. This data led Enstrom’s team to wonder – in tandem with Pauling and Rath – whether larger doses would achieve an even greater protective effect.

In 1993, hoping to add additional support to the hypothesis, Pauling published three case studies in the Journal of Orthomolecular Medicine. Each study focused on individuals who had suffered from severe cardiovascular disease and undergone surgical procedures, including heart bypass. The individuals in question had read Pauling’s papers with Rath and had decided to try adding lysine and vitamin C to their diet. In certain cases, members of the study group had already been taking fairly high doses of vitamin C and then added lysine.

The 1993 data clearly were not anything like controlled studies and were reported on anecdotally by Pauling. Further, the amounts of lysine and vitamin C ingested varied significantly between individuals, but was generally in the range of between 3 to 6 grams per day of each supplement. Many within the study group reported rapid relief and positive responses.

Though far from authoritative, the published case studies did help to bolster Pauling and Rath’s position, attracting increased interest in the work. However, the duo also received plenty of letters, some filled with irritation, from people who had incorporated supplementation and saw no positive change. Some correspondents, in fact, were getting worse.

Pauling, Rath, and Lipoprotein(a)

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[An examination of Pauling’s research on vitamin C and heart disease. Part 2 of 4.]

In 1989, a young medical doctor by the name of Matthias Rath began working at the Linus Pauling Institute of Science and Medicine. Rath had come from Germany, where he and his colleagues had uncovered evidence that the cause of plaque development in atherosclerosis (the hardening of arteries brought about by cholesterol deposits) was not a direct result of the presence of Low Density Lipoprotein (LDL), as had been previously thought. Rather, the Rath group found that LDL was synthesized in the liver into a new substance called lipoprotein (a), which binds to and carries cholesterol to sites throughout the bloodstream, building up on arterial walls in the process.

In moving to the Pauling Institute, Rath brought with him a specific interest in the potential relationship between vitamin C and lipoprotein(a), or Lp(a). He hoped that, in collaborating with Linus Pauling, he might be able to more fully explain the preventative effects of vitamin C on cardiovascular disease that had been observed in vitamin C-deficient animal models.

However, within the field, there existed significant skepticism as to whether vitamin C could actually affect Lp (a) levels in the blood, since these levels were not known to be modifiable by diet or drugs; – rather, the operating assumption was that the levels were genetically determined. Furthermore, concerns were raised that high doses of vitamin C might lead to an increased zinc-to-copper ratio in the blood, the end result being hypercholesterolemia and a concurrent increase in the risk of stroke or heart attack.

Skeptics also argued that an intense regimen of vitamin supplementation might spur the development of kidney stones, due to the acidification of urine in patients unable to take sodium ascorbate for health reasons. Additional fears were expressed that large doses of vitamin C, vitamin E, and other nutrients that act as blood thinners might interact dangerously with blood-thinning medications taken by many heart patients already.


Unsurprisingly, Rath and Pauling were hopeful that a solution could be found that would put to rest all of the naysaying. In this, the duo was driven by a belief that an optimum amount of vitamin C and other vitamins would mitigate any negative complications while simultaneously preventing a majority of heart disease.

By February 1990, Rath and Pauling were preparing to run experiments using vitamin C-deficient guinea pigs with induced atherosclerosis. These trials, according to Pauling, were devised by Rath and based on the idea that lipoprotein (a) synthesis in a small number of animals might be correlate with the inability to synthesize vitamin C. Pauling remained involved mostly as an eager and interested advisor and patron for Rath’s work on the subject.

In terms of their business arrangement, Pauling made it clear early on that Rath should not be held to the regular patent agreement for LPISM employees (25% royalties to the inventor, 75% to the Institute). Since Rath had developed the idea and foundational work outside LPISM, Pauling suggested a 50/50 split on the profits.

In addition to his scientific work, Rath was also a peace activist, an outspoken opponent of international corporate exploitation, and an advocate for the control of nuclear weapons, and as such he had followed Pauling’s political exploits with great personal interest for many years. Perhaps because of these shared qualities and the growing connection between the two, Rath refused the favorable 50/50 deal that Pauling had recommended. Instead, Rath communicated to Pauling that he believed the Institute should receive any and all profits, leaving Pauling to infer that Rath required no royalties for what he viewed, in principle, as an effort to decrease the amount of suffering endured by people with heart disease. In the end, Rath never signed the Institute’s patent agreement at all.


The first major paper to emerge out of Rath and Pauling’s collaboration was published in Proceedings of the National Academy of Science in December 1990 and titled “Immunological Evidence for the Accumulation of Lipoprotein(a) in the Atherosclerotic Lesion of the Hypoascorbemic Guinea Pig.” The publication reported on Rath’s study and showed that vitamin C protected arteries from fatty build-up at an intake of what would be about 5 grams a day in humans, as adjusted for weight. This dose stood in stark contrast to the much smaller Recommended Daily Allowance at that time, which was 50 mg.

With this paper, it appeared that Pauling had finally acquired a critical piece of evidence that he had been searching for ever since writing Vitamin C and the Common Cold in 1970: experimental proof that a widespread lack of vitamin C in the human diet was resulting in negative health consequences that ranged far beyond scurvy. Likewise, for Pauling, the Rath studies were a clear indication that the federally recommended dose, though sufficient to prevent scurvy, was by no means optimal. Rather, at 50 mg per day, humans were living in a state of chronic vitamin C deprivation and were suffering from a wide range of maladies as a result.


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From 1990 on, the connection between vitamin C and heart disease took center stage in Pauling’s life. Invigorated, he and Rath both saw the topic as a key new focus for research at the Institute, and a program that would pair well with growing national interest in orthomolecular medicine and in controlling health through diet.

To promote this vision, The Linus Pauling Heart Foundation was established as a non-profit agency that aimed specifically to raise money to support the clinical trials needed to determine the exact value of different doses of vitamins needed to prevent cardiovascular disease. In addition to the vitamin C work, the Foundation also sought to  generate funds that would support investigations into alternative heart therapies that used proline, lysine, and niacin.

Once it was established, Pauling named Rath as president of the Foundation, which operated separately from the Institute, but with some financial backing. To draw support for the Foundation’s work, Pauling made regular appearances on media outlets in the San Francisco Bay Area. Likewise, over the course of the next two years, he issued a steady stream of press releases arguing in favor of the use of vitamin C, vitamin B3, nicotinic acid, and lysine to prevent and even reverse the onset of cardiovascular disease. In these, Pauling also alluded to the notion that Lp(a) might be implicated not only in heart disease, but also in diabetes and cancer. No specific optimal vitamin intake was ever detailed in the news releases. Instead, readers were encouraged to make donations to the Foundation so that research to better understand the role that vitamins play in controlling heart disease might more rapidly progress.

Pauling’s Final Years

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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 19th 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.

The End of One Era and the Beginning of Another

Welcome message from then OSU President Paul Risser, 1996.

Welcome message from then OSU President Paul Risser, 1996.

[A history of the Linus Pauling Institute of Science and Medicine, Part 6 of 8]

The beginning of the 1990s proved to be a typically chaotic time for the Linus Pauling Institute of Science and Medicine. Those early years saw the spectacularly fast rise and fall of the collaboration between Matthias Rath and Linus Pauling, ever increasing levels of debt and, in the nick of time, a major bequest which quite possibly saved the Institute from financial oblivion. As tumultuous as the situation had been, it was about to become more so.

In 1993 Steve Lawson’s title was changed from Executive Officer to Chief Executive Officer, though his duties effectively remained the same. At the request of Pauling, one of Lawson’s first actions as was to legally dissolve the Linus Pauling Heart Foundation. He dismissed all of the Heart Foundation’s employees and transferred the entity’s assets to LPISM. At the same time, the Palo Alto zoning law changes of which the Institute had been warned went through – the Institute finally needed to devise a solid idea of where they were going to move.

In the meantime, Lawson, looking to alleviate LPISM’s perpetual financial problems, began negotiating with the Elizabeth Arden beauty company on a deal that he hoped would greatly enhance the Institute’s well-being. Arden and its parent company, Unilever, were seeking research support and eventual endorsement from LPISM for an upcoming line of skin care products, which were infused with vitamin C.  Lawson was interested in both the financial and advertising benefit that might come from this deal, as the Institute badly needed to increase its exposure to a younger and wealthier audience.

The conversation was proceeding smoothly until Arden installed a new president, under whose watch the launch of the new products was mismanaged. This person only remained president for a short period, but the damage had been done. As a result, the deal between LPISM and Elizabeth Arden proved dramatically less prosperous than Lawson had originally hoped.

The Arden deal scrapped, the Institute’s administration encountered more bad news when they received notice that Matthias Rath was suing LPISM, alleging interference with his business practices. Following his departure from the Institute, Rath had encountered difficulty finding financial support for his vitamin C work, as some people assumed that he was trying to claim credit for Pauling’s research. One magazine in particular had published an extensive article on Pauling’s interest in vitamin C and cardiovascular disease and hadn’t even mentioned Rath.  LPISM asserted that Pauling had acknowledged Rath’s contributions in his interviews and that the Institute had no control over what various media outlets published. The lawsuit proceeded nonetheless.


The year 1994 got off to a very bad start. Pauling’s health began to deteriorate markedly and he was forced to undergo treatment for his resurgent cancer, which had spread to his liver. At the same time, the lawsuit with Rath began to intensify while Pauling spent more and more time away from the office, choosing instead the tranquility of his ranch at Big Sur. By the summer, Rath’s lawyers were visiting Pauling’s bedside to try and hash out an agreement. For the Institute, most of the year was spent dealing with these two major issues, though it did arrange to host a conference in September.

Finally, on August 19, 1994, Pauling died at his ranch. The institute that he created and which bore his name instantly felt an intense drain on its morale. Lawson recalled employees sobbing in their work spaces and noted that many staffers felt directionless, unsure what would become of LPISM without its namesake. Ironically, the organization’s financial problems were a bit relieved by this turn of events, as a flood of memorial donations soon came in.

From this moment of darkness, the situation pretty quickly started to improve. The Institute went through with the scheduled September conference, titled “The Therapeutic Potential of Biological Antioxidants.” Many people attended – more than were expected – and the audience was thrilled with the content presented, responding very enthusiastically. In turn, more donations and support began to flow into the Institute’s coffers.

Steve Harakeh, Aleksandra Niedzwiecki and Steve Lawson at LPI's September 1994 conference.

Steve Harakeh, Aleksandra Niedzwiecki and Steve Lawson at LPI’s September 1994 conference.

At the same time, the Institute received notification that another estate of consequence – the Finney estate – had been left to LPISM. This new revenue source, combined with the Swadener gift, allowed LPISM to effectively pay off its debts and even establish a small endowment to support moving the Institute. Coincidentally and almost simultaneously, a large number of bequeaths and other donations began pouring in, largely from donors cultivated years before by Richard Hicks.

The financial situation suddenly and vastly improved, Lawson and Linus Pauling Jr. began seriously hunting for a new location for LPISM. They began contacting universities all over the U.S., with decidedly mixed results. Frustrated, the Institute’s board even briefly considered closing down LPISM in favor of establishing a memorial chair at Caltech or Stanford.

However, Oregon State University eventually came forward and requested that LPISM relocate to Corvallis. In stating its case, the university stressed its historical connection with Pauling, as OSU was his alma mater and home to his papers, which were housed in the university library’s Special Collections. OSU’s argument also pointed out that its existing chemistry, health, and biomedical programs perfectly complemented LPISM and its research. Linus Jr. and Lawson agreed, and decided to move the Institute to the heart of the mid-Willamette Valley.

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In retrospect, the death of Pauling and the decision to move to OSU might now be viewed as equivalent to the death and rebirth of the Institute itself. By the mid-1990s, a new home established and its finances in better shape, the Institute’s future looked brighter than it had in quite some time, despite the passing of its beloved founder.

A Tough Start to a New Decade

LPISM staff assembled for a group photo.  To Pauling's right are Emile Zuckerkandl, Ewan Cameron and Richard Hicks.

LPISM staff assembled for a group photo. To Pauling’s right are Emile Zuckerkandl, Ewan Cameron and Richard Hicks. By 1992, none of these three crucial staff members would remain affiliated with the Institute.

[A history of the Linus Pauling Institute of Science and Medicine, Part 5 of 8]

For the Linus Pauling Institute of Science and Medicine, the difficult decade of the 1980s was one plagued by lawsuits, dramatic monetary problems, and the death of Ava Helen Pauling. Yet for all of its struggles, LPISM soldiered on as best as it could.

One who would help define the decade to come, Dr. Matthias Rath, was a charismatic, intelligent, young German physician who had a passion for vitamin C and cardiovascular health. He had met Linus Pauling on numerous occasions, and in 1989 Pauling invited him to join the LPISM staff. Rath was charming and popular with many of his colleagues. However Pauling’s oldest son, Linus Jr. – a long-time Institute board member – took caution, noting in a 2012 interview his concern that Pauling would offer a position of importance to somebody that he felt was very inexperienced.

Two other major events occurred in 1990: Pauling and Zelek Herman developed a new method to analyze clinical trial data, and the National Cancer Institute installed a new president by the name of Samuel Broder. Pauling immediately began corresponding with Broder, and eventually convinced him to reopen the case for vitamin C as a treatment and prevention for cancer. This resulted in an international conference held in Washington D.C. in 1991 and sponsored by the NCI. It was titled “Ascorbic Acid: Biological Functions in Relations to Cancer.” Pauling was the obvious candidate for keynote speaker and he later said of the conference, “It was great! A great affair! Very exciting!”

Participants in the NCI symposium on Vitamin C and Cancer, Bethesda, Maryland, September 1991

Participants in the NCI symposium on Vitamin C and Cancer, Bethesda, Maryland, September 1991

At this same time, Pauling created a new position at LPISM for Rath, who was named the first Director of Cardiovascular Research. With this, Linus Jr. became even more concerned. Increasingly, he began to question his father’s administrative acumen and began taking steps to assume a more active role in the management of Institute, despite the fact that he lived in Hawaii.

Another big change was on the horizon as well. The city of Palo Alto was planning to change their zoning laws in an effort to increase residency, and informed LPISM that they had three years to find a new home. The Institute realized that the time allotted them was insufficient, and they began a campaign to delay the eviction.  Staff set up card tables in front of businesses, disbursing flyers and circulating a petition to keep LPISM where it was.

The positive response that they received from the locals was staggering and gave the Institute some measure of leverage in their conversations with the city. At one point, Steve Lawson was called before the city council, and one member said that she didn’t want to read in the New York Times that Palo Alto had kicked LPISM out of town. Eventually the council informed LPISM that the zoning law changes were still going to go through, but that the Institute would be granted more time to plan and relocate.


On the research front, after almost two years of marketing Pauling’s superconductor domestically with no leads, Rick Hicks decided to look abroad for a buyer. He contacted parties all over Europe and Asia, and one day a man showed up at the office to inquire about superconductor sales. He identified himself as an employee of the Central Intelligence Agency, which had taken an interest as to why LPISM was trying to sell this research internationally, especially in Japan, instead of on the U.S. market.

Hicks was away from the office at the time, but other employees were able to explain how he had tried unsuccessfully to sell it domestically first. Steve Lawson later recalled the experience as having been a jarring one. Unfortunately for LPISM, they also failed to sell the superconductor abroad and, due to an oversight, misplaced the paperwork required to pay the royalty fee needed to maintain the patent, which they lost as a result.

rath

While this was going on, Pauling and Rath published a paper defining vitamin C deficiency as the major cause of cardiovascular disease. It immediately caused controversy, but the authors stood behind their work and continued on. Once again, concerns about Pauling’s infatuation with vitamin C began to resurge in the scientific community.

Another blow to the Institute’s fortunes was delivered on March 21, 1991, when Ewan Cameron died. His passing rocked the staff and morale plummeted. Shortly afterward, Pauling was diagnosed with prostate cancer and had to undergo surgery. On top of all of this, the fiscal report for the end of 1991 showed that LPISM was hundreds of thousands of dollars in debt. Workers remained loyal however, and numerous employees volunteered to suspend retirement contributions or work at reduced pay to keep the Institute afloat. Despite this, LPISM was still forced to cut their staff in half by early 1992.

Meanwhile, Pauling and Rath continued to promote vitamin C for cardiovascular disease prevention and treatment, and despite continuing doubts about their individual claims, they began to see more support as the medical community gradually realized that it had been underestimating the value of vitamin C for decades. As their work progressed, Rath’s connection to Pauling continued to grow.


In the spring of 1992, more change was clearly afoot when Emile Zuckerkandl’s contract with LPISM was not renewed. This was a controversial move, as Zuckerkandl was well-liked and respected by the staff. After his departure from LPISM, he founded his own institute, the Institute of Medical Molecular Sciences. He asked the Board of LPISM if he could lease space within LPISM for his new IMMS, a request that was granted.

Additionally, Zuckerkandl invited many of the LPISM staff who had been laid off to join IMMS. When he received news that Zuckerkandl was leaving, Rick Hicks, who by now was the Vice President for Financial Affairs, submitted his resignation as well. He had worked very closely with Zuckerkandl and wanted to follow him to other business ventures. The Board was surprised by Hicks’ resignation and the Institute didn’t want to lose its affiliation with him completely, so they elected him to the Board to keep him at least tangentially involved in LPISM. Happily, Hicks’ last act as an employee was to inform the Board that the estate of Carl L. Swadener had been bequeathed to the Institute and that it was valued at $2-3 million.

Linus Pauling Jr. was elected as the next Institute President, replacing Zuckerkandl. The organization that he took over was in grim shape, despite the windfall from the Swadener estate. As he assumed his new office, one of his top priorities was Matthias Rath. Amidst the recent shuffle, Linus Pauling had appointed Rath as Hicks’ replacement and at the same time the two had founded the Linus Pauling Heart Foundation, a separate and parallel organization to LPISM designed to focus on the Pauling-Rath cardiovascular disease research. These decisions were a source of concern to the Board and much of the staff, who were unsure if the Heart Foundation would be a competitor to the Institute, an arm of the Institute or a supporting organization to the Institute.

lawson-lpj

Overwhelmed by work, facing a serious illness and feeling his age, Linus Pauling officially retired from his leadership role at LPISM on July 23, 1992. In the wake of this announcement, the Board elected Steve Lawson as Executive Officer of the Institute, named Pauling its Research Director and Linus Pauling Jr. the Chairman of the Board. Linus Jr. immediately assumed a strong leadership role and, working closely with Lawson, aggressively pursued actions to solve the Institute’s numerous problems.

The two quickly decided that attaching LPISM to a university offered the best chance for its survival. At the same time, they realized that LPISM had become bloated and that they needed to pare back on the organization’s non-orthomolecular research, which had largely been created and expanded under Zuckerkandl’s leadership. While Linus Jr. and Lawson both agreed that the research was worthwhile, they also realized that the Institute simply lacked the funds to maintain it. Zuckerkandl had remained close to LPISM, and when almost all of his research programs were cut, he asked the researchers overseeing these programs to resign from LPISM and join IMMS, which many did.

While this was happening, tensions were mounting between Pauling, Linus Jr. and Matthias Rath. Pauling was informed that Rath had created an office for the Heart Foundation that was separate from LPISM, and that he had done so without permission and without even telling Pauling. He criticized Rath aloud for this decision, which only inflamed the situation.  From there, the speed with which the Pauling-Rath relationship soured was dramatic. In July, Rath was spending great amounts of time at Pauling’s home, and they frequently exchanged letters expressing a close friendship. By August they were hardly on speaking terms, and Rath was ultimately expelled from the Institute, asked to resign over a dispute involving intellectual property rights.

For all of the troubles of the 1980s, the ’90s were getting off to a rough start. The roller coaster ride would continue on in the time ahead, containing both the Institute’s darkest hours and its greatest triumphs.

Two More from Pauling and Rath

Linus Pauling, 1991.

Linus Pauling, 1991.

In the early 1990s, Linus Pauling and Matthias Rath drafted two patent documents not related to their lipoprotein(a) research – documents that did not ultimately result in finalized patents. One of these documents described an attempt to use synthetic polypeptides to prevent disease by helping synthesize an optimum level and strength of collagen in the body.

“Polypeptide and Methods of Use,” application drafted July 10, 1991.

A polypeptide is a linear chain of two or more amino acids linked by a covalent bond. Scientists had asserted that synthetic polypeptides would be ineffective because polypeptides are fairly conservative molecules and, as such, trying to recreate them would result in substances with little or no potency. Pauling disagreed with this sentiment completely and utilized synthetics for the purpose of his research because they were fairly easy to manufacture.

Pauling and Rath believed that synthetic polypeptides would remain viable and that arguments against them were based in a fundamental misunderstanding of what makes a polypeptide potent in the first place. A polypeptide chain with an arginine-glycine-aspartic acid (RGD) sequence was, specifically, what the duo was investigating, and the RGD sequence is the piece of the puzzle that many scientists felt would be a source of potency trouble in synthetics.

Pauling and Rath felt that the RGD sequence was not actually important, but that the R and D was important. Specifically, beginning a chain with R (arginine) then ending it with D (aspartic acid) – both highly polarized end peptides – was the key to imbuing a polypeptide with strength and usefulness. In the eyes of the two researchers, if R and D were in the right spots, it did not particularly matter what resided in between them.

Pauling and Rath’s polypeptide treatment was designed to treat diseases that were related to cell migration or cell membrane adhesion. The treatment would cause certain cells more difficulty in penetrating membranes or just migrating in general; so ideally, it would contain diseases such as metastatic cancer. Also, by preventing membrane penetration and adherence, diseases such as infectious viral agents – which rely on doing just that to spread – would be contained as well.


Matthias Rath

Matthias Rath

“Treatment of Pathological States Related to Degeneration of Extracellular Matrix System Treatment,” application declaration drafted November 1, 1991.

The last patent considered by Pauling and Rath was titled “The Treatment of Pathological States Related to Degeneration of the Extracellular Matrix System.” The extracellular matrix (ECM) provides structural support to animal cells, is the defining feature of connective tissues and serves other important duties in the cellular structure. The November patent idea was for, once again, a Vitamin C mixture, this one designed to prevent the deterioration of the ECM, thought to both contribute to and be characteristic of the spread of diseases, specifically metastatic cancer.

In this instance, Pauling and Rath’s research revolved around apoprotein(a) [apo(a)] which, they theorized, acted as a sort of temporary surrogate to Vitamin C. When Vitamin C levels in the bloodstream drop, apo(a) and lipoprotein(a) levels increase. Apo(a), a crucial component of the body’s defense against disease, was seen as acting as “temporary Vitamin C,” which in the short term was beneficial, but after longer periods of time would actually contribute to ECM deterioration and other health issues.

Pauling and Rath worked with Dr. Aleksandra Niedzwiecki and Dr. Jerzy Jurka on this project, and they all concluded that apo(a) helped the body to fight free radicals and other diseases.  This said, the team also felt that apo(a) needed the help of large amounts of Vitamin C to be effective, especially because, as the body became sick or fought off illness, Vitamin C levels in the blood dropped. As such, large doses of Vitamin C were the best course of action to ensure the strength of the ECM and subsequent general health.

Matthias Rath departed from the Linus Pauling Institute of Science and Medicine in 1992 and Dr. Niedzwiecki moved to work with him at his new institute.  Linus Pauling was already fighting his own cancer at that time and ultimately died in August 1994.  As a result of both events, the patent applications initiated in support of the two initiatives described above appear not to have been vigorously pursued.