Remembering Frank Press

Frank Press

Linus Pauling’s colleague and friend, Frank Press, passed away last month on January 29, 2020 in Chapel Hill, North Carolina. Press was 95 and died of complications from a fall. Perhaps most widely known for his work as President Jimmy Carter’s chief science advisor and his twelve years leading the National Academy of Sciences, Press also collaborated with Pauling on multiple fronts, and the two ultimately grew close.

Press was born on December 4, 1924 in Brooklyn, New York. After earning his bachelor’s degree at City College of New York in 1944, Press went on to Columbia University where he earned a master’s (1946) and a Ph.D. (1949) in geophysics. During that time, Press married his high school sweetheart, Billie (nee Kallick), and the couple remained together until Billie’s death of heart failure in 2009.

After a few years teaching at Columbia, Press was offered a professorship at the California Institute of Technology, where he remained until 1965. Press left Pasadena for a position as chair of earth and planetary sciences at the Massachusetts Institute of Technology, and remained at MIT until he was asked to serve as President Carter’s science advisor and director of the Office of Science and Technology Policy.

Not long after Carter was voted out of office, Press was selected to serve as president of the National Academy of Sciences, where he remained until 1993. Following this, he took up a four-year fellowship with the Carnegie Institute as the Cecil and Ida Green senior research fellow in the Department of Terrestrial Magnetism. His fellowship concluded, Press remained on the Carnegie board for another ten years.


Press’ long and fruitful career brought him into contact with Pauling on many occasions. They first met at Caltech, but did not have cause to interact very frequently, owing to their different departmental affiliations and research agendas. The two began to find a bit more common ground through their shared interest in social justice issues concerning the United States and the Soviet Union. Like Pauling, Press pushed for both nations to sign the partial test ban treaty in 1963. Later, Pauling and Press spoke out to protest the USSR’s treatment of scientist and dissident Andrei Sakharov.

Indeed, shared interest in Sakharov seems to have prompted one of their first formal interactions, a 1983 telegram from Pauling informing Press that he had offered a job to their Russian colleague. Even though the offer did not appease the Soviets enough to release Sakharov, the telegram did catch Press’ attention. Perhaps influenced by Pauling’s actions, the National Academy of Sciences, led by Press, formally renounced the Soviet government’s mistreatment of Sakharov, and refused to participate in a joint US-Soviet scientific cooperation in 1984.


An example of the holiday cards that Frank and Billie Press routinely sent to Linus Pauling

Though Press and Pauling were not successful in securing Sakharov’s release, their shared effort on this issue created space for the two to form a friendship. As president of the National Academy of Sciences, Press sent Pauling a card nearly every year of his tenure, and Pauling become close to Billie Press as well. The friendship between the three was such that Billie often included her own note in the annual holiday card, at one point thanking Pauling for his gift of Florence Meiman White’s book, Linus Pauling Scientist and Crusader. When Pauling announced that he had cancer in 1992, the news shocked the Presses, though they were heartened to learn that he had been well enough to celebrate his 91st birthday with sixteen of his closest friends and family.

Pauling was also concerned with the well-being of the Presses, and it was here that friendship and current research intersected. As his work on orthomolecular medicine moved forward, Pauling was increasingly convinced that the Federal Recommended Daily Allowance (RDA) for certain vitamins, such as vitamin C, were far too low. Pauling believed the RDA should be much higher, and that a higher intake of vitamin C could drastically reduce the chance of developing cardiovascular disease, among other maladies.

Pauling was so convinced of this idea that he took pains to let his friends know that they could easily reduce their risk of heart disease by following the simple step of increasing their vitamin C intake. With this concern in mind, Pauling wrote to Press to urge him and Billie to have blood samples drawn so that their physician might determine the levels of lipoprotein (a) in their systems. Pauling specified that if either of their results came back elevated, “I strongly recommend that you begin a prophylactic regimen, that of taking some extra vitamin C and also perhaps 2 grams per day of L-lysin,” the latter because “the L-lysine interferes with the deposition of lipoprotein in the vascular wall.”

Pauling was also quite willing to review their results. “If the level is high,” he wrote, “there are orthomolecular measures that you should take. Let me know the results of the analyses, and I shall tell you what you ought to do.” Anticipating that the Presses might be nervous about vitamin C megadosing, Pauling wrote that a recent friend of his had used orthomolecular treatments to make a remarkable recovery after being bed-ridden following a third triple by-pass surgery. He signed the letter “Love From,” Linus Pauling.

From the correspondence, it appears as though Press trusted Pauling’s guidance. Shortly after receiving Pauling’s letter, Press replied that he would get his lipoprotein levels checked, and that he and his wife “appreciate[d] [his] interest in [their] well-being.” Press concluded the letter by noting the extent to which he and his wife “have admired you over the years.”


Several months later, in June 1992, Pauling asked Press for his help with an issue of mutual concern. Pauling’s request was spurred by an article that he had recently read titled “Reducing the Risk of Chronic Disease,” a summary of the National Research Council’s landmark, three-year study, “Diet and Health.” The aim of the study was to assist the public in making sound decisions related to their diet. (For one, the notion of “food groups” emerged from this study.)

Pauling called many of the study’s conclusions into question and, not surprisingly, took particular offense to a passage that read, “If you take a dietary supplement, do not exceed the U.S. Recommended Daily Allowance.” Because the statement was coming directly from the National Academy of Sciences, Pauling thought that he might be able to enlist Press’ support in revising its language. In his letter, Pauling was clear in his intent, writing that

I believe that this is an important matter – important to the health of nearly all Americans and other people. It seems clear to me that the members of the Food and Nutrition Board are biased against the optimum use of vitamins and are unwilling to consider the evidence. It is my duty as a member of the Academy to try and rectify this situation.

Pauling’s pleas did not fall on deaf ears. Shortly after receiving his letter, Press replied that he would pass Pauling’s concerns on to the Food and Nutrition Board (FNB) for their “thoughtful consideration” at their next meeting. Pauling’s timing could not have been better, Press explained, because the FNB had recently approved a study to look into nutrition requirements for older adults. As Press noted, this was partially due to Pauling’s inquiries into the “possible roles that antioxidant nutrients may play in preventing acute infections and chronic diseases.” Pauling passed away before the FNB had issued a verdict, but he surely took some degree of comfort at having been heard by his colleague and friend, Frank Press.

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 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.

The Unified Theory of Human Cardiovascular Disease

vitc-stroke-pamphlet

[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.


pauling-heart-foundation

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.

Vitamin C and Cardiovascular Disease: The Roots of Controversy

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Caricature of Linus Pauling created by Eleanor Mill and published in the Philadelphia Inquirer, May 1992.

[Part 1 of 4]

“People are not dying from too much fatty food, they’re dying from too little vitamin C.”

-Linus Pauling, Vitamin C and Heart Disease, 1977

Health-conscious readers of a certain age have likely experienced a frustrating back and forth in food trends over the past several decades, and especially in the 1980s and 1990s. First eggs were said to be bad for you because they are high in cholesterol, then it was learned that they didn’t increase cholesterol in the blood. Likewise, butter was believed to be a health risk because of its high levels of saturated fats, however, butter (especially from grass fed animals, and especially as opposed to margarine) is now argued to be a valuable source of vitamins, minerals, and fatty acids. Chocolate and red meat, too, were decried for being too fatty or, in the case of chocolate, also too sugary. Yet today, both are viewed as useful and even valuable sources of nutrition, so long as they are consumed in moderation.

These swings in consensus swept across the United States beginning in the 1970s largely in response to rising concerns over cardiovascular disease, or CVD. CVD includes a range of maladies such as angina, or heart attack, and many occur in conjunction with atherosclerosis, or the build-up of fatty plaques on arterial walls.

Today, CVD remains the leading cause of death in the United States, claiming over 600,000 lives every year. As health professionals have sought to provide guidance on balanced eating, ideas have flip-flopped on the potential dangers of many foods because, over time, it has become increasingly clear that cutting these foods out of one’s diet altogether had little to no impact on rates of CVD.

Linus Pauling was arguing in support of this point of view long before the data had been gathered to confirm it. Pauling believed that the trend toward removing eggs, red meat, and whole milk from American diets was an ill-advised scheme that restricted valuable sources of protein and nutrients from individuals who often could not afford substitutes for these staple foods. In Pauling’s view, it should have been clear to physicians and other health professionals that these dietary sources of cholesterol could not significantly impact total cholesterol levels in the blood, because cholesterol is synthesized, to a great extent, within the body due to its importance in the maintenance of cell membranes.

The real problem behind heart disease, then, was not a high-cholesterol diet. The problem behind heart disease, Pauling argued, was a widespread failure to ingest a substance that could limit the body’s natural production of life-threatening cholesterol: Vitamin C.


As early as the late 1950s and early 1960s, researchers were uncovering evidence that high vitamin C intake reduced cholesterol in vitamin C-deficient guinea pigs, rats, and rabbits. Perhaps most notably, in the 1950s a Canadian group of researchers led by Dr. G.C. Willis found that above-average cholesterol intake did not result in plaque deposits in non-human subjects’ arteries so long as the diet was paired with a high-dose vitamin C regimen.

Intrigued, Linus Pauling began a search for other champions of this view, and in 1972 he wrote to Dr. Donald Harrison at the Stanford Medical School of Cardiology inquiring into additional research that was being conducted on the interplay between vitamin C and a reduction in the risk of cardiovascular disease. Harrison responded that, although the results were not yet published, he had found lower levels of cholesterol in the livers of guinea pigs that had been fed non-trivial doses of vitamin C.

By 1976 many had come to accept that vitamin C played some role in the regulation of cholesterol metabolism and thus in the progression, or lack thereof, of atherosclerosis and CVD. In addition to Harrison’s studies at Stanford, preliminary work conducted by researchers at Pennsylvania State University found that ascorbic acid and ascorbic acid sulfate (two forms of vitamin C) significantly reduced atherosclerosis caused by cholesterol plaques in rabbits.

However, at about this time, other research projects had suggested the opposite, and indicated that increased intake of vitamin C might in fact increase the risk of heart disease by inhibiting the absorption of copper in the intestinal tract. As a result of this inhibited absorption, the ratio of zinc to copper in the blood would stray from what is ideal and ultimately result in hypercholesterolemia: an imbalance in zinc and copper metabolism that is implicated in coronary heart disease.

These findings created a scenario in which the Pauling camp was squared off against many physicians over the confusing and opposing views that large doses of vitamin C both reduced and increased one’s risk of cardiovascular disease.


Throughout the 1970s, Pauling’s broad argument in favor of the fundamental importance of vitamin C to optimum human health was based on the idea that when primates lost the gene for vitamin C synthesis about forty million years ago, systematic physiological imbalances arose that continue to carry negative health consequences for humans today.

Pauling was quick to point out that all animals require vitamin C to live and that most synthesize it naturally. Yet humans – primates who do not synthesize their vitamin C naturally – typically obtain far less of it in their diet (when adjusted for body weight) than do other primates and non-synthesizing animals like guinea pigs. In addition, animals of this sort, when fed moderate to low levels of vitamin C, showed increased risk for development of arterial plaques of cholesterol.

What was less clear was whether or not this same effect was occurring in humans. Physicians opposed to Pauling’s view based their arguments on the idea that humans are physiologically different in important ways from the animals used to model the effects of vitamin C deficiency in the laboratory. Pauling scoffed at this notion and firmly believed that vitamin C deficiency in humans was the true cause of CVD. But even he could not fully explain exactly why vitamin C should be directly related to heart disease.

Over a decade later, in 1989, when a scientist named Matthias Rath came to the Linus Pauling Institute of Science and Medicine, Pauling would finally find what he believed to be the key to explaining how and why vitamin C was so important to the well-being of the human heart.

The OSU Era

LPI Director Balz Frei, 2010.

LPI Director Balz Frei, 2010.

[A history of the Linus Pauling Institute of Science and Medicine, Part 7 of 8

Despite Linus Pauling’s death in August 1994, prospects were finally beginning to look up for the Linus Pauling Institute of Science and Medicine. By early 1995, finances had improved and, crucially, LPISM had decided to move from Palo Alto, California, to the campus of Oregon State University in Corvallis, Oregon.

Even though the reorganization of the Institute after Emile Zuckerkandl’s departure had shrunk its staff from 75 to 50, it was still determined that LPISM was too big to move to Oregon in its then-current size. For one, many of its development obligations would no longer need to be assumed by Institute staffers, as the OSU Foundation had agreed to lead fundraising efforts, and other staffing redundancies were quickly becoming apparent.

CEO Steve Lawson began to meet regularly with OSU’s Dean of Research, Dick Scanlan, the two carefully studying their staff lists, deciding who and what was most likely to succeed at OSU. Eventually it was agreed that LPISM would move to OSU with a skeleton holdover staff of five people: Steve Lawson, Conor MacEvilly (biochemist), Vadim Ivanov (cardiovascular disease researcher), Svetlana Ivanova (Ivanov’s wife and research partner), and Waheed Roomi (researcher focusing on the cytotoxic molaity of vitamin C derivatives) would come to Oregon.

LPI Staff and faculty affiliate investigators, ca. 1996. Left to right: (back row) Waheed Roomi, Barbara McVicar, Stephen Lawson, Donald Reed, George Bailey, Vadim Ivanov, Ober Tyus; (front row) Svetlana Ivanova, Rosemary Wander, Peter Cheeke, Conor MacEvilly; (not pictured) David Williams, Philip Whanger.

LPI Staff and faculty affiliate investigators, ca. 1996. Left to right: (back row) Waheed Roomi, Barbara McVicar, Stephen Lawson, Donald Reed, George Bailey, Vadim Ivanov, Ober Tyus; (front row) Svetlana Ivanova, Rosemary Wander, Peter Cheeke, Conor MacEvilly; (not pictured) David Williams, Philip Whanger.

In preparing for the move, Lawson worked closely with Scanlan and OSU president Dr. John Byrne to hammer out the specifics of how to integrate LPISM into OSU. In 1995 Linus Pauling Jr., Lawson, and incoming OSU president Paul Risser all signed a Memorandum of Understanding that laid out how everything would be transferred to OSU, and how LPISM would be legally dissolved as a separate entity. OSU promised to provide the Institute with administrative and laboratory space on the fifth floor of Weniger Hall, which had just been renovated. The university also pledged additional funding for salary lines, and to work toward eventually housing LPISM in its own building should it someday outgrow Weniger Hall.

The big move was made in July 1996. LPISM was able to bring with it an endowment of $1.5 million, which the state of Oregon agreed to match. As they moved, the remaining staffers purged much of their material: Lawson estimated that they filled two full-sized dumpsters per week immediately before, during, and after the move.

Upon arrival, the Linus Pauling Institute was created as a separate entity from LPISM, which continued to exist as a shell company for several years afterward. LPISM needed to continue to live as many bequests had been specifically made out to LPISM, and there was the issue of standing lawsuits from Matthias Rath and another former staffer who was suing LPISM for wrongful termination. Due to these legal reasons, and despite the fact that, by 1996, it had ceased to exist on anything but paper, LPISM was not finally dissolved until the mid-2000s.


Maret Traber, one of the world's leading experts on vitamin E.

Maret Traber, one of the world’s leading experts on vitamin E.

Once settled in Corvallis, the Institute’s fortunes continued to improve. For one, the financial problems which had plagued the Institute for all of its life basically vanished. Regular influxes of donations coupled with residence at OSU saved a fortune for LPI, which no longer had to pay rent or keep a fundraising staff on its payroll.

Next, after a long and thorough search, Balz Frei was hired as director of LPI in the summer of 1997, a position that he holds to this day. The Institute spent the rest of the late 1990s setting up its research agenda and recruiting new faculty. In 1998 LPI hired Tory Hagen, Maret Traber, and Rod Dashwood, all acclaimed scientists whom Lawson described as the “research backbone of the Institute.” (presently all three hold endowed professorships) Shortly afterward David Williams was hired from within OSU as another principal investigator; he ended up holding numerous positions at LPI and was very important to its success in the following years.

In 2000 LPI launched one of its most successful projects: the Micronutrient Information Center, which has proven to be a highly popular and dynamic outreach program. The resource, which continues to expand, provides information on dietary intake and encouragement for healthy living. While it still advises vitamin C doses much higher than that recommended by the FDA, the numbers involved are far from Pauling’s recommended megadoses of the 1970s and ’80s.

lpi-conference-2003

The year 2001 was another big one for the Institute, in part because of their hosting the first Diet and Optimum Health Conference that winter. As part of the conference, they presented the first Linus Pauling Institute Prize for Health Research to Dr. Bruce Ames, along with a $50,000 award. In the span of a decade, the Institute had gone from being hundreds of thousands of dollars in debt to being able to award a biennial prize of $50,000 – tangible evidence of a truly remarkable turnaround. That year LPI also hired Joe Beckman, who opened up a new area of research for LPI through his focus on amyotrophic lateral sclerosis, or Lou Gehrig’s disease.

The ensuing decade was refreshingly free of drama – certainly so by past LPISM standards – and saw unprecedented growth. In 2002 the general expansion of LPI’s research support staff continued and in 2003 the second Diet and Optimum Health Conference was held with the signature prize going to Dr. Walter Willett of Harvard University. The third, fourth, and fifth conferences were held in 2005, 2007, and 2009 with Drs. Paul Talalay, Mark Levine, and Michael Holick winning the awards at each event.  In 2011 the prize went to OSU alum Dr. Connie Weaver; this year the biennial conference is scheduled to take place in May, and another LPI Prize will be announced then.


Jane Higdon.

Jane Higdon, 1958-2006.

In an otherwise near-spotless decade of growth and good news, one tragic occurrence did befall the Linus Pauling Institute. On May 31, 2006, Jane Higdon, a prolific writer, well-known researcher, creator of the Micronutrient Information Center, and six-year veteran of LPI, was hit and killed by a logging truck while bicycling near her home in Eugene. In her honor, the Jane Higdon Foundation was established, the trucking company involved in the accident donated $1 million to bicycle safety programs, and LPI set up the Jane V. Higdon Memorial Fund. The Higdon Foundation’s goal is to create “scholarships and grants to encourage and empower girls and young women to pursue healthy and active lifestyles and academic excellence” and also to promote bicycle safety in Oregon’s Lane County. The Memorial Fund is largely dedicated to supporting the Micronutrient Information Center.

Buoyed by the success of its past outreach efforts, LPI decided to expand its education programs to include young people as well, launching the Healthy Youth Program in 2009. The Program is aimed at elementary- and middle school-age students, and promotes healthy lifestyles and nutrition.

At the same time, LPI responded to the “Physicians’ Health Study II on Vitamin C and E and the Risk for Heart Disease and Cancer.” Published in the Journal of the American Medical Association, the study claimed that vitamins C and E were useless in treating cardiovascular disease. LPI retorted that the research directly contradicted numerous other contemporary studies, that it failed to accurately measure vitamins in the bloodstream, and that a ten-year study isn’t adequate time to gauge the effect of vitamins on cardiovascular disease.  LPI’s public response was emblematic of its participation in public debate; presently the Institute is looked upon as a respected and valuable contributor to many conversations concerning, as Linus Pauling would have put it, “how to live longer and feel better.”

For the first time in its existence, things were going very smoothly for LPI. As the first decade of the new millennium came to a close, the future looked even brighter, a welcome change from the past.  Exciting news was not long at hand.

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.

Lipoprotein(a) Patents

Promotional literature for the Linus Pauling Heart Foundation, ca. 1992.

Promotional literature for the Linus Pauling Heart Foundation, ca. 1992.

[Part 2 of 2]

With the results of their Lipoprotein(a) [LP(a)] experiments in hand, Linus Pauling and Matthias Rath decided to create a treatment and try to patent it. Their treatment relied on three main ideas: First, that increased Vitamin C levels in the bloodstream would prevent the creation of lesions to which Lp(a) might bind. Second, that lipoprotein binding inhibitors would detach any plaque that had already built up. And lastly, that Vitamin C would then also help the body to filter out Lp(a). In this way, it could be used to both treat and prevent cardiovascular disease (CVD) and other related cardiovascular problems.

The duo also saw great potential use for their research in surgery – specifically angiopathy, bypass surgery, organ transplantation, and hemodialysis. Lysine or other similar chemicals naturally help to speed the healing process and also act as blood clotting agents, therefore reducing the risk of blood loss during surgery. Also, patients undergoing organ transplant surgery, bypass surgery, and hemodialysis often suffer strong recurrences of CVD, which Pauling and Rath felt was due to depleted Vitamin C levels from blood loss. Similarly, diabetics often suffer from both inhibited Vitamin C absorption and higher levels of Lp(a), leading Pauling and Rath to hope that their work could help to treat diabetes-related CVD as well.

When living patients were using their treatment, the mixture was designed to be taken orally in pill or liquid form, or injected intravenously. Pauling also wondered if the mixture could be taken subcutaneously (injected into the deepest level of skin), percutaneously (injected into internal organs), or intramuscularly (injected into the muscle). When being used as preparation for transplant surgery, the organs to be transplanted were to be soaked in the mixture. Later research done by other scientists showed that Vitamin C is not absorbed into the bloodstream like it was thought, and that there are specific Vitamin C carrier molecules in the digestive tract, therefore limiting the amount of Vitamin C a person can absorb when taken orally. As such, injection is a much more effective method of getting Vitamin C into the bloodstream.

Pauling and Rath’s work was polarizing, if not unprecedented. As far back as the early 1970s, enthusiastic support for Vitamin C by Pauling and others had been a point of extreme controversy. Now, even with this latest batch of research, many scientists and doctors seemed to think that their conclusions were grossly incorrect, and in some cases even dangerous for people. Pauling, Rath, and their supporters felt that the harsh criticism emerged, at least in part, from pharmaceutical companies concerned about losing revenue if people stopped buying their expensive medications and instead bought inexpensive, common Vitamin C. On the flip side, many of the people who felt that their research was correct were absolutely steadfast in their support.

The controversy surprised Pauling. He repeatedly expressed these feelings, pointing out that he was not the first to make claims about the benefits of Vitamin C nor even the most extreme, and yet he was viewed as a controversial figure espousing fringe medicine. The Pauling-Rath team was not the only organization researching and promoting the positive effects of Vitamin C. Other groups, such as that led by Dr. Valentin Fuster of Harvard Medical School, were conducting similar experiments. Pauling and Rath attempted to collaborate with them where possible, often with success. But more generally the duo had to rely heavily upon individual case histories to support their research, largely because they were unable to convince major American institutions to conduct their own studies or to sponsor the Linus Pauling Institute of Science and Medicine’s studies.

Figure 1 from Pauling and Rath's July 1990 patent application.

Figure 1 from Pauling and Rath’s July 1990 patent application.

On July 27, 1993, Pauling and Rath were awarded a patent for the application filed in April 1990. On January 11, 1994, they received a second patent for the application filed in July 1990. Shortly afterward, in March 1994, the two filed a third application, following similar grounds, titled “Therapeutic Lysine Salt Composition and Method of Use.” The compound they were patenting was a mixture of ascorbate, nicotinic acid (also known as Vitamin B3 or niacin) and lysine, or a lysine derivative. The mixture was to be combined at a ratio of 4:1:1, and include a minimum of 400 mg of ascorbate, 100 mg niacin and 100 mg lysine. The mixture functioned more or less identically to the previous two patents, the major difference being the inclusion of Vitamin B3 for its antioxidant properties. Pauling and Rath also encouraged the inclusion of additional antioxidant vitamins.

This was the last patent that Pauling and Rath would file together. Shortly afterward the two experienced a falling out and Rath left LPISM.  A few months later, on August 19, 1994, Linus Pauling passed away from cancer.

The third patent application was approved and awarded to Pauling and Rath in 1997. The two hadn’t made any profit off of the previous patents to speak of, and research that followed in the later 1990s and after 2000 showed that Vitamin C appeared to have no real effect on Lp(a). The discrepancy between the Pauling-Rath trials and subsequent tests seem to be attributable to the major differences between the two test subjects – humans and guinea pigs. However, other trials have shown that large doses of Vitamin C are useful in fighting cardiovascular disease – for reasons other than Lp(a) levels – and also work to combat stroke, decrease blood pressure and provide other health benefits.

Additional studies in the wake of Pauling and Rath have also revealed the complexity of Lp(a).  The compound is today regarded to be somewhat of a mystery in terms of function, as scientists aren’t very clear on what it does in the human body. Also, “normal” levels of Lp(a) vary massively on an individual basis, a trait that seems to trend along racial lines. As a result, choosing Lp(a) as a target for medication has proven to be extremely difficult.

Experimenting with Lipoprotein(a)

lpa

[Part 1 of 2]

In the late 1980s into early 1990, Linus Pauling and a colleague, Matthias Rath, worked intensively on the health benefits of Vitamin C and Lipoprotein(a) binding inhibitors. In 1990 they applied for two patents related to that research. The first, applied for in April, was titled “Use of ascorbate and tranexamic acid solution for organ and blood vessel treatment prior to transplantation.” The second, submitted in July, was titled “Prevention and treatment of occlusive cardiovascular disease with ascorbate and substances that inhibit the binding of lipoprotein (A).”

The technique that Pauling and Rath were attempting to patent in April was both a method and a pharmaceutical agent designed to prevent and treat fatty plaque buildup in arteries and organs and also prevent blood loss during surgery by introducing into a patient (or organ) a mixture of ascorbate and lipoprotein(a) [Lp(a)] binding inhibitors, such as tranexamic acid.

Tranexamic acid is a synthetic version of Lysine, and ascorbate is the shortened name for L-ascorbic acid, or more commonly, Vitamin C. Lp(a) is a biochemical compound of lipids and proteins which binds to fibrin and fibrogen in the walls of arteries and other organs, which causes plaque buildup, which in turn often results in atherosclerosis – the thickening and embrittling of arterial walls – and cardiovascular disease (CVD), one of the most common causes of death in the United States. The second patent described effectively the same method, but focused more on CVD and less on surgery.

Pauling and Rath noticed that humans and a select few other animals are the only creatures that suffer from heart attacks and other issues associated with the buildup of plaque in the circulatory system. One common link between all of these creatures is the fact that they do not naturally produce Vitamin C, and therefore must obtain it solely through diet. The duo hypothesized that the cause of Lp(a) buildup was due to a lack of Vitamin C, and that if Vitamin C intake was increased, it would help the body filter out Lp(a) and therefore decrease the amount of Lp(a) in the bloodstream. They decided to run tests on Hartley guinea pigs, since they are one of the few other animals that don’t synthesize their own Vitamin C.

rath

The first test was run on three female guinea pigs, each about a year old and weighing 800 grams. The animals were all fed a diet devoid of ascorbate (e.g., a hypoascorbate diet), and given an injection daily of ascorbate so that Pauling and Rath could easily monitor and control their intake. The first pig was given ascorbate at a ratio equivalent to 1 mg per kilogram of body weight (1 mg/kg BW). The second pig was given 4 mg/kg BW, and the third was given 40 mg/kg BW.

The experiment only lasted three weeks, because Pauling and Rath didn’t want to inflict scurvy upon the guinea pigs. Creatures deprived of Vitamin C for prolonged periods develop scurvy, an incredibly painful condition where the victim becomes lethargic and begins to suffer skin color and texture changes, easy bruising, brittle and painful bones, poor wound healing, neuropathy, fever and eventually death.

The guinea pigs had their blood drawn at the start of the test, then once again after ten days. At the end of three weeks, the animals were anesthetized and euthanized, then dissected. Their results showed that the hypoascorbate guinea pigs had noticeably higher plaque buildup and general amounts of Lp(a) in their bloodstream. Upon closer analysis of the organs and the arterial wall, the researchers discovered that the guinea pigs had also developed lesions along the walls of their arteries, to which Lp(a) was binding even more than normal.

Pauling and Rath then ran a more expansive second test, with a test time of seven weeks and a test group of thirty-three male Hartley guinea pigs, each approximately five months old and weighing 550g. At the outset, the subjects were split into multiple groups. Group A consisted of eight guinea pigs and was given 40 mg/kg BW of ascorbate daily, while Group B consisted of 16 guinea pigs given 2 mg/kg BW daily. At five weeks all of Group A was euthanized and studied, as was half of Group B. The second half of Group B then had their daily dosage increased to 1.3 g/kg BW for two weeks before being euthanized.

Once again, it was observed that the hypoascorbate guinea pigs had developed lesions in their arterial walls and organs, as well as increased plaque buildup and Lp(a) levels. On the same token, the second half of Group B showed decreased levels of Lp(a) in their blood and decreased amounts of plaque after their ascorbate intake was dramatically increased.

Pauling and Rath felt that their research was confirming their hypothesis, and wanted to see how it would function on humans. Their method here was to obtain post-mortem pieces of human arterial wall. They cut the pieces into smaller sections, and for one minute placed a piece weighing 100 mg into a glass potter containing 2.5 ml of a mixture of ascorbate and tranexamic acid. Compared to the other pieces, the portions in the mixture released sizable amount of Lp(a).

This promising data in hand, Pauling and Rath then began to think about patenting and marketing their work.

John Yudkin, Linus Pauling and the Sugar Question

In my book I say you shouldn’t eat sweet desserts, but I also quote a professor who says that this doesn’t mean that if your hostess has made this wonderful dessert you should turn it down.  My wife used to say I always looked for that hostess.

-Linus Pauling, 1987.

Linus Pauling and John Yudkin shared a semisweet bond that was nearly equal parts contradiction, respect and humor, and which lasted from the mid-1970s until Pauling’s death in 1994. The two men held radically different views on a number of topics including the effects of vitamins, especially vitamin C, but shared an identical view on the dangers of sugar. Indeed, Yudkin’s claims in his 1976 book This Nutrition Business that Pauling’s beliefs about vitamin C were completely incorrect did not deter Pauling from citing Yudkin’s work on sugar in a favorable light in How to Live Longer and Feel Better, published ten years later.

John Yudkin was born in London in 1910, earned a degree in chemistry and a Ph. D in biochemistry, and later studied medicine in London. As the Chair of Physiology at London University at Queen Elizabeth College, he persuaded the university to institute a Department of Nutrition in 1954, the first department in Europe devoted to undergraduate and postgraduate teaching and research in nutrition. In 1954 Yudkin became the Chair of Nutrition for Queen Elizabeth College. In the 1960s, he grew increasingly concerned with the role of nutrition in western afflictions like obesity and diabetes, and spoke of the problem of “the malnutrition of affluence.” Yudkin retired from Queen Elizabeth College in 1971, and became Emeritus Professor of Nutrition.

Pauling first commented on Yudkin’s work – chiefly his book Sugar: Sweet and Dangerous – in a 1972 article for the newsletter Executive Health. In it, Pauling summarized Yudkin’s belief that sugar is an important cause of coronary heart disease, and that saturated fat and cholesterol are not. He also described a study carried out by Yudkin in 1957, in which the death rate from coronary disease in fifteen countries was correlated in relation to the average intake of sugar. The study concluded that men consuming relatively large amounts of sucrose faced far greater odds of developing heart disease in the age range of 45 to 65, than did those who did not ingest as much sucrose. Pauling agreed with Yudkin’s findings that sugar not only provided “empty calories,” but also contributed to various diseases.

In 1976 Pauling received a copy of Chapter 12 of Yudkin’s book, This Nutrition Business, in the mail.  In this chapter, titled “What You Can Expect from Vitamins,” Yudkin stated that Pauling’s claims about vitamin C were untrue. Yudkin suggested that the human body needs a certain amount of vitamins and no more, and that to ingest more vitamins than are required is a waste – thinking that was common at the time. He added that he knew Pauling personally and thought of him as warm and friendly, but also that “I think sincerely that he is wrong in most of what he says about vitamin C and about the use in large amounts of this and other vitamins in the preservation of health and in the treatment of disease.”

He then proceeded to find fault in Pauling’s argument that the best diet is one of raw fruits and vegetables; a diet that would provide roughly the same amounts of vitamin C that humans consumed millions of years ago. Yudkin instead argued that humans have subsisted on an omnivorous diet for at least two million years, and that if they really weren’t ingesting enough vitamin C they would have died off long ago.

The year after Yudkin wrote about Pauling in his book, Pauling – in what may have been a retaliation of sorts – singled out Yudkin as an example of subjective reporting on nutrition.  Pauling mailed his editorial “Needed: More Responsibility, More Objectivity, Less Bias,” to Yudkin along with a short note telling him that he was sorry to have to use him as an example, and that he hoped Yudkin would “get around to examining the evidence about nutrition in relation to disease in an unbiased and responsible way sooner or later.” Yudkin answered Pauling with a terse note informing him that his views were simply different, and that Pauling should not accuse people of being biased and irresponsible just because they had differences of opinion.

It was clear by 1986 that all was forgiven, when Pauling cited Yudkin extensively in his book How to Live Longer and Feel Better.  In Chapter 6, Pauling discussed Yudkin’s book Sugar: Sweet and Dangerous, in which Yudkin demonstrated that ingesting sucrose leads to coronary disease. According to Pauling,

Against the general public acceptance of the proposition that coronary heart disease is caused by a high intake of animal fat (saturated fat) and the eating of foods containing cholesterol, Yudkin himself has shown that for some countries the correlation of coronary disease with intake of sugar is much better than that with intake of fat.

Pauling later commented that “It has been shown in a trustworthy clinical study that the ingestion of sucrose leads to an increase in the cholesterol concentration in the blood.” The trustworthy study of which he speaks was reported by Milton Winitz along with his associates in 1964 and 1970. This investigation studied eighteen prisoners who had volunteered to be locked into an institution for about six months and have their cholesterol levels recorded as they were fed a specific diet. After a preliminary period, the group was placed on a small-molecule diet made up of seventeen amino acids, a little fat, vitamins, essential minerals, and glucose.  From there, more sucrose was added back into the diet.  During the length of the study, the group’s cholesterol levels were closely monitored.

The average cholesterol concentration during the initial period, during which the subjects had been fed a standard Western diet, had been 227 milligrams per deciliter. After two weeks on the glucose diet, the average concentration dropped to 173 and, two weeks later, to 160. After that point, a quarter of the glucose in the subjects’ diet was replaced by sucrose. In a week the average cholesterol concentration was 178, and two weeks later it had risen to 208. The glucose was then added back into the diet, replacing the sucrose, and results were evident in one week, when the average cholesterol concentration dropped to 175, and kept dropping afterward to points even lower than the 160 initially recorded. In his book, Pauling stated that this study “shows conclusively that an increased intake of sucrose leads to an increased level of blood cholesterol.”

At the end of Chapter 6, Pauling concurs with Yudkin and gives advice to the reader regarding sugar. His first admonition is to keep away from the sugar bowl – to keep it out of your coffee or tea. He also warns against prepared, frosted breakfast cereals, and to keep away from any regular intake of sweet desserts. His last piece of advice is to avoid soft drinks. In a different section of the book, Pauling advises, as part of a regimen for better health, to “keep your intake of ordinary sugar (sucrose, raw sugar, brown sugar, honey) to 50 pounds per year, which is half the present U.S. average.” (By 2003, Americans were consuming 142 pounds per year, on average.)

In December 1987, Pauling was interviewed for the magazine Outside for an article that focused specifically on his views on sugar. In it, Pauling is quoted as saying, “the increasing incidence of [coronary] disease closely parallels the increasing consumption of sugar. It is not at all correlated with the consumption of animal fat (saturated fat) or of total fat.” With this, Pauling reaffirmed his support for Yudkin’s viewpoint that sucrose is the primary culprit behind cardiovascular disease.

In 1989 Yudkin visited Pauling in person and, shortly thereafter, sent to Pauling a copy of his latest book Pure, White and Deadly. In thanking Yudkin for the book, Pauling asked if he would be willing to serves as a member of the Board of Associates of the Linus Pauling Institute of Science and Medicine. He also asked for a biographical sketch to be run in the Institute’s newsletter, and likewise asked for permission to reprint parts of the book in the publication.

Yudkin eventually agreed to join the Board of Associates (once assured by Pauling that his joining would not involve any work, since he had too much already) and provided a biographical sketch along with a letter in which he joked that he had “excluded such interesting aspects of my life as what clothes I wear, what I have for breakfast…”  Little bits of humor such as these dot the correspondence between the two men, who maintained a friendly relationship despite their occasional public disputes.

In a memo relaying news of Yudkin’s appointment to the Board, Pauling noted that “[i]t was Yudkin’s work that caused me to make my strong recommendations about decreasing the intake of sucrose.” Pauling also obtained copies of Pure, White and Deadly to distribute to members of the Institute, and continued to promote the book in the LPISM newsletter. Clearly, although Yudkin contradicted Pauling’s strong arguments in support of vitamin C, Pauling saw the logic in Yudkin’s case against sugar and stood firmly behind it.