The OSU Era

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.

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.

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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.

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.

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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. 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

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.

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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.

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.

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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.

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.

[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.

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)

[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.

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.

Formulas, Pictures and Sports Drinks: The Pauling Chalkboard, Part III

Linus Pauling, 1985.

(Part 3 of 3)

While much of the real estate on Linus Pauling’s chalkboard is consumed by lists of names, a number of additional annotations, when examined, prove to be of keen interest.

Metabolic Profiling

On the right side of the board, below the last column of names, is the following text:

NSF – Mol. Str. 21 Mar.

Library 3000 21 Mar.

Aging – NIH Nutrition

American Cancer Society – Dr. Neville

Sample Bank

Mass Spectrometer

Muscular Dystrophy

Aging Patterns in mice

This particular sample of notes relates to the metabolic profiling program carried out for some time at the Linus Pauling Institute of Science and Medicine. As mentioned in part II of this series, a large number of names on the board were involved with the metabolic profiling program, and this particular column of text ties many of the names together. Pauling was working with numerous people from diverse backgrounds and professions. He was in contact with researchers at, among other organizations, the Institute on Aging and the American Cancer Society.

The words “sample bank” refer to urine and blood samples that were to be kept refrigerated for, potentially, decades, and ultimately to be analyzed by mass spectrometry. This particular undertaking was very ambitious, and could have provided a great deal of material for practical study. Unfortunately, the chronically underfunded Institute had trouble with their refrigeration units, and the project was eventually abandoned. (Despite the setbacks, some results of this program of research, headed by Pauling and Arthur Robinson, can be found in articles published at Stanford University as well as in certain of the Institute’s early news releases.)

A New Sports Drink

Another interesting bit of text can be found towards the lower right hand corner of the board:

C + glycine

dextrose

The text is likely the basic outline of a carbonated “sports drink” being worked on by the Institute in the 1980s. The drink was to be infused with vitamins, and the Institute was developing acids that would provide alternative sweeteners. Production and research eventually halted, but it is interesting to think about what may have resulted from a successfully marketed “Paulingaide.”

Vitamin C, Cancer and Heart Disease

The following words, located in the upper right portion of the column ark, have perhaps the most basic and relevant connections to Pauling’s work.

Ascorbate

stimulates

Production of Lymphocytes

The order simply implies that ascorbate, or vitamin C, stimulates the production of lymphocytes, the major cellular components of the body’s immune system. Several studies have shown that increased levels of ascorbate generally correlate with increased levels of lymphocyte production. If nothing else, this is the most centrally relevant theme of Pauling’s work with vitamin C, and the fact that it maintained such a substantial place on his overcrowded board underlines the significance that he himself placed upon it.

In the middle of the board towards its top, is the diagram of a mystery molecule that was crafted by Pauling. Mention of the molecule (given the name “2-azido-5,8-dihydroxy-1,3,4,5,7,9,9b-heptaazaphenalene”) appeared in an article titled “A Prized Collection: Pauling Memorabilia,” published in Chemical and Engineering News in August 2000.

The board's "mystery molecule."

In a 1977 interview, Pauling was asked about his chalkboard and, in particular, about the mystery molecule.  He reponded

I had an idea in the field of organic chemistry about 40 years ago. It involved this unusual compound. Benzine has a six-membered ring of carbon atoms and this compound has three six-membered rings consisting of six carbon atoms and seven nitrogen atoms and then it has these hydroxyl groups attached. It is known that the similar substance with only one ring can be made into certain derivatives that have anti-cancer activity. And I thought that this substance with only three rings might well operate in the same way and that we should study it.

In other words, Pauling was still actively contemplating an idea that had occurred to him 40 years prior – an idea that managed to stay on his chalkboard through his death in 1994. Indeed the mystery molecule exemplifies the function of Pauling’s chalkboard, not only as a mnemonic device, but as a place holder for people and ideas that span decades.

Left of the mystery molecule towards the top of the board, one finds a series of words written one above the other. The seemingly haphazard placement of the words diverts attention from their historical significance in terms of the latter portion of Linus Pauling’s life.

LDL

Cholesterol

Lipoprotein a

The words almost certainly refer to research that Pauling began supporting in conjunction with a German physician named Matthias Rath, which investigated the possibility of a link between vitamin C and heart disease. Over the final years of his life, Pauling spoke of the relationship between vitamin C and heart disease in much the same way that he talked about vitamin C in terms of colds and cancer.

This writing was likely one of the last times that Pauling touched chalk to his board, as his collaboration with Rath did not develop until the early 1990s. The three words both acknowledge and hide the significance of the interaction between Rath and Pauling – a mercurial relationship for much of its duration.

Sandbox

Beneath an ark of name columns, adorned with the mystery molecule at its pinnacle, is a half-circle filled with pictures, figures and chemistry formulas. This area is likely where Pauling exercised the least concern for preservation, and it is supposed that this area of the board was used to aide in his discussions with visitors to his office. The space likely represents over two decades of personal interactions between Pauling and others, a spot on the board where he could explain theories and manifest abstract ideas. In essence, this half circle is where Pauling used the board in a more traditional sense – writing and erasing as suited his needs.

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Linus Pauling’s chalkboard is covered in historical significance. It functioned as an important tool for a very busy man, and has preserved a telling aspect of both the history of the Linus Pauling Institute and the character of Pauling himself, in part reflecting the organization of his consciousness.

 

To be sure, the board is merely a fragment of Linus Pauling and his research, but it is unique and intriguing in a very personal sense. The names, pictures and diagrams on the board all represent important aspects of Pauling’s professional life. Not only does it make a valuable contribution to a room dedicated to the man’s work, it preserves the living memory of Pauling by displaying an intimate demonstration of his method.

Pauling's chalkboard, as preserved in the OSU Libraries Special Collections.