LINUS
PAULINGINSTITUTE
DIGITAL DIGEST

SUMMER/FALL 2023

UPDATES FROM THE MICRONUTRIENT INFORMATION CENTER

LOOK INSIDEA MAN OF LEGEND

Highlights of Dr. Linus Pauling’s Life as Told by Chris Petersen

On April 11, 2023, Chris Petersen from the OSU Libraries presented the webinar
Visions of Linus Pauling: Reflections on the Man and His Institute. This engaging
presentation provided a comprehensive view into the remarkable life of Dr. Linus
Pauling, mirroring Petersen’s latest book, Visions of Linus Pauling.
The article below is a brief synopsis of Petersen’s presentation, touching only on
Pauling’s unwavering commitment to health research and the captivating historyof the Linus Pauling Institute of Science and Medicine.
The full recording of the webinar and interviews with Petersen are available
on our YouTube channel. A condensed transcript of Petersen’s presentation isavailable upon request.

A Pioneer in Chemistry and Molecular Biology
Dr. Linus Pauling was a talented structural chemist. He exhibited a remarkable ability
to visualize the true nature of molecules and formulate hypotheses about molecular
structures from experimental data.
In the first few decades of his career, Pauling meticulously deciphered the structures ofdozens of small molecules using the innovative technique of X-ray crystallography. With
this, he made substantial contributions to the burgeoning field of structural chemistry
and deepened his understanding of atomic interactions.
In the mid-1920s, Pauling went to Europe as a Guggenheim Fellow and learned about
quantum mechanics, a then emerging topic in the field of physics. As a result, Pauling
was able to better understand and describe chemical bonding – that is, the way atoms
join together to form molecules.
Continued on page 4

IN THIS ISSUE
A Man of Legend.....1
From the Director....2
Micronutrient
Information Center
Updates...................3“Come Fly With Me”
Recap......................7

FROM THE DIRECTOR
Greetings from the Linus Pauling
Institute, and welcome to the very firstedition of the LPI Digital Digest!

Our final webinar of 2023 is tentatively
scheduled for early December. I will bepresenting our latest outreach endeavor:
The LPI’s Top Ten – a guide focusedon essential nutrients for addressing
common health concerns with a special
spotlight on older adults.

Photo credit: Karl Maasdam

You’ll notice that the digest bears
a resemblance to our LPI ResearchNewsletter. While the familiar format
remains, the Digital Digest provides
summaries of our online endeavors
and outreach initiatives, rather thanfocusing on our published scientificwork (those studies will continue to behighlighted in the newsletter).
Emily Ho, PhD
Endowed Chair and Director,
Linus Pauling InstituteAs with our previous webinars,
registration is required to watch it live.
We’ll be sure to let you know as soon as
we have it scheduled so you can sign up.

In this inaugural issue, we’re excited
to bring you insights from two of
our recent webinars. Check out
the captivating article on the coverbased on the webinar “Visions ofLinus Pauling: Reflections on the Man
and His Institute” all about Dr. Linus
Pauling and the history of the Institute.
Also, make sure to read our article
on page 7 with a follow-up from thewebinar “Come Fly with Me: New Tools
to Investigate Parkinson’s.”Mark your calendars, as our next editionof the LPI Research Newsletter is set tohit the scene in November, where we’llbring you more in-depth information
about our recent scientific publications.
And one more thing: Don’t miss the
updates from our online Micronutrient
Information Center on the next page.
You can expect to see more from the
MIC in the spring.
Hope you are enjoying the start of fall!

LPI IN THE NEWS•Dr. Emily Ho is the 2023 OSU Alumni Association
Distinguished Professor, as announced during
University Day at Oregon State University.
Dr. Richard van Breemen won the OSU Impact Award
for Outstanding Scholarship at the same event.

•Dr. van Breemen was also named on the 2023 Power
List by The Analytical Scientist for the third year in arow.

•

A research team led by Drs. Fred Stevens and Adrian“Fritz” Gombart found that a compound derived
from hops reduces the abundance of a gut microbe
associated with metabolic syndrome.

•Drs. Tory Hagen and Kathy Magnusson recently
published their latest clinical trial in older men,showing that shows daily multivitamin use improves
nutritional status and helps to maintain cellular
metabolic functions.

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The Linus Pauling Institute’s newest
clinical trial on multivitamins will befeatured in the next issue of the LPI ResearchNewsletter, coming in November 2023.

MICRONUTRIENT INFORMATIONCENTER UPDATES
Choline Article•

New Section on Inadequacy: Most people in the United States fall short of
the recommended daily intake of choline in their diets. Specific segments of the
population face a higher risk of inadequate choline intake. Notably, vegetarians
and vegans, as well as pregnant and lactating individuals, belong to thesehigher-risk groups.

•

Brain Development: The role of supplemental choline in preventing neuraltube defects during embryonic development remains uncertain; randomized
controlled trials of choline supplementation during early pregnancy are needed
to determine if choline is protective. However, a recent clinical trial involving
maternal choline supplementation during late pregnancy demonstrated
potential cognitive benefits for infants when compared to expectant motherswith lower choline intake levels, suggesting a role for choline throughout theentire pregnancy.

•

Safety Update: Recent research has brought attention to a choline metabolite
known as trimethylamine N-oxide (TMAO), indicating potential associations
between high blood TMAO levels and cardiovascular disease, kidney disease,and type 2 diabetes. However, research in this area shows conflicting results.
Importantly, it is worth noting that elevated circulating TMAO levels might
merely serve as a biomarker of disease rather than being a direct causal factor.

Copper Updates•

Revised Sections on Deficiency: Although instances of dietary copper
deficiency are relatively rare, depletion of copper reserves can arise from
specific genetic conditions such as Menkes disease. Disorders linked tointestinal malabsorption (such as celiac disease, Crohn’s disease, and shortbowel syndrome) and prolonged use of high-dose zinc supplementation canalso contribute to copper depletion.

•

Copper Excess: Copper toxicity from dietary intake is quite rare, but it does
manifest in genetically acquired copper overload disorders like Wilson’s disease.
Even without a genetic predisposition, prolonged consumption of high amountsof copper has the potential to induce liver damage. While numerous studies
indicate that daily doses of up to 10,000 μg (10 mg) pose no risk of liver damage
in generally healthy individuals, there remains concern that this intake level
might result in negative health outcomes.

•

Summarizing Chronic Disease Risk: Copper is involved in several
chronic diseases, including cardiovascular disease, osteoporosis, andneurodegenerative disorders like Alzheimer’s and Parkinson’s disease. The
update to the copper article compiles insights from observational studies andintervention trials that have contributed to our current understanding of these
conditions.

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The full text of the article
on choline can be foundonline at:
lpi.pub/MIC-choline

The full text of the article
on copper can be foundonline at:
lpi.pub/MIC-copper

Continued from Cover

These groundbreaking discoveries were shared througha series of scientific articles and his seminal book,
The Nature of the Chemical Bond. But, even as Pauling’s
theories reshaped the global understanding of atomic
bonds, he set his sights on deciphering the structures oflarger and more complex molecules.
In the 1940s, Pauling was determined to unravel the
intricate structures of proteins. Unlike the relatively
simple molecules Pauling worked on previously,
proteins contain thousands – if not tens of thousands –of atoms and determining their structures represented
new levels of difficulty.

A US Postal Service stamp issued in 2008
commemorates the career of Dr. Linus Pauling,
recognizing his contributions to the field of
molecular biology, his characterization of thehemoglobin protein, and the molecular basis ofsickle-cell anemia.

Proteins are strings of individual amino acids. With his
knowledge of chemical bonds and molecular structures,
Pauling realized that certain patterns were likely todevelop. He proposed the groundbreaking concept thatamino acids formed a coiled helical shape, which turned
out to be one of the foundational components of protein
structures, known as the alpha helix.

The Origins of Orthomolecular Medicine
When Pauling was in his late thirties, he was diagnosed
with Bright’s disease, also known as glomerulonephritis,a serious kidney affliction. During that era, this diagnosis
was akin to a death sentence because an effective
treatment did not exist.

The significance of the alpha helix was immense, as it
was a structural pattern that manifested in a diverse
array of proteins. Armed with this innovative insight,
Pauling’s research into protein structure surged
forward, culminating in the elucidation of the structureof hemoglobin, the iron-containing protein necessary to
carry oxygen in our blood.

Fortunately, Pauling sought the care of Dr. Thomas Addis,
a physician who proposed a unique and unconventional
strategy to manage the disease. Addis recommended
that Pauling restrict his protein and sodium intake.

“Pauling did not just have an impact onmolecular biology, he helped start thescientific field.”Thanks to his wife Ava Helen and her unwaveringcommitment, Pauling was able to stick to this dietary
protocol for years. As a result, Pauling witnessed aremarkable turnaround in his kidney health, defying theodds of the time.

–Chris Petersen

In 1949, Pauling and his research team coined the term“molecular disease” when they characterized the aminoacid structure of hemoglobin type S, the atypical formof hemoglobin that causes sickle cell disease.

Some people have speculated that this health crisis
demonstrated to Pauling the power of good nutrition.
However, Pauling’s research would not directly focus on
nutrition until the mid-1960s, when he announced that he
was interested in the application of vitamin megadoses
for the treatment of mental health conditions.

At the time, proteins were the new frontier, and theimportance of DNA was still shrouded in mystery. Yet,Pauling’s discovery of the alpha helix heralded a new fieldof study – one that would be called molecular biology.

In 1967, he published his first treatise on “orthomolecularmethods” in psychiatry, which would eventually evolve
into what Pauling would term “orthomolecular medicine.”
In essence, Pauling’s orthomolecular medicine theory
postulated that optimal health hinges on the precise
deployment of the right molecules in the right amount at
the right moments.

In 1954 he was honored with the Nobel Prize in
Chemistry for his monumental discoveries of the
intricacies of chemical bonds and the complex
structures of molecules.
This accolade was remarkable in its own right, as itmarked the first instance where the Nobel committee
acknowledged a chemist for a complete body ofwork instead of a solitary eureka moment. It wasvery important to Pauling to be recognized in this
distinguished manner.

Pauling believed that mental health conditions emerged
when key vitamins did not reach the brain properly. Thus,
he suggested that large oral doses of vitamins might
be necessary to restore balance and allow the brain tofunction normally.
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These ideas were soon applied to vitamin C when Paulingreceived a letter from Dr. Irwin Stone, a biochemist who
had been using vitamin C to improve his health for years.
Stone’s theories about vitamin C sparked curiosity within
Pauling, who then embarked on a journey of personal
exploration and research.

A Place to Call His Own
During the late 1960s, Pauling’s fascination withvitamin C grew immensely. He sought the support of
Stanford University, where he was then employed, toestablish a research center that would allow him toadvance his vitamin-related theories. However, Stanford
declined his request, prompting Pauling to make apivotal decision to part ways with the university.

A unique aspect of human evolution is our inability
to produce vitamin C, a trait that sets us apart frommany other creatures. This caught Pauling’s attention,
prompting him to draw connections between otheranimals’ ability to produce vitamin C and our lack thereof
and laid the groundwork for the development of what we
now know as the megadose theory.

Instead, Pauling and his supporters rallied to establish
their own research institution in 1973. Originallychristened the Institute of Orthomolecular Medicine(see picture below), it was co-founded by Dr. Pauling,
Art Robinson, and Keene Dimick.

Pauling’s advocacy of megadoses of vitamin C soon
captured public attention, particularly with the
publication of his book, Vitamin C and the Common Cold,in the early 1970s. In the book he recommended
high-dose vitamin C supplementation to prevent
respiratory illnesses, sparking debate on the potential
health benefits of vitamin C.

Yet, a challenge emerged soon after its establishment:
the chronic issue of securing research funding. Paulingalready had a controversial reputation at the time
the Institute was established. Combined with theunconventional nature of his approach to vitamin C
research, the Institute struggled to obtain grants fromconventional sources.

“Because we’re not able to synthesize
our own internal vitamin C... Pauling
believed that we were often living in astate of suboptimal health.”Thus, the Institute often relied heavily on private
donations. This required Pauling and his team to devise
innovative strategies to sustain their endeavors. Oneof these was rebranding the institution as the Linus
Pauling Institute of Science and Medicine.

–Chris Petersen

However, as public opinion of Pauling rose and fell, so
did the Institute’s financial support.

Subsequently, Pauling collaborated with Scottish
physician Dr. Ewan Cameron on new publications thatelevated the discourse on the role of vitamin C in cancer
treatment. This work would eventually pave the way forthe use of intravnous vitamin C in the treatment of cancer.

Examples of this are evident throughout Pauling’s
prolonged and highly publicized fight over vitamin C in
the treatment of cancer. In 1976, Pauling and Cameron
published Cancer and Vitamin C, suggesting thatvitamin C may be an effective treatment to extend thelife of cancer patients.

Today, Pauling’s career is often distilled into his roleas “the vitamin C guy.” It is remarkable that he started
this quest at an age when many people think about
retirement.

This was a boon for the Institute, as Pauling’s supporters
gave more donations to support this work. On the other
hand, when more and more people turned to vitamin C
as a “natural” cure for their cancers, this irritated somephysicians who saw Pauling’s work as professional
overreach by a scientist into the field of medicine.

Indeed, he was a proponent of vitamin C andorthomolecular medicine for the last three decades of hislife. However, Pauling’s quest to change the way we view
nutrition was not without its consequences.

Continued on page 6

The Institute of Orthomolecular Medicine was
the original name for the Institute, established as a
non-profit organization in May, 1973, it was located in
an office building in Menlo Park, California.
In 1974, the Institute’s Board of Associates officallyrenamed it to the Linus Pauling Institute of Scienceand Medicine. Due to his international fame andrespect, attaching Pauling’s name to the organization
helped provide needed research funding.

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Continued from Page 5

By 1990, however, the Institute was in a state of
upheaval. Leadership changes and reorganization
efforts to refocus on its orthomolecular medicine roots
did little to gain new research funding. New work on
vitamin C and heart disease generated some public
interest but also created divisions within the Institute.

Under immense pressure by Pauling’s supporters to
explore vitamin C as a potential cancer therapy, theNational Cancer Institute eventually consented to start
clinical trials. When initial results were not promising,incredible debates erupted between Pauling and
Dr. Charles Moertel, the lead investigator in the clinicalstudies at the Mayo Clinic.

Dr. Ewan Cameron died in 1991, effectively ending theInstitute’s cancer research program. In the same year,
a ninety-year-old Linus Pauling was diagnosed withadvanced prostate cancer.

In January 1985, the friction seemed to come to ahead when the Mayo Clinic released the results of theirsecond trial on vitamin C and cancer. In this report andin the publicity that followed, Moertel branded vitamin C
as ineffective for cancer treatment.

It was at that point that the daily operations of theInstitute came under the care of Pauling’s son, Dr. Linus
Pauling Jr., and the Institute’s CEO, Stephen Lawson.
Many speculated that the Institute’s days were over,
but Lawson and Pauling Jr. were convinced that a new
strategy was needed.

The Institute was caught off guard by the report.
Pauling and Cameron vehemently contested thesefindings, labeling the Mayo Clinic study as fraudulent
and denying the assertion that Moertel had closely
replicated their methodology.

Although Pauling battled his cancer for three more
years, his journey ended in August of 1994. After his
death, Linus Jr. and Lawson exacted a plan to associatewith Oregon State University.

By then, the damage was already done. Pauling – andby extension, the Institute – now had a tarnishedreputation. Many journals and newspapers refused to
publish Pauling and Cameron’s rebuttals or only did
so too late. As public opinion shifted, the Institute’s
financial standing faltered.

In 1996, the Institute transitioned from California toOregon State University and was renamed the Linus
Pauling Institute, ushering in a new chapter of success.
Its new director, Dr. Balz Frei, elevated the research
profile of the Institute to what it is today.

While some research stirred up controversy, there wereother projects in the Institute that yielded financial
gain. For instance, research into using vitamin C as atreatment for HIV/AIDS attracted donations, especiallyfrom the San Francisco Bay Area. Researchers at theInstitute also began exploring the effect of phytic acid incancer prevention, a program that was almost entirely
supported by a philanthropist based in New York.

Now entrusted to Dr. Emily Ho, the Institute continues
the pursuit of scientific excellence that honors thePauling legacy.

The Linus Pauling Institute of Science and Medicine
and its staff, taken in 1989. The Institute moved to alarger research facility in Palo Alto, California in 1980.

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“COME FLY WITH ME” RECAPOn July 11, Dr. Alysia Vrailas-Mortimer presented the webinar Come Fly with
Me: New Tools to Investigate Parkinson’s that centered on her approach toresearching age-related neurodegenerative diseases using fruit flies – and the
new capabilities that fruit fly research affords to the Linus Pauling Institute.
Below are two key takeaways from Dr. Vrailas-Mortimer’s enlightening talk.
More details about the Vrailas-Mortimer laboratory can be found in the
Spring 2023 edition of the LPI Research Newsletter.

P38 is a protein of interest for aging.

Alysia Vrailas-Mortimer
Associate Professor,
Department of Biochemistry
and Biophysics,
Oregon State University

The recording forthis webinar is now
available online at
lpi.pub/FlyWebinar2023

Dr. Vrailas-Mortimer’s research focus is the function of a protein called p38, apivotal player in the aging process. When the gene encoding p38 is removed, aging
markedly accelerates, resulting in a significantly reduced lifespan. Conversely,
genetically engineering the flies to express extra copies of this gene triggers aremarkable 37% increase in the fly’s lifespan.
Additionally, flies lacking the ability to produce p38 have impaired locomotor
abilities: they move more sluggishly and struggle to regain balance upon falling.
Vrailas-Mortimer explained, “Despite their young age, these flies exhibit behavior
akin to advanced age.” Again, engineering the flies to make higher-than-normal
amounts of p38 protein delays the onset of locomotor challenges that typicallydevelop with aging, allowing them to function better when they get older.
Both processes appear to involve oxidative stress. Flies lacking the ability to makeany p38 protein experience elevated oxidative stress throughout their bodies.
The neurons involved in the development of Parkinson’s disease are especiallyaffected. In contrast, flies engineered to produce extra amounts of p38 exhibit
minimal signs of oxidative stress.

“Superfruit” to the rescue?
Exposure to certain chemicals can heighten Parkinson’s disease risk. Instancesof this phenomenon have been observed with certain herbicides, resulting in
Parkinson’s cases among both humans and animals. Vrailas-Mortimer is interested
in whether antioxidants could help safeguard neurons from deterioration after
exposure.
To explore this in fruit flies, Vrailas-Mortimer procured dietary supplements at
a local grocery store. These included a composite “superfruit” blend (rich inantioxidants from five different fruits) and pure acai berry. Ginger supplements
were used as a control due to their comparatively low antioxidant content.
When flies lacking the gene to produce p38 were provided a standard diet or adiet infused with the ginger supplement, they experienced the accelerated aging
process described above. Supplementation with either the “superfruit” blend or theacai supplement extended their lifespan close to that of a normal fly.
And, the “superfruit” or the acai supplements also prevented these flies fromdeveloping age-related deteriorations in locomotor activity and aided in preserving
their circadian rhythm.
While these supplements showcased promising results, applying these findings
to humans presents challenges. During the Q&A session, Vrailas-Mortimer
acknowledged, “Clinical trials involving various antioxidant supplements haveyielded limited success in Parkinson’s.” Beyond dose, she emphasized thattiming is also a crucial factor. “Many clinical trials recruit patients with advanced
Parkinson’s disease,” she explained, “And antioxidant supplementation may beless effective at later stages of the disease.”
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CREATE A LEGACY OF HEALTHWE CAN IMPROVE LIVES FOR GENERATIONS TO COME
with our research and outreach programs. Continuing
the Pauling legacy, the Linus Pauling Institute seeks todiscover and share the new ways that nutrition can help
everyone live longer, better lives.
And you can help make that happen.
We invite you to learn more about how thoughtfulplanning today can help you create a sustaining legacyof health at the Linus Pauling Institute.
Start today by watching the recording of ourCreate Your Legacy webinar online at
lpi.pub/Legacywebinar
Ready for the next step? Contact us to learn more.

LINUS PAULING INSTITUTE
DIGITAL DIGEST
Alexander Michels, Newsletter Editor
Victoria J. Drake, Associate Editor
Sandra Uesugi, Assistant Editor
Oregon State University
307 Linus Pauling Science Center
2900 SW Campus Way
Corvallis, Oregon 97331
phone: 541-737-5075
fax: 541-737-5077
email: lpi@oregonstate.edu
website: lpi.oregonstate.edu