Prior to starting the Linus Pauling Institute, Pauling had worked at Stanford University
where he met Dr. Paul L. Wolf, Associate Professor of Pathology and Director of the Clinical Laboratories at Stanford's
medical center. In 1971 Pauling and Wolf discussed starting clinical trials on sickle
cell anemia sufferers by way of orthomolecular methods using vitamin C, urea, and
nicotinic acid (also called niacin). Pauling had heard promising things about niacin
from Hoffer; thus, he was confident that "n. [nicotinic] acid would be much more effective
than either ascorbic acid [vitamin C] or urea." About one year later, Wolf responded
that niacin did not block or reverse sickling and that research on niacin no longer
Pauling and Wolf drafted a proposal for trials to search for an anti-sickling agent
through dietary control. They believed that there was a relationship between metabolism
and diet, which could aid prevention and treatment of sickle cell anemia. They proposed
to analyze the urine of sickle cell patients in hopes that the urine test might "throw
light on the mechanism of sickling and the reasons for the occurrence of crises of
Wolf suggested to Pauling that they submit a funding proposal to the National Heart
and Lung Institute for research on sickle cell anemia. As a result of the 1972 National
Sickle Cell Anemia Control Act, the United States government allocated large amounts
of money to research on sickle cell diseases, including $92,000 to Pauling and Wolf.
Using a portion of these funds Wolf and his colleagues found that prostaglandins,
fatty acids manufactured by bodily tissues that act on other parts of the body, can
induce sickle cell crises. Sickle cell crises are painful episodes, lasting for days
or weeks, experienced during periods when the blood flow slows because of distorted
blood cells. Wolf and his co-workers then searched for drugs to treat the crises.
Pauling, Robinson, and other researchers at the Linus Pauling Institute used the funds
to analyze urine in hopes of determining chemical changes between periods of crises
and relative health among sickle cell disease sufferers. Pauling and Wolf devised
another clinical trial in the summer of 1972 using vitamins C and E for sickle cell
patients. The concept for this trial arose from Pauling's desire to prove the efficacy
of vitamin C.
In the early 1970s, Pauling unsuccessfully solicited for funding to conduct research
on sickle cell patients using nutritional therapies by means of orthomolecular medicine
from the International Sickle Cell Anemia Foundation and San Francisco's Sickle Cell
Anemia Research and Education, Inc.