In late 1951 Pauling and Itano enlisted the help of Dr. George Burch, the physician from Tulane University who supplied Caltech with sickle cell blood samples, to perform clinical trials on people suffering from sickle cell anemia. Pauling and Itano thought that the sickling process could be obstructed and suggested treating sickle cell anemia patients with carbon monoxide and sodium nitrate therapies. Burch agreed to conduct the clinical trials and immediately submitted a proposal for a Guggenheim Fellowship, which he received.

Itano wrote a brief protocol for the clinical trial in early 1952. After many delays, Dr. John C. Paterson started the trials in early 1953 by following the procedures developed by Pauling and Itano. Thus, Paterson administered sodium nitrate intravenously and orally in varying doses. The methods proved unsuccessful because the patients' hemoglobin could not be converted safely without causing toxicity and anoxia.

By 1954 they stopped the trials because satisfactory results were not produced. Itano did not publish the negative findings and a few years later, Dr. Ernest Beutler tried a similar clinical trial using sodium nitrate to treat sickle cell anemia. Beutler, a physician at City of Hope Medical Center in Duarte, California also found that sodium nitrate was too toxic to justify its use.