Denham Harman, 1916-2014

Denham Harman

Denham Harman

Today we remember Dr. Denham Harman, a colleague and friend of Linus Pauling who passed away last November at the age of 98.  Harman and Pauling explored the influence of chemistry on the human body at a time when the link between chemistry and medicine was just beginning to be considered scientifically.

Harman and Pauling first met at the University of California, Berkeley in the 1930s, where Harman was conducting his undergraduate work and Pauling was serving as a guest lecturer.  Harman wound up completing a Ph.D. in chemistry from Berkeley in 1943, during which time he was also employed at Shell Oil Company where he conducting chemical research. The Shell years would take on a special importance as, in Harman’s recollection, many of them “were devoted almost entirely to free radical chemistry; largely of oxygen and of compounds of phospherous and sulfur.”

In 1949 Harman left Shell Oil for Stanford University, where he earned an M.D. in 1954.  Following internships and residencies in the Bay Area, Harman accepted a position at the College of Medicine at the University of Nebraska, remaining there for the entirety of his career.

In 1954 Harman published “The Free Radical Theory of Aging,” an article in which he suggested that, over time, the chemical reactions that constantly take place in the human body produce unstable byproducts – free radicals – which in turn interfere with the body’s normative functions and result in aging and age-related conditions, like dementia.  The idea emerged during a spell as research associate at UC-Berkeley’s Donner Laboratory of Medical Physics. As Harman recalled

To me Donner was unique; my time was my own except for Wednesday mornings in the Hematology Clinic.  I took advantage of this free time to pursue a long-time interest in the library; the possibility that aging might have a single basic cause.  My wife first called this subject to my attention.  In December 1945 she showed me an article in the current issue of the Ladies Home Journal entitled, “Tomorrow you may be younger.” This article by William Lawrence, science editor of the New York Times, was concerned with the work of Dr. Alexander Bogomolets of Kiev.  An English translation of Dr. Bogomolet’s book, The Prolongation of Life, was published in 1947. […]

The first four months at Donner was a period of progressively increasing frustration. I began to wonder if I was chasing a will-o-the-wisp; maybe there was no single cause of aging, and if there was, maybe it could not be perceived because of incomplete biological knowledge. The frustration ended one morning during the first part of November. While reading in my office it suddenly occurred to me that free radical reactions, however initiated, were responsible for the progressive deterioration of biological systems with time.

Harman’s theory was based on the potential impact of unstable chemical byproducts, or free radicals, as they built up in the body. In chemistry a compound is considered a free radical if it is formed by the loss of an electron. Previous studies had shown that free radicals stimulate the decomposition of organic matter by reacting with surrounding compounds. It had also been found that different substances called antioxidants act as agents that prevent free radicals from reacting with other compounds, thus slowing the process of decay.

Harman’s work applied this basic knowledge to the human body. His conclusion was that aging could be defined as a deviance from the body’s chemical norm, and he compared aging to a disease. The free radical theory of aging also ramped up attention to the role of antioxidants in the body. Harman’s theory proposed that reactive oxygen species were among the most harmful and that antioxidants could, to a certain extent, ameliorate the aging process, a concept which to this day drives an industry based on antioxidant supplements.

Linus Pauling first heard of Harman’s theory in 1956 and quickly became a supporter. Harman and Pauling’s work had individually led each of them to similar conclusions; namely, that health depends on having a proper chemical balance in the body, a concept that fell under Pauling’s terminology of “orthomolecular medicine.”

In 1979 Pauling entered into the conversation about free radicals in the human body by discussing the implications of the existence of the newly discovered superoxide, a free radical that is formed during metabolism as a byproduct of oxygen reduction. In his paper “The discovery of the superoxide radical,” Pauling noted how the existence of this toxic free radical was predicted by quantum mechanics but had remained undiscovered until 1979. The existence and toxicity of this naturally occurring chemical byproduct was seen by Pauling as being in support of Harman’s theory.

It is now known that reactive-oxidant chemicals, like superoxide, can in fact be harmful to an organism and contribute to aging. But no specific set of chemicals is entirely responsible for the processes that occur when the body begins to age.  Harman’s idea, in effect, was too blunt.

Regardless, Pauling remained impressed by the work.  In a 1989 award nomination letter, he wrote

I became interested in the general question of aging and death about 35 years ago. Before long I learned about Dr. Harman’s free radical theory of aging, and I have continued to be interested in it. As the years have gone by, much information has been gathered about the importance of free-radical mechanisms in biochemistry, including the process of aging and the cross-linking of protein molecules. I consider that Denham Harman made a very important contribution to our understanding of aging, through his formulation of the theory.

Indeed, while Harman’s theory was unable to help “cure” aging, as he had hoped, his research into the role of free radicals in metabolic processes has inspired new ideas on how to deal with other age-related health concerns, such as cancer and age-related memory loss. While current research has suggested that aging is more complex than was proposed by Harman, the free radical theory is to this day taken into consideration by researchers in many fields.