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Rusting from Within
The Dark Side of O2

by Pamela Weintraub

Feature One

Posted December 21, 2001 · Issue 117


Free radicals produced as by-products of aerobic metabolism in mitochondria contribute to certain neurodegenerative diseases and aging. At the forefront of the fight against these scavengers, the Oxygen Society and its members seek to understand the mechanisms of free radical damage and develop interventions to slow the damage.

Mention "oxygen society" and you cannot help but evoke the image of some posh Los Angeles club with interior chambers of pumped-in, purified oxygen, and potent elixirs of juniper, eucalyptus, and sage. When it comes to oxygen clubs, a search of the Internet shows those of a pro-oxygen mindset to be plentiful, indeed. But unbeknownst to the public, say some world-class scientists, the proprietors of these establishments have made a mistake.

Oxygen is both essential and toxic.

Enter a different type of oxygen club: the Oxygen Society, a group of scientists determined to set the oxygen worshippers straight. It is our very metabolism of oxygen, and the resulting toxic by-products, that causes cancer, neurodegeneration, aging, and death, the society says. Established only 15 years ago and already boasting an elite membership of more than 1,200 scientists, including three who have recently won the Nobel Prize, the California-based society has a mission statement that should leave no one confused: "The Oxygen Society was established in 1987 in response to a growing recognition of the 'dark side' of oxygen as a major issue for the life sciences. The oxygen paradox tells us that oxygen is both necessary for aerobic life and toxic to all life forms. Free radicals and active oxygen species now touch every biological and medical discipline. Efforts to counteract the damage caused by these species are gaining acceptance as a basis for novel therapeutic approaches, and the field of preventive medicine is experiencing an upsurge of interest in medically useful antioxidants."

According to Kent Lindeman, executive director of the society, the group leads the charge against this Darth Vader of the body through its conferences, workshops, education programs, and especially its journal, Free Radical Biology and Medicine, the preeminent peer-reviewed publication in the field. Recent issues carried articles on such weighty topics as cell death, the impact of iron and manganese on the production of free radicals, oxidative stress in athletes during extreme endurance exercise, and oxidative stress in the brain during bacterial meningitis.

Colleagues scorned Harmon for saying we rust from the inside.

The first scientist to recognize the oxygen paradox - life's requirement for a fuel that destroys life - was Denham Harmon, a chemist as well as a physician. It was back in the 1950s that he first compared the production of free radicals, the charged, reactive oxygen molecules generated as we breathe, to the relentless production of rust. It was as if we were rusting from the inside, quite literally, Harmon proposed, prompting the scorn of colleagues who viewed his theory as absurd.

In the intervening years, most life scientists have come to understand that Harmon was right - that free radicals produced as by-products of metabolism in mitochondria, the cellular energy factories, do indeed cause neurodegenerative disease, from Parkinson's and Alzheimer's to garden variety senility, and increasingly damage the DNA and proteins we need to stay young.

Society members seek to understand free radical damage.

At the forefront of the fight against these scavengers, the Oxygen Society and its members seek to understand the mechanisms of free radical damage and develop interventions to slow down the damage. And according to the society's president, Matthew B. Grisham, a molecular and cellular physiologist at Louisana State University Health Science Center at Shreveport, Louisana, aging and neurodegeneration are just two of many kinds of research the society supports.

One research focus is on arteriosclerosis, where plaque in the blood vessels is thought to be caused by oxidative stress. Other members study cancers, which are often precipitated by free-radical destruction of DNA.

Grisham studies the role of free radicals in inflammatory disease.

Grisham, meanwhile, investigates the role free radicals play in sustaining inflammatory disease like rheumatoid arthritis, colitis, and inflammatory bowel disease. Grisham states that while an infection or autoimmune problem can trigger these disorders, his notion is that free radicals keep the problem going over long periods of time.

Grisham's work is an example of just how far the society has come. While its first decade was devoted mainly to reactive oxygen species, scientists now understand that large amounts of reactive nitrogen, also produced during metabolism, and a host of other molecules may be destructive as well. In one line of research, Grisham's lab is studying the genes activated by oxygen and nitrogen species in hopes of understanding their role in modulating immune responses. In another set of studies, he is using animal models to learn if and how reactive oxygen and nitrogen initiate or sustain inflammatory disease. "What are the mechanisms for damaging the joint in arthritis?" he asks. "We think that oxidative and nitrosative stress and a cocktail of damaging free radicals are involved."

Frei advocates increased dietary intake of antioxidants.

Oxygen Society president-elect Balz B. Frei, director of the Linus Pauling Institute at Oregon State University, meanwhile, is studying the antioxidant effects of vitamin E. At the forefront of a national effort to raise the recommended daily amounts of certain antioxidant micronutrients above present levels, Frei has produced an impressive body of literature documenting the health benefits of increasing our intake of the antioxidant vitamin E. Other members have done likewise for another antioxidant, vitamin C.

As for the future of the society and its members, Grisham notes that the goal is to intervene where nature has left off. "There is only so much we can do with jungle juice biology," he says. "We have to make better, more potent antioxidants in the lab." When the job has been done, predicts Grisham, we may not live any longer than we would have, otherwise, but we will live out our years in a state of better fitness and health.

Antiaging research will be highlighted at the 2002 annual meeting.

The society is pushing these plans along. It expects some 700 researchers from around the world at its November 2002 meeting in San Antonio, where there will be a focus on antiaging research, among other things. Moreover, in its colossal battle against the "dark side" of oxygen (not to mention nitrogen), the society is not alone. Executive director Lindeman points out that his group has allies. At the international level, the Oxygen Society represents North and South America within the International Society for Free Radical Research (SFRR International), he says. SFRR International currently has four regional members societies: SFRR Europe, SFRR Asia, SFRR Australasia, and the Oxygen Society itself. And smaller groups feed in. There is an oxygen club of scientists in Greater Washington, D.C., and another, smaller but like-minded club in California, just down the road.

Pamela Weintraub is a former staff writer at Discover, former editor-in-chief of Omni Internet, and the author of 15 books on health and science.
Matt Morrow is a freelance illustrator from Omaha, Nebraska.

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Mitochondria, Oxygen Free Radicals, Disease and Ageing - examines the mechanism of superoxide generation in the mitochondria, the evidence relating to damage associated with free radical production in certain neurodegenerative diseases, and the evidence connecting oxygen free radical production with aging. From Trends in Biochemical Sciences, 2000, 25:10:502-508. Full text available from BioMedNet.

Evidence of Oxidative Damage in Alzheimer's Disease Brain: Central Role for Amyloid-Peptide - reviews recent advances. From Trends in Molecular Medicine, 2001, 7:12:548-554. Full text available from BioMedNet.

Free Radicals in the 20th Century, A Sting in the Tail of Electron Tracks, and Do Mitochondrial Mutations Dim the Fire of Life? - several recent articles from Science magazine. Paid subscription required for full text.

DNA and Dementia and Trying to Unlock the Mysteries of Free Radicals and Antioxidants - two related articles from The Scientist.

Free Radical Biology and Medicine - an online journal published by the Oxygen Society.

Linus Pauling Institute at Oregon State University - news, articles, and information on the role of nitric oxide and oxidative stress in disease and aging.

Oxidative Stress and Aging Association - offers extensive information, news, articles, and resources.

Society for Free Radical Research - an excellent gateway to news and information on free radicals, including full-text articles from the society's journal, Free Radical Research.

Aging Research Centre - gives researchers in various fields access to the latest information on the aging process.

Nitric Oxide Home Page - a clearinghouse of information for anyone interested in the biological roles of NO.

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