Undeterred by conventional wisdom or his lack of physician’s credentials, Nobel laureate James D. Watson, Ph.D., co-discoverer of the structure of DNA, is forwarding a bold hypothesis— diabetes arises from a deficiency in biological oxidants. This hypothesis directly opposes the usual view, which holds that diabetes is caused by an excess of biological oxidants, or reactive oxygen species (ROS). Biological oxidants are widely believed to cause inflammation that is harmful to pancreatic cells.
Watson first presented his hypothesis in an article that appeared online February 27 in the Lancet. The article, which is entitled “Type 2 diabetes as a redox disease,” will also be on the cover of the Lancet’s U.S. print edition dated March 1–7. In this article, Watson makes it clear that he developed his hypothesis by considering the role of exercise.
“Physical exercise has long been widely regarded as essential to human health,” Watson writes. “Yet, we do not know how exercise-stressed skeletal muscle cells that generate reactive oxygen species such as hydrogen peroxide delay—if not prevent—the occurrence and severity of diseases such as type 2 diabetes (as well as dementias, cardiovascular disease, and some cancers).”
Exercise is recommended for patients with incipient type 2 diabetes—those with high blood sugar levels. In fact, patients often begin exercise before they begin receiving glucose-lowering drugs such as metformin. It struck Watson that while exercise and metformin seem to help not only patients with diabetes, but also patients with cancer, Alzheimer’s disease, and cardiovascular disease, the reasons behind the benefits remain unclear.
How could exercise, which prompts the body to make large numbers of oxidants, protect against diabetes, which presumably arises from inflammatory processes caused by an excess of oxidants? Perhaps oxidants and their role in inflammation needed a closer look. Clearly, pancreatic tissue in people with type 2 diabetes is indeed inflamed. But could the inflammation be due to something other than an excess of oxidants?
The body’s cells cannot survive without making both oxidants and antioxidants. “There is a delicate balance between the two,” Watson observes. In a cellular organ called the endoplasmic reticulum, hydrogen peroxide, a well-known ROS, helps forge chemical bonds, which stabilize proteins as they fold.
Watson suggests that when there is not enough oxidation in the endoplasmic reticulum, proteins emerge unfolded and cannot function. This, he proposes, causes the inflammation that harms the pancreas, sometimes causing type 2 diabetes.
Watson’s thinking is described by a press release issued by Cold Spring Harbor Laboratory, where Watson is chancellor emeritus: “Watson suggests [that] exercise, which promotes oxidation, plausibly can have a beneficial effect on those with high blood sugar. Such benefit would be lessened if not abolished, he speculates, if such an individual consumed large quantities of antioxidants—just as athletes who take large quantities of antioxidant supplements do not seem to benefit or benefit less from their exertions.”
The release indicates that Watson is planning a scientific meeting at Cold Spring Harbor Laboratory later this year, which he hopes will launch a larger scientific effort to investigate the mechanisms through which exercise improves health. “Just about every doctor I've ever known tells every patient who is capable of doing so to exercise,” notes Watson. “I think exercise helps us produce healthy, functional proteins. But we really need to have some high-quality research to demonstrate this.”