Exclusive Interview with Mitochondrial Medicine Pioneer Douglas Wallace
Mitochondrial medicine pioneer Douglas Wallace is the subject of MitoWorld’s first “Spotlight” feature, in this case a 40 minute interview, conducted by life sciences journalist Daniel Levine, with a page of citations and links.
Wallace’s career, discoveries and insights cover the fields of mitochondrial genetic medicine from its beginning to trying to unraveling the issues of Long-Covid and novel approaches to cancer treatment.
Last May, I was lucky enough to visit the Wallace Laboratory at Children’s Hospital Philadelphia (CHOP), one of the most extensive and exciting mitochondrial research centers in the world. For those who don’t know Douglas Wallace, if there was a mitochondrial medicine hall of fame, Wallace would be its first member.
The Wallace Lab is a very impressive entire floor of researchers and the most advanced storage specimens, latest imaging and analysis equipment. The lab environment is congenial and professional. But most impressive is Wallace – soft-spoken, witty, insightful and encyclopedic. A biology convert from physics, Wallace’s work fifty years ago studying the genetics of the mitochondrion which provides the powers for every aspect of human and all animal biology. However, for Wallace, the frustration has been immense, because the traditional worlds of medicine and biological have not shifted their focus to include the central role of energy and thus mitochondria and in health and medicine.
In his Spotlight interview, Wallace points out, “What’s happened is that we have NIH institutes that are all organized around anatomy. And we have clinical departments all organized around anatomy. So as a result, we don’t have a unifying view of how bioenergetics affects all the different health problems we have. [1] So what we really need is to find ways to bring this community together. Now, one area that’s been done in the primary mitochondrial disease area is an organization like the United Mitochondrial Disease Foundation (UMDF), which has worked hard to bring families together with clinicians to help children. But we don’t have that kind of structure for the common diseases.”
According to Carlos Moraes, PhD, Esther Lichtenstein Professor in Neurology at the University of Miami, who has been studying the pathobiology of mitochondrial diseases and related disorders for more than 30 years, “In the 1970s, Doug Wallace started a revolution in genetics by showing that the mitochondrial genome is inherited exclusively from the mothers and can confer distinct phenotypes to the cell. His work set the stage to trace the origins and migrations of humans and to the understanding of a large group of mitochondrial diseases.” [2] Moraes’ current focus is on mtDNA gene editing with nucleases and base editors.
Wallace’s SARS-CoV-2 collaborator Afshin Beheshti, PhD, University of Pittsburgh Professor of Surgery and Computational and Systems Biology, speaks to their on-going work.
“In the context of COVID-19, our research has revealed that SARS-CoV-2 directly targets mitochondria, leading to systemic mitochondrial dysfunction that persists in long COVID patients. This groundbreaking work has the potential to uncover mitochondrial biomarkers and therapeutics, offering new avenues to address long COVID, which continues to affect millions globally.”
On both the lighter side and the deeper side, Wallace’s mind and writing has made direct parallels between bioenergetics and the Chinese medicine concept of “Chi,” or energy flow. [3] Martin Picard, Associate Professor of Behavioral Medicine in the Departments of Psychiatry and Neurology at Columbia University Irving Medical Center, supports Wallace’s wider view. “Doug has been a ray of light for the field, illuminating possibilities for mitochondrial science and medicine. Mitochondria are indeed the vehicle for Chi – supporting the life-giving energy transformation that power the mind and the flow of human consciousness.”
On the deeper side, Wallace’s physics roots and knowledge of the evolutionary role of ATP producing ancient bacteria led to the modern eukaryotic life-building cells led to a fascinating paper on the connection between “energy flux” and “biological information stored in nucleic acids.”
Complex structures are generated and maintained through energy flux. Structures embody information, and biological information is stored in nucleic acids. The progressive increase in biological complexity over geologic time is thus the consequence of the information-generating power of energy flow plus the information-accumulating capacity of DNA, winnowed by natural selection. Consequently, the most important component of the biological environment is energy flow: the availability of calories and their use for growth, survival, and reproduction. [4]
[1] A mitochondrial bioenergetic etiology of disease, 2013, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614529/
[2] A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine, 2005: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821041/
[3] Mitochondria as Chi, 2008, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429869/
[4] Bioenergetics, the origins of complexity, and the ascent of man, 2013, https://www.pnas.org/doi/full/10.1073/pnas.0914635107
