Dr. Weeks’ Comment: Upon retirement, many scientists like Professor Emeritus Don Huber are able to speak a truth which we all need to heed. Who is Dr. Don Huber? His is a scientist and public servant whose agricultural research over the past 50 years has established him as one of the world’s top plant scientists. He now urges transparent and collaborative work because the evidence that GMOs “…directly increase Oxidative Stress, which in turn upregulates Formaldehdye and down regulates Glutathione…” means that GMOs create poisoned, cancer-causing food.
DON HUBER STATEMENT
I have independently reviewed the four (4) papers from the recent research work of Dr. V.A. Shiva Ayyadurai, Ph.D. and his research team at the Systems Biology Group at the International Center for Integrative Systems concerning C1 Metabolism, Oxidative Stress and Genetic Modifications (GM).
This set of four papers is the first comprehensive, scholarly and detailed analysis, using modern methods from computational systems biology, based on a thorough review of the scientific literature, which conclusively shows that in crops with genetically modified organisms (GMOs), formaldehyde, a known carcinogen, is upregulated at the molecular level, while glutathione, a master anti-oxidant, is downregulated, providing definitive scientific results to end the debate and controversy on whether GMOs are “substantially equivalent” to non-GMOs.
The first paper (Paper 1) provides the foundational systematic review of the literature, which serves to identify three (3) key molecular pathways of C1 Metabolism. C1 Metabolism, as the authors share, is one of the most fundamental molecular pathways in plants, bacteria and fungi. Paper 1 is comprehensive, detailed and has derived the important molecular pathway elements of C1 Metabolism.
The second paper (Paper 2) provides the first computational systems model of C1 Metabolism, derived using the molecular pathways from the systematic review in Paper 1. The model in Paper 2 clearly shows that, without perturbations from oxidative stress or GM modification, in the natural state, formaldehyde is cleared to zero levels rapidly and does not accumulate. In addition, the results show that glutathione levels are maintained at a steady state level in normal conditions. Formaldehdye is not only a toxic molecule but also an important regulatory marker of proper plant function.
The third paper (Paper 3) systematically performs a literature review on Oxidative Stress molecular pathways, using the same methods as in Paper 1 in the series. Three molecular systems of Oxidative Stress are derived to model Oxidative Stress. This Oxidative Stress model is then integrated with the C1 metabolism model derived in Paper 2. The simulation results of the integration of the models of C1 Metabolism and Oxidative Stress serve to show how Oxidative Stress upregulates Formaldehyde and downregulates Glutathione. What is particularly comprehensive about Paper 3 is that the parameter sensitivity analysis demonstrates that even wide variations of critical kinetic rate constant parameters, continues to consistently yield definitive upregulation of Formaldehyde and downregulation of Glutathione.
Paper 1, Paper 2, and Paper 3 are seminal pieces of work that lay a solid foundation, based on modern computational systems biology approaches, to support the research findings of the fourth paper (Paper 4). Paper 4, based on recent findings in the literature, provides a review of critical enzymes that are upregulated by GM and their direct effects on Oxidative Stress. These variations are integrated with the integrative model of Oxidative Stress and C1 Metabolism, (of Paper 3), in a methodological fashion to demonstrate that GM modifications directly increase Oxidative Stress, which in turn upregulates Formaldehdye and down regulates Glutathione.
What is most compelling of these four series of papers is that, as the authors conclude, this approach provides a new framework for rationally approaching the debate and controversies surrounding the discussion on substantial equivalence of GMOs. The approach the authors have taken provides an opportunity for both pro-GMO and anti-GMO people to have a transparent and collaborative conversation on the leveled playing field of molecular systems biology, in order to really understand what is different and “equivalent” about GMOs versus non-GMOs.
As someone who has dedicated his research efforts to plant pathology, I can with confidence state that this is breakthrough work and deserves the proper attention in both the layperson media as well as in the scientific and medical communities. Their work demonstrates with great clarity that plants are complex systems and simply manipulating one aspect of plant function, without understanding how such modifications affect the integrity of other systems, is reductionist and can lead to erroneous conclusions between cause and effect.
BIOGRAPHY OF DON HUBER, PH.D.
Dr. Don Huber is Professor Emeritus of Plant Pathology at Purdue University, West Lafayette, IN. He received B.S. and M.S. degrees from the University of Idaho (1957, 1959), a Ph.D. from Michigan State University (1963), and is a graduate of the US Army Command & General Staff College and Industrial College of the Armed Forces. He was Cereal Pathologist at the University of Idaho for 8 years before joining the Department of Botany & Plant Pathology at Purdue University in 1971. His agricultural research over the past 50 years has focused on the epidemiology and control of soil-borne plant pathogens with emphasis on microbial ecology, cultural and biological controls, and physiology of host parasite relationships. Research also includes nitrogen metabolism, micronutrient physiology, inhibition of nitrification, and nutrient-disease interactions. In addition to his academic positions and research, Dr. Huber retired in 1995 as Associate Director of the Armed Forces Medical Intelligence Center (Colonel) after 41+ years of active and reserve military service. He has received various awards for his scientific accomplishments and contributions to government. Dr. Huber is an active scientific reviewer; international research cooperator with projects in Argentina, Australia, Brazil, Chile, China, Costa Rica, Denmark, Germany, Guatemala, Japan, Mexico, and Russia; and a consultant to academia, industry, and government. He is author or co-author of over 300 journal articles, Experiment Station Bulletins, research presentations, book chapters and review articles; 3 books, and 84 special invited publications. He is internationally recognized for his expertise in the development of nitrification inhibitors to improve the efficiency of N fertilizers; interactions of the form of nitrogen, manganese and other nutrients in disease; herbicide-nutrient-disease interactions; techniques for rapid microbial identification; and cultural control of plant diseases. Dr. Huber is former APS coordinator of the USDA National Plant Disease Recovery System (NPDRS) and a member of the Threat Pathogens Committee.