Dr Kevin Clark Talks to InTech About Bioenergetics

June 20, 2012

Bioenergetics, the biology of energy transformations and energy exchanges within and between living things and their environments, is the subject concerning a research area within biochemistry concerned with the study of the structure, composition, and chemical reactions of substances in living systems. InTech's editor of the recently published book titled "Bioenergetics", Dr Kevin Clark, talked to us about this highly-engaging field of study, the latest scientific trends, the aforementioned book as well as his own career.

InTech: Tell us something about your activity as a researcher and your areas of interest

I’ve been involved in research at a professional level for over twenty-five years, dating back to when I was an undergraduate student at Oregon State University. Over that time, I’ve worked with some outstanding scientists located at various institutions, such as Lawrence Ryan, Robert Jensen, Robert Radtke, Ronald Browning, Sydney Fox, Nikos Logothetis, Edward Eisenstein, and others. I employ my education and training in engineering, psychology, biophysics and biochemistry, physiology, and neuroscience to explore a great many areas of interest in basic and clinical science. Examples include my work on biomechanisms mediating neural and aneural plasticity, expression of intelligence within and across taxonomic and technological boundaries, new treatments for intractable neurological and infectious diseases, and application of microbe-based technologies as sensor, command, and control platforms.



"There are a number of progressive degenerative metabolic diseases for which an understanding and application of bioenergetics principles are used in attempts to treat patients."

My research interests perhaps tend to be broader than most scientists. This situation results from a need to satiate my many curiosities and serves as a useful way to strengthen my interdisciplinary knowledge. I’ve always felt that it is through the integration of ideas learned from multiple areas of science that one often develops significant insights. And I’ve been fortunate in my career to have had several important scientific discoveries. The latest of these is relevant to the field of bioenergetics and stems from both theoretical and experimental questions concerning the physical, biological, and behavioral bases of microbial social intelligences. Some microbes are capable of learning to elevate their information processing to quantum levels of performance, possibly through intracellular store-operated calcium reaction-diffusion. In social contexts, this improvement in information processing enables faster, more efficient, and less error-prone adaptive decision making. Better decision makers achieve ecological advantage over less skilled microbes by being more socially competent as well as by consuming less metabolic energy and by fine-tuning sparser structural resources to reach the same goals. Because the likely bioprocesses underlying these effects are ubiquitous, similar effects might occur for many life forms. Such findings are important for understanding pathogen-host and pathogen-pathogen interactions, major developmental and evolutionary transitions, and other research topics.

InTech: How many edited or authored books have you published?

InTech’s “Bioenergetics” is my first published edited book. At the moment, I’m also editing two more scientific volumes. One of these books, entitled “Social Learning Theory: Phylogenetic Considerations across Animal, Plant, and Microbial Taxa”, is contracted through another publisher and should be ready to launch in late 2013. The invited book prospectus of my third collected volume, entitled “Microbial Intelligences”, is now being considered for publication as a single edited book, a new volume for a continuing book series, or an inaugural volume for a new book series. I also been invited to submit a book prospectus for an authored textbook intended for a university/college undergraduate core course in sociobiology. This book is now in the initial stages of preparation.

InTech: You are the editor of the book “Bioenergetics". What is the scope of the book?

The book's scope reflects the broad scope of the discipline of bioenergetics. Bioenergetics, technically the transformation of biological fuels by cells, helps determine how life originates, sustains itself, and evolves. Thus, the study of bioenergetics informs the study of every level of biological description, from biosphere to habitat to organism to system to tissue to cell to molecule. InTech's book “Bioenergetics“ conveys these biological relationships to readers through chapters that address the molecular biology, systems physiology, and organismic biology of bioenergetics. Readers of this book will learn about where bioenergetics as a field of study has been in the past and where it hopes to be in the future. Exciting themes in current and future research advances can be found in the book, including discussions involving the role played by bioenergetics in aging, metabolic disease, and performance optimization.

                                                                                                       "All living systems are open ones"

InTech: Bioenergetics, a field of biochemistry, generally concerns the study of all processes which require production and consumption of energy in living systems. Where do living systems obtain this energy?

All living systems are open ones. That is, instead of being self-contained, they must interact with their surroundings to collect and dissipate energy. Life forms acquire the potential energy for metabolic sustenance from ambient or host environments. These “foods” or fuels often must be first broken-down, catabolized, or “digested” by many organisms into manageable macromolecules – complex sugars, proteins, and fats – for later conversion of energy and use as raw materials. Once in this form, these molecules are again altered by sequences of chemical reactions, such as the catabolism of glucose via glycolysis, to yield simpler products for ATP biosynthesis. Anaerobic microorganisms, those that evolved and live without oxygen, can produce all the energy they need from anaerobic glycolysis or other fermentations with no net change in oxidative state. However, aerobic organisms, such as animals, require another major step called the citric acid cycle. The citric acid cycle increases energy production by complete oxidation of the glycolytic endproducts lactic acid and pyruvate. The reduced electron carriers created from the citric acid cycle enter the redox chain of cellular respiration that then generates energy-rich ATP from oxidative phosphorylation and chemiosomotic coupling. In contrast, plants and photosynthetic microbes drive energy conversion through capture of radiant fuels or light in the visible spectrum. Photonic energy is passed from light-harvesting antennae to photopigment-containing reaction centers of photosystems. There water is cleaved, oxygen is evolved, and reduced electron carriers are created. Photophosphorylation during light reactions and chemiosmotic coupling next drive the synthesis of ATP from ADP and inorganic phosphate. Exceptions to these examples exist. But regardless of the organisms involved (i.e., microbes, plants, or animals), energy stored in ATP is transported to cellular locations where it is liberated for biological work through the breaking of phosphodiester bonds.

InTech: What amounts of energy can be derived during chemical processes and for what is this energy utilised?

I will concentrate on several examples to keep my answer brief. For oxidative metabolism, 36 to 38 molecules of ATP are produced per mole of glucose oxidized, depending on the energy cost of shuttle systems. Prokaryotes and other cells that employ the glutamate-aspartate shuttle expend no energy when transferring reducing equivalents to mitochondria. However, cells which use the glycerol phosphate shuttle loose 2 total ATP molecules to deliver reducing equivalents to the respiratory chain. ATP hydrolysis releases -30.5 kJ/mole of exergonic free energy for biological work, such as biosynthesis and active molecular transport. For two-system photosynthesis, approximately 48 photons must be absorbed to yield 18 ATP molecules via noncyclic photophosphorylation. Hydrolysis of these ATP molecules helps fix atmospheric carbon dioxide into carbohydrates during the dark reaction. Cyclic photophosphorylation also yields ATP for biological work. In addition to oxidative phosphorylation and photophosphorylation, a process called substrate-level phosphorylation produces GTP and ATP from super high-energy compounds important to glycolysis and the citric acid cycle.

InTech: If there is a bioenergetics imbalance, what can it lead to?

Well, this is an interesting question because it can be viewed from both micro- and macroscopic levels of physical organization, each reciprocally interacting with the other. When one thinks about bioenergetics imbalances, the imbalances of metabolic diseases probably first come to mind. Metabolic diseases can be inherited or acquired. They oftentimes produce dysfunctional enzymes, abnormally low concentrations of enzymes, or no enzymes essential for proper cell energetics. Imbalances may yield low energy production or transport and harmful levels of bioreactants or bioproducts. These conditions stress cellular function and may cause cell death and, consequently, organism death under extreme perturbation. Many metabolic disorders exist in humans and animals, such as sugar intolerances (e.g., galactosemia), organic acidemias (e.g., maple syrup urine disease), amino acid metabolism defects (e.g., phenylketonuria), mitochondrial diseases (e.g., Wolff-Parkinson-White syndrome), ganglioside/lysosomal storage diseases (e.g., Tay-Sachs disease), and glycogen storage disorders (e.g., Von Gierke’s disease). Common symptoms of metabolic disorders in humans and animals include developmental retardation, neurological impairments, thoracic and visceral organ failure, and fatigue/lethargy. In addition to cellular and organismic levels of description for bioenergetics imbalances, one can imagine effects at the larger biosphere scale. Remember that all life on Earth exists in delicate interactive states between and within dynamic systems. For example, the oxygen consumption and carbon (dioxide) emission needed for the metabolism of aerobic organisms dramatically affect photosynthetic organisms. And the oxygen evolution and carbon (dioxide) fixation needed for the metabolism of photosynthetic organisms likewise affect aerobic organisms. Cells behave as engines when transforming potential energy into biologically useful energy. Defective cell energetics impairs engine performance. Biospheres also behave as engines, cyclically producing products that maintain life. If the biosphere becomes irreversibly imbalanced, such as might occur through habitat destruction, pollution, species-specific lethal diseases, and other factors, then the biosphere engine breaks-down. Such imbalance at the biosphere scale could flourish to the point of global life extinction. For instance, the evolved bioenergetics pathways of organisms and cells would be challenged by unfamiliar poor nutrition availability (e.g., low atmospheric oxygen, scarce food supplies, etc.) and/or additional habitat changes (e.g., sudden climate shifts) that increase energy demands. Without the appropriate biological substrate and niche restrictions, even healthy organisms simply cannot adequately perform the bioenergetics processes needed to sustain life.

InTech: Also, can bioenergetics and some of its principles be used for treating or curing currently incurable diseases?

Of course, there are a number of progressive degenerative metabolic diseases for which an understanding and application of bioenergetics principles are used in attempts to treat patients. A few of those diseases were mentioned in my answer to a previous question. Sometimes early diagnosis through genetic testing or other methods, dietary changes, medication (e.g., enzyme replacement, antioxidants), and organ transplant can ameliorate symptoms and elevate quality of life. However, many diseases remain incurable, such as Tay-Sachs disease. The hope of medical scientists is that gene therapy, stem cell therapy, and smart drugs will eventually cure/treat refractory diseases, including metabolic ones. But strong clinical evidence remains elusive for most cases. Another promising clinical area for bioenergetics applications is cancer therapy. Cancer cells require high metabolism to live and proliferate. Cancers poorly treated by standard methods can be controlled by selectively disrupting or preventing oxidative phosphorylation or aerobic glycolysis. In particular, experimental work to suppress oncogenes which encode metabolic substrate, to lower metabolic rate via glycolytic enzyme inhibitors, and to alter metabolic cycles via respiratory chain inhibitors, phosphorylation inhibitors, uncoupling agents, transport inhibitors, and Krebs cycle inhibitors may lead to real clinical successes.

InTech: What is the role of bioenergetics in stem cell maintenance and aging?

No clear explanation of aging exists. Many biological premises favor evolution- , gene- , and disease-based mechanisms which incorporate aspects of bioenergetics. Some leading explanations that involve cell energetics include programmed cell death, accummulative DNA damage and mutation, faulty cellular metabolic waste disposal, and free radical formation. For example, new research into the cross-kingdom symbiosis and coevolution of organisms has provided insight into adaptive metabolism, apoptosis, transmissible diseases and immunoprotection, and other issues germane to the relationship between bioenergetics, aging, and disease. Some findings suggest, perhaps unsurprisingly, that organisms evolved over time to become energetically efficient in certain niches of variable climate, food supply, and dietary demands. But as those niches deviate beyond acceptable parameter ranges, the same organisms, such as humans, show increasing vulnerability to cytopathogenesis via oxidative stress and other mechanisms. This effect is believed to occur because inherited bioenergetics pathways encoded in mitochondrial DNA accummulate deliterious mutations, accumulate toxic/dysfucntional byproducts, or lag in adapting to the requirments of a new “host“ niche, such as incongruous changes in organism caloric intake and work. What ever the reasons for aging, changes in environmental signals and tissue integrity may induce somatic stem cell proliferation and differentiation to recover or renew tissue function and viability.

InTech: Are there any significant research developments currently being explored which are aimed at generating new insights for the field of bioenergetics?

My answers to earlier questions partly address this question. Certainly clinical application of bioenergetics to understand and treat diseases and aging have produced significant research findings and insights about bioenergetics processes and the influence bioenergetics has on organism lifespan and health. Much of this work focuses on the limits of cell efficiency, protection, and repair, on mitochondrial target sites for therapeutics, and on genetic and epigenetic control over the transmission and expression of metabolic states (e.g., diseases, regulation of cell homeostasis, polymorphic phenotypes, etc.). Basic research into bioenergetics is also beginning to uncover a wealth of information regarding the molecular biology of, among other topics, cellular energy transport and byproduct disposal, response regulator networks, nucleotide metabolism, mitochondrial upregulation, calcium signaling, and ion channel structure and function. I think these areas of research will generate very powerful insights into bioenergetics as scientists differentiate the classical and quantum nature of gene mutation, epigenetic modification, chemical reactions, network behavior, and molecular configurations critical for highly efficient and adaptive cell energetics. Some of this work is now being accomplished for photosynthetic bacteria, enterobacteria, ciliated protozoa, and animals.

InTech:  What kind of audience will benefit most from reading this book?

“Bioenergetics” is a scholarly work intended for a university/college- educated audience versed in biochemistry and biophysics, cell biology, genetics, molecular biology, and physiology. The contents of the volume provide comprehensive reviews in experimental and theoretical bioenergetics as well as coverage of new developments in research and technology. Graduate students, academicians, and nonacademic professionals, such as medical industry scientists, wild life biologists, and sports technologists, should find the book most beneficial for their trade or professional activities. But precocious readers with a beginning interest and less formal education in bioenergetics also might find the book useful and interesting, despite possibly being technically challenging.

InTech: What are your future plans or your next projects?

As I mentioned in my answer to a preceding question, I have several book projects that I plan to finish in the near future. I also expect to soon publish more research, review, and opinion articles in peer-review journals and to patent and license several more inventions involving my work in microbial intelligences. In addition, I’m currently participating in a few international consortiums emphasizing new directions in the study and interpretation of biological information processing and its relationship to information theory and physics. Sometime in late 2012 or early 2013, I hope to move to Vienna, Austria to conduct research with Richard Wagner at the Konrad Lorenz Institute and Michael Wagner at the University of Vienna. The research project(s) will be aimed at further testing my ideas on microbial sociality which continue to be developed from my observations of ciliate mate selection.

InTech: Now that you have edited an Open Access book, do you feel there are more benefits to it in comparison to traditional publishing?

I think that the open access revolution in publishing has its advantages and disadvantages. Of course, the great advantage of open access publishing is that the cost of publishing a book or article is not passed on to the target audience, making the publication more easily available to those interested in reading it. This condition limits reader disenfranchisement and improves the dissemination of information when readers have reasonable access to online resources and when the direct and indirect costs of publication are manageable. However, the burden of publication costs has not been eliminated by open access models. Cost margins have been instead reallocated to authors and other financial sources, such as advertisers and donors. As the tradeoff between content accessibility and financial burden increasingly disenfranchises poorer authors, the open access concept of publishing fails. Under this situation, neither reader nor author benefits because the diversity of circulated information lessens. Putting considerations of information dissemination aside, additional factors, including ecological sustainability, figure into the success or failure of open access publishing. I suspect that the carbon footprint of traditional publishing models likely exceeds that of electronic-based open access models, even though open access publishing is not free of environmental impact in terms of energy production and usage, industrial and consumer wastes from electronics manufacturing, and installation of associated technological infrastructure. However, given the relative short period that open access publishing has existed to any significant level, it might take a while for the model’s environmental impact to be well understood.

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About Dr Kevin Clark

Kevin ClarkKevin B. Clark earned his Doctorate of Philosophy from the Program for Biopsychology of Learning and Memory at Southern Illinois University in 1999. He has held basic and/or clinical research appointments at Oregon State University, Southern Illinois University, and the Max-Planck Institute for Biological Cybernetics. Among other professional activities, Dr. Clark has served as member of ten professional societies, referee and associate editor for professional journals, editor of collected volumes, and long-time consultant and collaborator to the Research and Development Service at the Veterans Affairs Greater Los Angeles Health Care System. Dr. Clark has spent much of his research career using his diverse training in disciplines of engineering, psychology, biochemistry, physiology, and neuroscience to study the evolution and biological basis of learning, memory, and intelligence. Dr. Clark’s award-winning research and patented inventions improving learning, memory, and recovery from traumatic brain injury through peripheral neuromodulation gained recognition from MacArthur fellow Dr. James McGaugh and other members of the National Academy of Sciences, USA. Later comparative primate studies conducted with systems neuroscientist Dr. Nikos Logothetis focused on Dr. Clark’s interests in the neural basis of learning, memory, perception, and cognition across animal phylogeny. His broader interests in the evolution of intelligent behavior largely began in graduate school while briefly working with molecular and cellular evolutionist Dr. Sidney Fox on protocell models of learning and memory and continue today with his most recent research studying quantum, relativistic, and Kaluza-Klein aspects of microbial conflict mediation and instigation, particularly heuristic-guided social reciprocity learned by ciliates during intra- and intermate selection. By creating paradigms comparing microbial learning and goal-directed behavior with animal decision making, Dr. Clark has shown microbes to behave as soft-matter quantum computers. The major implications of Dr. Clark’s ground-breaking findings regarding learned microbial social behavior have been acknowledged by noted experts worldwide. His work extends to many topics, including host-parasite and pathogen-pathogen interactions, cellular decision making, NMDA-receptor-dependent plasticity, nervous system repair, evolution of social behaviors and intelligences, adaptation to extreme environments, and emergence of evolutionary and developmental transitions. Dr. Clark is now preparing patent applications exploiting primitive microbial intelligences for next-generation medical, industrial, and national defense biotechnologies.


Interview by:

Ana Nodilo, nodilo@intechopen.com