Disease Is Evolution-in-Reverse
Majid Ali, M.D.
To understand the beginning of diseases, we first need to understand the beginning of life. This is impossibly complex one way and very simple in an another.
Simply stated, evolution is the long (and continuing journey) which allowed the development of modern human cells from the primordial “pre-cells” (spherules that lived in he toxic primordial soup). Pre-cells were acid-producing, free-radicalized fermenting cell. Every chronic disease begins wit fermentation in cells. To put it in the prevailing jargon, all forms of inflammation begin with cellular fermentation. It is really that simple. This is what I mean by evolution-in-reverse.
Oxygen Models of Diseases
All my Oxygen Models of Diseases (listed at the end of this article) are based on the above-mentioned facts of life. Why fuss about oxygen models of diseases. Simply because no treatment of ny chronic disease can be considered scientifically complete without detecting and addressing the fundamental cellular energetic defect in fermenting and inflamed cells.
The Origin of Life Explains the Origin of Disease
Majid Ali, M.D.
A disease is a state of regression—evolution in reverse, so to speak. In the late 1980s, I conceived this simple idea and saw the possibility that the origin of disease, at its core, could be understood through an understanding of the origin of life on the planet Earth. I recognized that the origins of both life on the planet and disease share one fundamental commonality: fermentative metabolism. Evolution delineated the path of emergence from toxic primordial soup—from simple fermenting unicellular life forms to modern highly sophisticated humans and animals—and the disease state traverses that course backward—to the primordial highly acidic and toxic soup of our origin. From toxic primordial to toxic cellular soup!
A Eureka Moment
The simple notion that disease states represent a reversal to primordial conditions hit me with the energy of a eureka moment. In a flash, I discerned the possibility of finding answers not only to the so–called mystery maladies—fibromyalgia, polyarthralgia, chronic fatigue syndromes were among those in vogue then—but also the fundamental energetic-molecular basis of common degenerative disorders, such as diabetes, heart attacks, and strokes. During the next decade, I focused on high-resolution phase-contrast mircoscopy of living blood cells and the study of ATP generation in Krebs cycle. Specifically, I looked for evidence for respiratory-to-fermentative (RTF) shift in cellular ATP energy generation—yeastization of human cells, so to speak.
In 1998, I published an extensive survey of origin-of-life studies and added my own clinical, biochemical, and microscopic observations in The Journal of Integrative Medicine. I chose the title “Oxidative Regression to Primordial Cellular Ecology (ORPEC)” to underscore the importance of the for respiratory-to-fermentative shift
in chronic diseases. I followed that with several studies in which I correlated metrics for various clinical and pathological entities with the degrees of RTF shift. In all twelve volumes of my textbook “The Principles and Practice of Integrative Medicine,” I attempted to look at health/dis-ease/disease continuum through the prism of oxygen homeostasis with an evolutionary perspective. Simply stated, I sought to eaxmine how toxicities of foods, environments, and thoughts—deep disappointment of life have reached unprecedented scales—imperil fundamental cellular energetics and set the stage for the development of disease.
Respiratory-to-Fermentative (RTF) Shift in ATP Generation
Simply stated, in a disease state the high-efficiency respiratory-ATP generation is degraded to a low-efficiency fermentative ATP production. I introduced the term dysoxygenosis—dysox for short—to refer to this degrative metabolic shift. To explain the basic idea to my patient, I also introduced the term dysfunctional oxygen metabolism for dysoxygenosis. With this introduction, below I present some of the classical origin-of-life scientific studies.
In 1953, Nobel Prize-winning chemist Harold Urey and his student Stanley Miller completed their classic experiment on the chemical origins of life. They took methane, ammonia, and hydrogen, the gases present on the early Earth, and applied an electrical spark discharge to them to create conditions of lightening. This led to their a stunning discovery that amino acids, the compounds that make up the proteins in all living organisms, can be generated in the laboratory. This also provided evidence of a theoretical model of how elements could have come together to produce simple molecules— ammonia and methane, of course, were among the prime suspects then—which, in turn, were linked together to build larger and complex compounds. The absence of oxygen in the Miller-Urey soup is noteworthy in the present context. The core tenet of the ORPEC model of the origin of disease, of course, is also impaired or dysfunctional oxygen metabolism—mimicking the primordial, reducing ambient conditions.
Darwin on Origin of Life
I called the tenth, eleventh, and twelfth volumes of my textbook The Darwin and Dysox Triology. I named my diabetes book Oxygen, Darwin’s Drones, and Diabetes, and plan to include his name in two more title. I do so for many reasons. Here is one of them: On February 1, 1871, in a letter to his friend, Joseph Dalton Hooker, Darwin expressed his thoughts on the probable origin of life with the following words: [Life probaly began in a] “warm little pond, with all sorts of ammonia and phosphoric salts, lights, heat, electricity, etc. present, so that a protein compound was chemically formed ready to undergo still more complex changes”.
The sage was prescient! His words preceded the work of Stanley Miller and Harold Urey, which provided firm experimental evidence for this view, by 82 years.
I might add here one more reason for my fondness for Charles Robert Darwin: the Darwin Principle in integrative medicine. In 1998, I proposed this principle with the following words: No part can be understood without understanding its relationships with the whole. We can neither know the genes without knowing the micro-ecologic conditions prevailing in the cells, nor understand those conditions without learning about genes. I commonly invoke this principle when I want to expose the harm done by the frivolous single-disease-single-drug clinical trials, which form the basis of the long-term use of blocker drugs administered concurrently with a host of other drugs.
Bada’s Prebiotic Soup
It is easy to see that in the highly charged, superheated, and chaotic conditions of the early Earth, the earliest forms of amino acid would have been unstable and would have rapidly been degraded. The work of Jeffrey L. Bada, the eminent marine chemist at the University of California, is notable. He conceived and conducted experiments to show the primordial amino acids could have acquired stability. It is self-evident that the Earth had to have cooled down enough for water to appear and create the conditions of solubility and then yet more complexity and stability.
Fifty-four years after the Miller-Urey original experiments, Bada fortuitously discovered some of Miller’s residual extracts and re-analyzed them using far more sophisticated technology than was available to the original investigators. To his great surprise, his team found that the discharge spark experiment had actually generated about 30 compounds, not merely the five identified by Miller in 1953.
The Miller-Urey story took another revealing twist with the studies of 1969 Murchison meteorite. Initially, the meteorite was thought to contain about 75 amino acids. Forty years later, the comparison of the distribution of amino acids of the Miller-Urey spark experiment, were found to be closely similar to those in the meteorite.
The Amino-to-RNA Leap
Then must have come an evolutionary challenge: how to develop a mechanism of replication with some measure of fidelity so that the early complex molecules could be reproduced in a robustly regulated fashion. RNA was assigned this role. RNA eventually begot DNA. But how did simple amino acids evolve into RNA to monitor their own replication? This became what may be designated as the “amino-to RNA leap” puzzle.
The RNA seemed too complex to have evolved directly from the simple molecules of the primordial soup. Many intermediate forms evolving with a multitude of mutations were postulated—a billion years in the making by some estimates—to produce molecules with survival advantages and capable of making copies of themselves.
RNA to DNA for a Self-replicating Systems
For decades, life in the contemporary context— an energetically self-sustaining and self-replicating system—was considered to have followed an amino-to-RNA-to-DNA script, in which DNA controlled all life. RNA stands for the molecule ribonucleic acid, while DNA is short for deoxyribonucleic acid. In the history of great scientific discoveries, the celebrated crown-wearers are often eclipsed by the lowly precursors. And so it was with RNA, a smaller, more versatile player that is not only able to store information, like DNA, but also to use information to catalyze reactions.
In 1989, Sidney Altman shared a Nobel Prize for delineating new roles of RNA. He characterized RNA in simple words: “It uses energy, it sustains itself and it replicates.”
Four Stages of the History of Oxygen on Planet Earth
The story of the origin of life, as well as of the origin of diseases, cannot be told well without an outline of how nature chose oxygen to drive human evolution. The ability of primordial energy systems to split water and release oxygen into the ambient air was the seminal event which set the stage for the evolution of oxygen-driven and oxygen-orchestrated cellular energetics. I present this vast subject in a series of companion tutorials, most notably one entitled “The History of Oxygen on planet Earth.”
Two Systems of Oceanic Bioenergetics
Available evidence points to oceans as the original site of the origin of planetary life. Nature evolved two divergent systems of oceanic bioenergeticss: a “top-ocean” solar-driven system and a “deep-ocean” sulfur-based system. Sunlight penetrates ocean waters for only three to four hundred feet, limiting photosynthetic energy generation largely to such depths, which is designated as the top ocean. Photosynthesis evolved, by current scientific evidence, more than two billion years ago to harness sunlight to split water and release free oxygen, which initiated the development, differentiation, and expansion of the kaleidoscope of marine and terrestrial oxygen-loving (oxyphilic or “philic”) species.
The second system of oceanic bioenergetics evolved in the deep ocean—5,000 to 30,000 feet and deeper—independent of solar energy. Unable to harness energy from bound oxygen, primordial life forms in deep ocean became oxyphobic (“phobic”). The early precursors of phobic life took form around vents of the deep ocean that seeped hydrocarbons—methane gas being the best recognized form—enriched with sulfur and iron compounds. So began the sulfur and nitrogen economies of the deep ocean. Phobic microbes that produce nutrients create the conditions under which complex multicellular life developed. The bowels of the deep-ocean shrubs and trees today are filled with such microbes.
Fibrillating Philic-Phobic Equilibrium
The “philic-phobic equilibrium,”which evolved over a period of about two billion years ago, is now under serious cumultative threats of global overpopulation, climatic chaos, planetary chemicalization, diffuse “oceanic plasticization,” and biodiversity. By some accounts, the accumulation of plastic waste now suffocates marine life in swaths of the Pacific that equal more than half of the Atlantic Ocean. All these geologic-scale changes have in common two crucial elements: oxygen depletion and incremental oxidative stress—conditions that potently favor phobic life over philic life.
Land-based photosynthetic biomass far exceeds its aquatic counterpart. However, marine phytoplankton carry out almost half of the global net photosynthesis, since the rate of photosynthesis per unit of biomass of the former is much lower than that of the latter. This facet of the philic-phobic equilibrium has profound implications for oceanic regeneration following massive disruptions, notably for the potential proliferative response times of microbial assemblages to varying rates of oxygen depletion and layers of oceanic redox potentials.
Fermenting Bowels, Fermenting Oceans
I return to the title of this tutorial: the origin of life explains the origin of disease. I see a parallel in oceanic fermentation and fermentation in a baby’s bowel which sets the stage for a host of inflammatory and immune disorders. Oceans ferment for decades after massive oil spills, such as seen after the Exxon Valdez disaster in Alaska and Deepwater Horizon in the Gulf of Mexico. Similarly, a baby’s bowel ferment for months and years after they are brought up on sugar and antibiotics, as regrettably many children are. Their delicate ecologic balance between oxygen loving (oxyphils) microbes and oxygen-shunning (oxyphobes) microbes are disrupted with severe long-term consequences in development and growth. .
Bowel fermentation, and the leaky gut state which develops as its consequence, occurs in children and adults when threats to bowel ecology are neither detected nor addressed. In my experience, the most sinister threats include mold allergy, mycotoxins, adverse food reactions, toxic metals, environmental pollutants, and chronic disappointments in life. Inflammatory and immune deficiencies develop as the consequences of such threats and often lead to widespread systemic effects.
Clinical ecologist are aware of neurotoxicity states caused by marine neurotoxins produced in excess during red tides of oxygen-depleted ocean water. It seems safe to predict that wide swaths of the Gulf of Mexico will ferment long after the gushing Deepwater Horizon geyser is stopped. Phobic microbes will continue to ferment and unleash poisonous red and crimson tides years after the spill is arrested, whenever that occurs. This happened on smaller scales in past oil spills and is likely to occur on a much larger scale this time.
Physicians and Eco-sensitivity
Each massive environmental tragedy underscores the need for a deep sense of “eco-sensitivity” for physicians. Each time the response of the medical community at large is deeply disillusioning. This happened with the Ixtoc-1, Exxon Valdez, Kuwait War, the Twin Tower inferno, the Iraq War, and now with the Gulf’s gushing geyser of boiling tar.
Each time such a tragedy causes a large loss of human life. I hope that The New England Journal of Medicine will recognize the convergence of the molecular consequences of terror and toxicity. I hope it will clearly see the essential need for holisim in medical thinking. How I hope it will reconsider its pernicious opposition to environmental medicine, nutritional medicine, and energy medicine. Each time the Journal’s obfuscation of real issues is reprehensible.
I discussed the profound relevance of the top-ocean life to human health and disease in Darwin, Oxygen Homeostasis, and Oxystatic Therapies (2009) the tenth volume of The Principles and Practice of Integrative Medicine.8 The deep-ocean life has drawn little, if any, attention from physicians in the past. This—it seems safe to predict—will change with the unfolding Deepwater Horizon catastrophe in the Gulf of Mexico. The long term human health consequences of this massive disruption of the philic-phobic equilibrium among the zones of varying oxygen conditions and redox potential in the Gulf of Mexico will not be known for decades.
Science of the Origin of Life and Clinical Medicine
Scientific knowledge, understanding, and wisdom advance when seemingly unrelated— paradoxical or divergent, in some instances—lines of evidence converge to firmly establish scientific facts. This principle is as crucial for physicians as it is for others in various scientific disciplines. The study of seeming paradoxes and discordances in nature is not only necessary for reconciling apparent contradictions—no true contradictions really exist—but also for developing deeper perspectives on natural phenomena. As school children, doctors learn about photosynthesis and splitting of water to generate free atmospheric oxygen. Then these fundamental subjects disappear from their radars forever, taking away with it an understanding of oxygen, carbon, and hydrogen ecomonies of the human body. This is unfortunate since it also takes oxygen off their clinical radars except when their patients gasp for breath with asthma, stroke, myocardial infarction, and similar life-threatening illnesses. In all twelve volumes of The Principles and Practice of Integrative Medicine, my unfaltering focus is on the issues of disrupted oxygen signaling and impaired oxygen-driven mitochondrial ATP generation in the clinical management of all chronic nutritional, environmental, immune, degenerative, and neoplastic disorders.
For additional reading on the subject, I suggest my book Oxygen and Aging (2000), available at www.aliacademy.org