Stem Cell Therapy Based on the Stem Cell-Organism Theory
Stem cells injected directly to the heart (photo derived from Supercell, HBO documentary films. Internet. Jan 10,2013)
Mindoro pine leaves whose stem cells differentiated into roots (Photo courtesy of Ms. Rene S. Fontanilla, Ph.D.)
Protozoa, an elementary multi-celled organism that causes malaria, undergoes differentiation in a mosquito and a human being
To formulate a theory to serve as basis of stem cell therapy
Our purpose is to come up with a theory that serves as basis of stem cell therapy.
The procedure is to come up with a stem cell-organism theory then make it as basis of stem cell therapy.
A theory consists of concepts and relationships among concepts (Einstein, A. Ideas and Opinions. 1954).
In theory-making, one starts out with a hypothesis that is a guide in research or mind experiment. So we say that a hypothesis consists of concepts and relationships among concepts. Concepts and relationships must be verifiable and once verified, the hypothesis is proven. To repeat: concepts so defined exist. Relationships so defined occur. Once proven, the hypothesis graduates into a theory. Here then is a proposed hypothesis:
“A trigger induces the stem cell to differentiate into a multi-celled organism.”
In above stem cell-organism hypothesis, the concepts are: "trigger," "stem cell" and "multi-celled organism."
The relationships are "induces" and "differentiate."
Definitions with proofs that the entity so defined exists follows.
Definition of concepts
Trigger - it is a substance or hormone that initiates a reaction, either forward or reverse. For example, a hormone is a trigger. The growth factor is a trigger of growth in a human being. A trigger can be a substance or lack of it. Insufficiency of calcium stimulates the parathyroid gland to step up production of parathormone. This hormone signals osteoplasts in the bone to increase production of normal bone calcification (Cranton, E. MD. Bypassing Bypass. Updated 2nd edition. 1996).
The trigger is not the one that will develop into an organism or that provides the materials that will develop into the organism. A trigger can be a stem cell of a sheep or a chicken. Sheep stem cell had been used on a human being but the recipient did not grow fur. It can be a pluripotent stem cell that was formerly an adult cell reprogrammed into pluripotent stem cell.
[To recall our procedure. We define a concept and provide proof that the entity so defined exists. The fundamental form is definite description. (Russell, B. Human Knowledge: Its Scope and Limits. 1947). "Multi-celled organism" is a definite description. "Organism" is not a definite description, it can be considered a name. Existence is attributed to a definite description not to a name. This requirement of a definite description is to guard against fictitious concept or relationship. A name when analyzed further leads to a contradiction, according to Russell.]
A stem cell has its own triggers. However, these triggers can be disturbed by factors within the stem cell or from the environment like free radicals and their derivatives. (That is why there is aging or cancer.) A trigger prepares and induces one stage of stem cell for the next stage; for example, from totipotent stem cell to pluripotent cells.
An enzyme is a trigger. It does not go into a reaction. It serves as a facilitator of inducement. An enzyme is like heat applied on a metal pot. Put water and sugar together in a metal pot and heat the pot; heating up water and sugar. Sugar and water will mix resulting in a gel. Heat triggered the mixing. An enzyme induces mixing without heat.
Inside the body of a human being there is production of hydrogen peroxide, indicated as H2O2. it goes like this: the starting materials are superoxide and hydrogen atom. Superoxide is indicated as O2-1, meaning two atoms of oxygen with one unpaired electron in its outermost orbital. The enzyme superoxide dismutase (SOD) attaches one proton to one oxygen atom of superoxide and another atom of hydrogen to the other oxygen atom. The result is hydrogen peroxide (hydrogen atom consists of one proton and one electron). SOD accomplishes this without additional heat, that is, under normal body heat. (Hydrogen peroxide, a destructive reactive oxygen species, is countered by glutathione peroxidase, turning it into safe water.)
A trigger can be blocked. Take the case of Vioxx, a pain reliever, meaning a blocker or inhibitor. Vioxx blocks the enzyme cyclooxygenase from acting on arachidonic acid. This results in the non-production of thromboxane and prostacyclin. Thromboxane constricts arteries and promotes blood clot. Prostacyclin does the opposite of thromboxane and dilates arteries to allow more blood flow. Lack of prostacyclin results in hypertension and heart attack. (Vioxx, marketed since 2000, was withdrawn from the market in November 2004).
Aspirin is also a blocker but with a better effect than that of Vioxx. Aspirin partially blocks cyclooxygenase allowing production of small amount of thromboxane and prostacyclin whose by-product is small amount of superoxide (Sears, B., Ph.D. The Zone. 1995). The welcome result is that aspirin prevents stroke and heart attack; and reduces incidence of cancer by 40%.
[Without SOD, superoxide will accumulate. Extra superoxide is bad. Superoxide reacts with nitric oxide depleting the amount of nitric oxide that is a signal for the inner wall of the artery to dilate and allow more blood flow. This results in angina for a fellow with heart disease. Superoxide also reacts with nitric oxide and produces peroxynitrite that catches nitric oxide three times faster than that done by superoxide. Superoxide is a free radical; it produces siblings called reactive oxygen species (ROS) that acts like a free radical. Free radicals and ROS cause cancer and heart disease.]
The function of a trigger is different from the function of genes in recombinant DNA of biotechnology. For example, the genes of Bacillus thuringiensis (Bt), a bacterium, in Btcorn. Bt is a natural pesticide in crops like rice and corn, protecting the crop from stem borer, an insect pest. Some genes of Bt were isolated and incorporated into the chromosomes of corn. So Btcorn has some genes of Bt. Btcorn is resistant to stem borer. Bt genes stay as they are in the Btcorn.
The trigger does not transfer any gene to the chromosome of the host stem cell. That is, no gene in the sheep stem cell used as trigger is transferred to the chromosome of the human being.
If the trigger were involved in differentiation there is a possibility that the use of sheep stem cells on a human being might produce fur. So far, the recipient of sheep stem cell has not produced fur.
In some instances, the trigger is not a substance or an enzyme but insufficiency like the insufficiency of calcium.
Why include trigger as a concept? It explains why a human being given stem cells of a sheep does not grow fur.
Stem cell - it is one cell that will develop into a multi-celled organism like a human being. It can be also a plant, like pine tree. This one cell had been the result of fertilization, the fusion of two sets of chromosome. In the case of a human being, one set (23 chromosomes) was contributed by the male and another set by the female. This stem cell carries 46 chromosomes.
A stem cell clones itself. Except in the totipotent stage, some stem cells in each subsequent stage remain in the same status. For example, some stem cells in the pluripotent stage remain as pluripotent cells. We may call these as reserve stem cells. These reserves can be induced by a supplied trigger to differentiate into the next stage; pluripotent induced to multipotent stage.
Circumstantial proof in cloning: Some cells and particles of the cell clone themselves: Killer T cells triggered by foreign invaders; macrophages, triggered by foreign invaders; mitochondria, triggered by exercise or physical conditioning; hemoglobin, triggered by exercise, physical conditioning or acclimatization when one is climbing high and cold places like Mount Everest. .
Multi-celled organism - we are talking of a mufti-celled organism, like a human being or a pine tree. We are not talking about a virus (RNA or DNA) or a bacterium that is single-celled (prokaryotic). We are familiar with a human being as a complete multi-celled organism (eukaryotic) with all the normal organs made up of tissues, and tissues made up of cells. (For brevity, we will use organism, aware that we mean multi-celled organism) An organism has structure, form and function. We are talking of a normal organism. We will consider a fellow with a Down’s syndrome abnormal. (Our apologies: there is no intended prejudice towards someone with this syndrome who carries one extra chromosome in each cell.)
This addition of one chromosome occurs during meiosis. In this hypothesis under discussion meiosis is assumed. A stem cell with such kind of abnormality is excluded in this hypothesis.
[Meiosis is a reproductive process where the 46 chromosomes in a cell of human being are reduced to 23. So the sperm or the egg will contain 23 chromosomes; they unite during fertilization that is why the zygote has 46 chromosomes. The zygote will differentiate into the full term baby. Also during meiosis the genes that control varied characters of the individual get into various combinations. That is why the offspring will differ in character from his/her parents. Furthermore, mutations in chromosomes may occur during meiosis: addition, deletion, substitution. Mutations are heritable. We have left out discussion of the chromosomes in the mitochondria because the genetics of the mitochondrial chromosomes (37 in all) is not yet fully developed unlike that of the 46 nuclear chromosomes. Suffice it to say that we are aware of the chromosomes in the mitochondria.].
Organism includes the information code carrier (deoxyribonucleic acid) in the chromosome, the messenger (ribonucleic acid), structure (skeleton, muscles, skin), form (size, shape, color), and constituency (cells). The messenger transmits the information code that translates into proteins that make up the organism.
Organism also includes limits of growth. A normal earlobe of a human being will not grow as big as an umbrella or bigger owing to continuous growth. There are switches like the gene p53 that when switched on controls growth. The limit is provided by the information code carried by the DNA.
Integrity of the organism is assumed in this hypothesis. It does not matter if it is a result of evolution or owing to creation. What we find is the organism that assumes structure, form and function. An example of function is perpetuation of species that is shown by adults when the male has the ability to produce sperm and the female has the ability to produce the egg.
Integrity is shown in the molecular level. Take oxygen. Molecular oxygen, the kind that we use, has two unpaired electrons in its outermost orbital resulting in instability. However, molecular oxygen grabs other electrons to re-establish stability that is a manifestation of integrity. it may be difficult to understand why oxygen is like that, but it is that way. If oxygen is not that way, there might be no organism like a human being. Molecular oxygen (O22+) that goes into oxidation-reduction is responsible for the production of enough energy for the human being. Anaerobic reaction, without the use of oxygen, cannot produce energy enough for the needs of human being. Integrity ensures survival and perpetuation of species. Integrity also means that if a the liver had been damaged, stem cells would regrow the liver. In fact, the liver can regenerate provided any barrier is remedied. A barrier to liver regeneration is cirrhosis or scarred and hardened liver tissues. There are now several ways to treat and cure cirrhosis.
Conversely, when gene p53 is switched off owing to mutation, growth becomes uncontrolled that results in tumor or cancer. Part of such limit is apoptosis or programmed cell death. In apoptosis, the nucleus of the cell shrinks. No inflammation is involved as would happen in an injured cell. The apoptosed cell is engulfed by healthy cells in the vicinity.
Gene p53 is classified as a gatekeeper gene. Switched on, it prevents the development of colon cancer in two points in the interphase of mitosis, or cell division of adult cells. Interphase is part of cell cycle; other parts are prophase, metaphase, anaphase and telophase.
"Gatekeeper genes control the cell cycle. Mutations in these genes opens the gate to uncontrolled cell division. Tumor suppressor genes and many proto-oncogenes are gatekeeper genes" (Cummings, M. Human Heredity, Principles and Issues. 2009:296).
There is another kind of genes called caretaker genes. These repair mutations, including mutations in the DNA owing to errors in copying and environmental factors like free radicals and their derivatives.
"Caretaker genes encode proteins that maintain the integrity of the genome, including DNA repair genes" (Same source as above, emphasis supplied).
Integrity is equivalent to the law of conservation of matter in physics. It was Faraday who first made this assumption that was carried over by Einstein. There is a design for man or for a woman. A stem cell will fulfill that design. Evolution may change that design. However, for every stage of evolution, the design that emerged will be fulfilled by the stem cell.
Definition of relationships
Induce – going through one phase to another phase either forward or reverse. For example, the collision of the molecules of water until such molecules separate then evaporate. The process starts with water and ends up as gas. The inducement is forward. Water vapors cluster onto a particle to form a raindrop – this is reverse.
The stem cells of a sheep induced the differentiation of human stem cells. A fertilized chicken egg induced differentiation of human stem cells, according to a Filipino doctor.
Inducement had been demonstrated in a pine tree species, Mindoro pine (Pinus merkussi de Vries) whose leaves look like needles. For her doctoral dissertation, Ms. Rene S. Fontanilla, Ph.D. conducted an experiment involving the inducement of rooting in leaves of this tree. One group of leaves served as control, that is, no synthetic and concentrated trigger was used. Another group of leaves (treatment groups) were applied with synthetic concentrated triggers, naphthalene acetic acid (NAA), indole butyric acid (IBA) and Superthrive. The treatment groups produced significant number of roots. That is, the production of roots are clearly attributed to the presence of synthetic and concentrated trigger. Therefore, NAA, IBA and Superthrive induced differentiation of stem cells in the leaves that resulted in roots.
Editing as of March 4,2013.
The control group grew a statistically insignificant number of roots. That is, the production of roots cannot be clearly attributed to any cause. The most likely cause of root production is the native nutrient in the soil medium used in growing the control leaves. The practical implication of the native nutrient growing roots is that the native nutrient is not reliable for use in growing roots. This is especially so if you want to mass produce seedlings out of needle fascicles to plant a wide area of forest land. The theoretical significance of the native nutrient growing roots is that the needle fascicles contain stem cells that are induced to differentiate. I have another Hub that explains this phenomenon. End of editing.
As we know, the leaves of a pine tree does not naturally grow roots. The triggers, NAA, IBA and Superthrive, induced its production of roots. This was a research in cloning conducted in 2008 for a dissertation at the University of the Philippines Los Baños campus. This was the first time in the world that leaves of Mindoro pine was induced to produce roots. The hypothesis that Mindoro pine can be cloned by means of its leaves has been proven. Planted in the soil, the rooted leaves will grow trunk, branches, leaves; bear flowers and seeds.
Differentiate - the one stem cell turns into several stem cells that are different from starting stem cell. The natural phases of progress is from totipotent stem cell to pluripotent stem cells to multipotent stem cells to unipotent stem cells to adult cells, in that order (Bellomo, M. The Stem Cell Divide. 2006). Skin, nose, eyes, blood, liver, heart, bone are organs made of adult cells.
Differentiation is demonstrated in fetal development. The human zygote (one cell, result of fertilization) turns into an embryo that turns into a fetus that turns into a full term; finally a newborn baby.
Differentiation goes on in the body. The lungs take seven years to fully develop. Sexual organs also take several years to develop. Except cardiovascular cells, nerves, and brain cells all other cells in the body undergo apoptosis or programmed cell death. For example, blood cells have a life span of 140 days. Stem cells from the bone morrow differentiate to produce new and replace old blood cells. The natural differentiation is forward.
[There is a fundamental difference between a prokaryotic entity and a eukaryotic entity. The prokaryotic entity does not undergo differentiation. The eukaryotic entity undergoes differentiation.The protozoa, considered as an elementary eukaryote, undergoes differentiation that is why it can assume various forms when it causes malaria.
Sporozoite, the infectious form of protozoa, is transmitted by bites of anopheles mosquitoes. Sporozoite goes to liver, then to red blood cells (to get iron) where it multiplies – one sporozoite differentiates into as many as 40,000 new form called merozoite (McKane, Larry. Ph.D. and Kandel, Judy, Ph.D. M.P.H.1993. Microbiology Essentials and Application). Merozoite goes to the bloodstream and attacks the red blood cells. It differentiates into ring-shaped form called trophozoite that reproduces asexually into thousands upon thousands of merozoites. After several cycles male and female forms appear that are sucked by a mosquito. Inside its stomach the sperm cell fertilizes the egg. Large rounded bodies split into hundreds of sporozoite that pass to the salivary glands of the mosquito (Pelczar, Jr. and R. Reid, Microbiology. 1972:342). The mosquito transmits sporozoites again when it bites a man/woman, dog, or livestock. The female mosquito needs blood to lay eggs. Plasmodium falciparum is the protozoa that causes most cases of malaria in Asia.]
Differentiation is different from cell division like mitosis. Mitosis occurs in a somatic cell, mostly adult cell. For example, one adult cell duplicates itself to give rise into another cell; the subsequent two cells are identical. In differentiation, a totipotent stem cell is not identical to a pluripotent stem cell.
Differentiation is different from meiosis that is a process to reduce the number of chromosomes into half. This occurs in reproductive cells; that is why the sperm has 23 chromosomes and the egg has 23 chromosomes.
Reprogramming of stem cells. Recent stem cell research found that differentiation is amenable to reprogramming. That is, an adult cell can be reprogrammed to revert into pluripotent stem cells. Hubber AliciaC mentions that Sir John Gurdon and Shinya Yamanata succeeded in reprogramming adult stem cells into pluripotent stem cells for which they were awarded the Nobel Prize.
A team lead by Yamanata induced pluripotent stem cells "from human adult fibroblasts;" another team lead by James Thomson's induced skin cells to revert into pluripotent stem cells (Kotantom. Induced pluripotent Stem Cells. Internet. Jan. 15,2013).
There are two important implications of these research findings. One, embryonic stem cell is no longer necessary for use in stem cell research, eschewing ethical issues surrounding it. Two, if an adult cell were needed to be regrown, like an earlobe, adult stem cell like skin could be reprogrammed into a pluripotent stem cell that would trigger body stem cells to differentiate into a new earlobe.
Reprogramming of adult stem cells boosts the power of a theory to be formulated. It opens up the probability of specificity of therapy. If we want to grow an earlobe, it may be more effective to use the adult cell of the earlobe. Reprogramming already provides a tremendous advantage in that growing of pluripotent stem cells can be done with adult cells like skin and blood.
Dr. Arturo V, Estuita, MD, a Filipino internist and chelationist, told me that the latest in stem cell therapy is the oral. Even a small dose of stem cell that is given orally will trigger the pertinent reserve stem cell to differentiate into the adult cell necessary to achieve the integrity of an organism.That means oral stem cell therapy regrows damaged earlobe, or damaged kidney, or damaged heart. His clinic now administers oral stem cell therapy. I have a Hub on how oral stem cell therapy regrows damaged organs.
All concepts and relationships in the hypothesis have been observed. The case of reprogramming of adult cells had been demonstrated.
It would appear that a technology of stem cell therapy has been developed ahead of the formulation of a stem cell-organism theory. That is correct. It was like the case of vaccination that was already being used but its mechanism was not yet understood. It is like the use of nitroglycerin to alleviate angina or chest pain of a victim of heart disease. Nitroglycerin had been long in use but its mechanism was not understood until the medical research done by Robert Futchgott, Ferid Murad and Louis Ignarro. It is like the Salk killed virus polio vaccine. Dr. Jonas Salk and his team had developed this vaccine but no one during their time had formulated a theory that explains how killed virus can vaccinate. (I have a Hub "Salk Vaccine: How the Shape and Size of Killed Poliovirus Incites Immunization").
There had been reports of an earlobe of a human being having been regrown with the use of stem cells. Stem cells found in cord blood is now being used to treat leukemia (Bellomo, M. The Stem Cell Divide. 2006). That is, to grow red blood cells, white blood cells and platelets for use to replace damaged blood cells. Leukemia is uncontrolled growth of white blood cells. An American whose spinal cord had been damaged in an accident has shown recovery after several injections with stem cells into his spinal cord (Supercells, HBO documentary films. Internet. Jan. 14,2013)). Before the application of stem cells, he was paralyzed from the chest down. Now he can move his hands, his feet, and can stand up alone. We interpret these movements as effect of supplied stem cells that induced the differentiation of reserve stem cells. .
If the above concepts and relationships are true and we maintain that they are true, then the hypothesis “A trigger induces the stem cell to differentiate into a multi-celled organism” turns into a theory.
We are fortunate that there are already research results, clinical practice results, cloning in plants and animals (Dolly sheep) that can go into the making of stem cell-organism theory. Einstein was not so fortunate. His special hypothesis of relativity was published in 1905, amplified in 1906 but it was only verified in 1936 first by Enrico Fermi, and confirmed by Lise Mietner, Otto Hahn, von Frisch and company in 1938. So his hypothesis graduated as a theory in 1938 that was further confirmed by the explosion of atomic bombs in 1945. His generalized hypothesis of relativity was published in 1915 that was verified in 1919 by Sir Arthur Eddington (light bends in the vicinity of great body of mass) and in 1929 by Edwin Hubble (the universe is expanding). So this hypothesis graduated as generalized theory of relativity in 1919. The space program is now benefiting from this theory.
The stem cell-organism theory consists of the above proposition, concepts and relationships, together with their definitions, and arguments. Concepts, relationships, evidences and arguments may be amplified further.
You may notice that the proposition is short. It satisfies several criteria in theory-making: it must be short; it contains the least vocabulary; not one of its terms is derived from another. Brevity is guided by Occam's razor, according to Bertrand Russell (Russell, B. Human Knowledge: Its Scope and Limits. 1947). The terms are like survivors from thousands of nymphs of the shrimp or prawn. If two propositions say the same thing one is picked out for being more aesthetic than the other. On vocabulary. for example, the whole of Euclidean geometry can be formulated by means of three terms: point, line, and plane.
We say that this theory holds true for mufti-celled organisms, including human being.
A theory explains and predicts (Campbell, N. What is Science? 1921).
Let’s make a version more friendly to a human being by substituting "human being" for "multi-celled organism," thus:
“A trigger induces stem cell to differentiate into a human being.”
We say that this human being-friendly proposition of the theory explains and that it can predict accurately. That is why it can also serve as a basis of treatment or cure for a human being with a disease involving stem cell
[Treatment is shown by a fellow who has hypertension. When his blood pressure is high, he takes a tranquilizer and his blood pressure goes down. When again provoked into anger his high blood pressure goes up again. His blood pressure was treated. If he goes through chelation therapy and his blood pressure goes down, normalizes and does not recur even when provoked, he is cured.]
That is why we have a therapy that is based on the stem cell-organism theory. So we have what we call stem cell therapy. To repeat, stem cell therapy is an application of the stem cell-organism theory.
This therapy is now being administered as infusion, injection or oral. The Supercells, HBO documentary films, shows one fellow whose heart is afflicted with cardiomyopathy (deterioration of heart muscles due to severe bronchitis). The intention was to treat him of this disease. Stem cells were directly injected into his heart in a hospital in Bangkok, Thailand (see picture). Stem cells propagated from his own blood were used; therefore his body does not reject the stem cells. These will induce stems cells in his heart to differentiate into new heart muscles. Conventional medicine would apply heart transplant, according to the patient who is an American. In fact, his doctors in the US recommended heart transplant..
I have Hubs "The Latest: Oral Stem Cell Therapy Regrows Damaged Earlobe, Heart, Kidney, Liver," and "Chelation and Stem Cell Therapies Completely Repair the Heart."
Stem cell therapy is still considered as experimental. No matter. The theory of stem cell-organism that we have propounded holds. It explains why stem cells from the cord blood can be grown into more stem cells for use as trigger in the production of more blood. An application in therapy is that the cord blood is being used instead of the bone morrow. With this technology, there is no more need to get bone morrow from a donor for use in bone morrow transplants for metastatic cancer.
There is now what we call blood bank where cord blood is being stored cryopreserved in liquid nitrogen. Cord blood of newborn baby can be deposited in a blood bank for use in stem cell therapy. If the owner contracts cancer in adult life his own cord blood can be used to grow more stem cells for his therapy. His body will not reject this stem cell. This cord blood can be used on relatives and probability of rejection will be low.
This theory can be disproved by contrary evidence. For example, a fellow who had been injected with a stem cell of a sheep grew fur. Or a fellow who had ingested fertilized chicken egg grew feathers.
There is a well established therapy based on the stem cell-organism theory. This is chelation therapy for heart disease. Calcium is the cementing agent of the plaque in heart arteries. To dissolve the plaque chelation with EDTA (ethylene-diamine-tetra-acetate) is administered.
During the time that EDTA is circulating in the body, blood calcium is temporarily lowered. This drop stimulates the parathyroid gland to step up production of parathormone. This hormone signals osteoblasts in the bone to increase production of normal bone calcification drawing on calcium sources in the body, like deposits in arterial plaque. When the size of plaque decreases, blood flow increases. Greatest result is often attained in about 90 days. During this period, free radical damage was reduced and gradual cell healing took place (Cranton, E. M.D. 1995. Bypassing Bypass, page 80). Bone calcification involves differentiation. The stem-cell-like endothelium progenitor cell (EPC) from the bone morrow circulating in the blood is responsible for such healing. To recall, no stem cell had not yet been supplied from outside source but insufficiency of calcium served as the trigger.
EPC repairs the inside wall of an artery (Moreno, O.R. et al. “Promoting Mechanisms of Vascular Health.” Journal of the American College of Cardiology. 2009. vol. 53, 25:2315).
If blood with more concentrated stem cells were administered, the healing would be more effective. Blood can be drawn from the patient and grown in artificial medium to produce more concentrated stem cells then injected to the patient. This was done on an American who went to Thailand to have his cardiomyopathy treated.
To prove efficacy, effectiveness and safety of stem cell therapy controlled medical research should be conducted; that is, with the use of appropriate statistical design.. Such research is based on the stem cell-organism theory.
Meanwhile, some people cannot wait for the conduct and results of such controlled medical research. They are willing to take the risks and go through stem cell therapy based on results of clinical practice or anecdotes
Theory-making is different from applied research. For example, in the special hypothesis of relativity involving the formula E = mc2. The first instance of proof was discovered by Enrico Fermi in 1936. The second instance was a verification of Fermi's method and results by Mietner and company in 1938. Then, based on this formula, the atomic bomb was constructed in the Manhattan project. One test bomb was exploded in Alamogordo. The next two atomic bombs were explored in Hiroshima and Nagasaki, Japan in 1945. With only a few verifications of the formula, at least five, made the special hypothesis of relativity to graduate into the special theory of relativity.
Again in the generalized hypothesis of relativity. A verification of one of its predictions, the bending of light in the vicinity of a big mass, by Eddington made it to graduate into the generalized theory of relativity. Another proof was provided by the verification of another of its predictions, the expansion of the universe, derived by Hubble from the red shift.
Applications of the theory of generalized theory further provide evidences. It is now commonplace to launch manned spacecrafts and shuttle buses into space and retrieve them back to earth. The theory requires that the trajectory of splash down is angled 6.2 degrees with respect to the equatorial plane. If it were angled at 45 degrees, the shuttle bus would bounce back to space, the manned spacecraft wound bounce back to space and the astronauts become marooned there. Also, the clock in the spacecraft is slower than the clock on earth. If the two clocks were not adjusted, the spacecraft will land in a crowded city (Hawaii for example) killing a lot of people instead of splashing down in the Pacific ocean.
The one instance of reprogrammed adult cells that induced pluripotent stem cells to progress into multipotent stem cells then into unipotent stem cells is enough to show that adult cells can be reprogrammed. Now, applied research should find out what kind of tissues or organs can be regrown by reprogrammed stem cells. Several instances may be needed that employs statistical significance. That is, 95 instances in 100 cases is statistically significant.
The application of theory would require several instances to achieve a high degree of certainty.
I am undergoing infusion chelation therapy to cure my myocardial ischemia. I have completed 37 sessions out of a prescribed 45 at the clinic of Dr. Estuita. I am getting well, getting stronger as shown by the several Hubs I have posted since I had completed 10 sessions (some light Hubs, others heavy like dealing in theory and philosophy).
I am one more statistical entry in the over 600,000 who had been cured of heart disease with chelation therapy. You may search the Internet with chelation therapy cranton frackelton to read more on chelation therapy.