Genetics:
New Insight into Inheritable Disease and Treatment

Paul Reller, L.Ac.

Many patients, when faced with the seriousness of their health problems, have been led to believe that these health problems are preordained within their genes. This attitude has led to a society that often feels that their only hope is to manage their inherited and preordained health problems with drugs, rather than work on their health and do the many positive therapeutic actions that can correct their problems. A wealth of research in genetics has revealed that our genetic design is not static, but rather a fluid and variable expression that is dependent on many factors that are able to be altered by our choices in life.

A January 2012 issue of National Geographic is devoted to the current science of identical twins and the inherited outcomes of individuals born with exactly the same basic genes. Many of the traits in identical twins, both physical and mental, mature in remarkably similar ways, yet in some cases, the outcomes of genetic expression are radically different. Andrew Feinberg is the director for the Center for Epigenetics at Johns Hopkins School of Medicine. Dr. Feinberg reveals that the question of how our genes will express is not answered in a binary manner, often referred to as “Nature versus Nurture”. Instead, a vast array of variables in genetic expression exist, mostly in the array of molecules that surround the genes, called the epigenome. Dr. Feinberg’s studies reveal that many environmental factors, including diet, medical treatment, physical activity, environmental toxins, and even behavioral and cognitive activities, for example emotional traumas, can alter the expression of our genes, even in the womb. While these genetic expressions often result in astounding developmental similarities in genetically identical twins, the same genetic propensities may be altered by both extrinsic factors and intrinsic biochemical mechanisms. This phenomena is explained to a great extent by the epigenome. Dr. Feinberg has found that epigenetic expression determines how a set genetic code is expressed. Some of these regulating epigenetic expressions follow standard courses, guiding embryonic cells to develop into the necessary array of specialized organ and musculoskeletal cells, while many of them appear to occur randomly, and others as a reaction to environmental factors.

Arturas Petronis, who heads the epigenetic lab at Toronto’s Centre for Addiction and Mental Health, reports that “after 30 years of molecular genetic studies we can explain only about 2 to 3 percent of inherited predisposition to psychiatric disease.” In other words, disease inheritance is much more complex than we assumed, and there will be few simple biochemical corrections that will work to correct our diseases. The complexity of the epigenetic mechanisms that may alter even strongly predisposed disease inheritance suggests that, while genetic predisposition is valid, the patient may do much to alter such predispositions, and the approach should be more complex than just an allopathic single biochemical alteration. In other words, a holistic approach should be taken if one is to successfully alter the course that genetics and epigenetics is taking. The epigenome is largely determined by our choices in life, and is malleable. While these choices are very similar from one individual to another, an evolved sociological order to human life, including a common diet, lifestyle, environment, and even common emotional and spiritual expressions and beliefs, within a culture or civilization, the individual may also take conscious actions to alter these choices. This is the basis for holistic medicine. By changing the diet, consuming herbal chemicals and targeted nutrient chemicals, making cognitive and behavioral changes, and improving or changing one’s environment, the epigenome may be affected, and even genetic propensity to disease altered. Research is even revealing the potential effects of acupuncture stimulation on the expression of the epigenome.

A November 11, 2008 article in the New York Times, Science Times, outlined the current state of research and findings with the enormous push for decoding our genes and discovering cures for many difficult diseases. Unfortunately, the expected discovery of key gene variants that may be altered to cure such diseases as diabetes and cancer has not materialized. A Times article on February 6, 2009, states that most genetic variants found to be associated with common diseases have turned out to account for just 1 percent or so of cases. The search for altered genes has instead found a large number of variants, not a specific genetically inheritable mutation, associated with specific disease. Mother Nature has not confined itself to human systems of classification, and surprisingly, this has surprised researchers. Natural selection seems to correct disease-causing variants before they get common. Our basic genetic code is not ‘set in stone’, but rather constantly mutating, and the array of potential disease-causing genetic mutations are many. The good news is that our organism has evolved a way to constantly correct these disease-causing genetic mutations. The efforts of man-made science pales in relation to this natural system.

One of the very few drugs that actually target a genetic cause of disease was introduced in 2010 and approved by the FDA in 2012. Ivacaftor, or Kalydeco, is a drug developed to treat cystic fibrosis, a disease related to inherited genetic mutations of the gene CFTR, involved in expressing proteins that regulate chloride ion transport across cell membranes. Patients with cystic fibrosis suffer increased lung infections and damage, and a shortened life span. This gene CFTR was identified in 1989, but decades of research was needed to identify the array of mutations that were involved in the disease process. One of the researchers in charge of development at the pharmaceutical manufacturer, Vertex, stated in a February 1, 2012 New York Times article: “There are all these different mutations and each of the mutations was causing it (the gene) to be broken in a different way.” Initial attempts to treat the disease involved putting correct copies of the gene into the patient’s lungs. This did not improve the condition. This drug will help patients with specific mutations, and other drugs are being developed to affect other common mutation. The cost of this drug is $294,000 per year, and will alleviate symptoms for a select subgroup of cystic fibrosis patients, but will likely not reverse years of accumulated lung damage. Such cost is prohibitive for many patients. To affect repair and regrowth of healthy lung tissues while the drug decreases symptoms, the patient and physician may turn to Complementary Medicine and adopt a holistic protocol to help clear diseased tissue and stimulate healthy regrowth. The difficulty and cost of such pharmaceutical treatments has prevented other such drugs to be developed and marketed.

Genetic research has now shifted its focus and reduced its expectations. Researchers now are seeking to find rare genetic variants that might be used to better screen specific portions of the population to identify increased risk of health problems. They also hope to uncover more specific data on disease mechanisms as they study these rare genetic variants that the human organism has not yet cleaned up with natural homeostatic processes. A June 6, 2010, article in the New York Times sums up the current research finding and dissapointments: http://www.nytimes.com/2010/06/13/health/research/13genome.html. The problems faced in utilizing this now vast knowledge of the human genome are great. If the array of diseases we face are connected to individualized genetic variants that are relatively rare, each individual would have to have their complete genome mapped and studied. This is increasingly available to individuals, but still costs about $5-10,000, which would not include the actual computerized analysis of the genetic variants in relation to a number of genetic mechanisms that would need to be addressed for each individual. Currently, analysis of the genome in a large study by Brigham and Women's Hospital in Boston, in relation to women and cardiovascular disease, proved to have little or no value in predicting cardiovascular disease over 12 years in 19,000 women studied. While modern medicine has convinced the public that genetic research holds astounding promise to finally cure or prevent their diseases, this is not proving true.

The human genome has been mapped. This genome research has led to the possibility that we will find no specific cures within single genes. Our understanding of the very nature of our genetic material has changed with these findings, though, as research has expanded. We now know that DNA is not composed of genes, or segments, that contain the blueprints for specific proteins. Instead, a single section of DNA that we have called a gene can make more than one protein to regulate our physiology, and is dependant on a complex surrounding epigenome to guide its function and expression. To fully utilize our new knowledge of genetics, we must now develop a holistic, or quantum mechanical view of genetics and disease inheritance, and this points to a future that combines biotech drugs with holistic medicine to achieve broader, systemic and coordinated effects in our bodies. To further this understanding, the National Institutes of Health (NIH) has created the Roadmap Epigenomics Program, begun in 2008 at more than 40 labs. The findings of this epigenetic mapping will most assuredly point to a complex and variable array of factors and treatments that may alter the course of an individual disease, or prevent it.

The concept of a gene may now incorporate not just the specific stretch of DNA that we have used to define the gene in the past, but also the exons, or RNA expression, from other genes that affect the genetic expression, as well as the epigenetic marks from surrounding molecules and chemicals that are not static. In fact, given the amazing rate of genetic mutation and correction in the organism, none of our genetics is particularly static. The gene is now a fluid abstract entity in science, similar in concept to some of the fluid abstract concepts in Traditional Chinese Medicine, such as Qi, Yin and Yang. These abstract concepts of our physiology, devised thousands of years ago by physicians that were devoted to a natural science called Taoism, perfectly express the ever changing, but homeostatically balanced nature of our genetic inheritance. Our notion of inherited disease and disorder also becomes more fluid and malleable with this change of knowledge. Already, most of us are aware that we may have inherited propensity to a disease, rather than certainty of the disease, and now this concept is expanded. In terms of our health, this means that there may be a number of things we can do to alter the risk of the genetic expression of disease. Complementary Medicine offers the chance to affect this aspect of our health in a varied and complex holistic manner.

Where has all of our efforts to map the human genome and discover the precise origins of inherited disease led to? Let us look at just one example. The National Human Genome Research Institute (NHGRI), part of the National Institute of Health (NIH), published a report in the March 31, 2008 issue of Nature Genetics that states that 16 genetic risk factors associated with diabetes have already been discovered, with more expected. In other words, there is no promised single genetic cause for this disease that can lead to an effective allopathic cure. The number of genetic variants potentially associated with disease discovered in total with current research is phenomenal. It appears that new genetic variants are being created constantly, most of which are corrected with a variety of processes that lead some scientists to conclude that we may never fully understand our genetic mechanisms, even after mapping the human genome. The implications of this new understanding is that we must focus on restoring proper homeostatic function to the body, as a whole entity, to actually succeed with specific chemical manipulation to counteract disease mechanisms. The promise of biotech is there, but may not be particularly effective if the whole health of the patient is not addressed. There will always be so many variables affecting genetic expression that single bioengineered chemicals will need help, both in achieving proper effects, and in alleviating unwanted affects of altering or blocking genetic expression. This help will come in the form of integrated Complementary Medicine and the holistic medical approach.

Understanding the Role of Genes, DNA, RNA and the Epigenome

Mapping the human genome has accomplished a recognition of only about one percent of the entire DNA structure of our genetic code, and the project to map the other 99 percent, ENCODE, has discovered that even this one percent of protein-encoding genes that we consider our basic genetic code averages 5.7 different protein transcripts per bit of DNA, and incorporates RNA exons, or genetic transcripts, from distant locations on the genome, even from different chromosomes. In other words, even our basic genes multitask, and to affect a single genetic expression of regulating proteins, we would have to also account for an array of contributing genetic expressions on other parts of our basic chromosome. We can no longer think of genes as being single stretches of DNA at one physical location, and the implication of this in terms of allopathic correction of human disease is enormous. The path of our biotech direction has been altered in medical science.

Up to this point in time, a gene was considered an almost absolute determinant of inheritable traits, which worked by carrying the segment of bases, or building blocks, that coded specific proteins which regulated functions in all of our cells. Two camps, the “Nature versus Nurture” parties, similar to our political parties, have achieved gridlock rather than progress. The process of disease determination was thought to be carried out by the DNA regulation of single strands of the genetic code, called RNA, which are a small segment of the sequential base code. The basic human genome contains more than 3 billion of these sequential bases, and a very small part of these DNA sequences make up exons, which are the RNA sequences that the chromosome uses to make a specific protein. Although these protein expressing RNA strands make up less than 2% of our RNA, we assumed that the rest was non-expressing DNA. We now know that much of this DNA, commonly called junk DNA, actually expresses proteins and carries out a variety of regulatory mechanisms beside protein regulation, with the assistance of the molecules surrounding the gene, or the eipgenome.

The molecules that make up the sequences that define DNA are called base pairs. A base pair, on opposite strands of DNA, is made of nucleotides, which are simple carbon rings with oxygen, nitrogen and a phosphate group attached. Five simple variations form the most common purine and pyrimidine nucleotides. Human chromosomes are single, very long DNA strands, found in each of our cells, and we have identified 23 pairs, or 46 chromosomes, 2 of which are identified with our sexual classification. It was assumed that these chromosomes were the complete determinants of our hereditary traits. Abnormalities of the chromosome were strongly linked to certain inherited conditions, such as Down's Syndrome, and so it was assumed that chromosome mutations were responsible for a large number of diseases, especially those with apparently inherited frequency. We now know that the subject of inherited disease traits is a much more complicated subject.

How complex is the task of curing disease by chemicals that block genetic expression, or even stem cell replacement? It was thought that a single chromosome may contain over 4000 genes, and nearly a quarter of a million sequenced bases. It seems that we may have underestimated even this complexity. In 2003, the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, found that the Y chromosome harbors up to 3 times the number of genes than previously attributed. The 3 million base pair strands were found to be palindromes, reading the same backward as forward. This may be a unique way for this easily mutating chromosome to constantly repair itself. The cell may utilize the palindromic long strands to constantly restore the chromosome to a normal sequence, and thus repair the DNA, which is constantly mutating. This complexity of constant DNA chromosome mutations and repair poses a significant problem in the discovery of specific chemical treatments for genetic-based medicine, as well as the use of stem cell material. Diseases related to dysfunction of this complex mutation and repair mechanism may be better addressed by including therapies aimed at restoring proper biochemical function, especially in immune enhancement, but also in relation to other biochemical processes that are affected by nutrient chemicals and acupuncture stimulation. Curing, preventing or alleviating disease mechanisms related to rare genetic variants might be best accomplished by encouraging natural homeostatic mechanisms that our bodies have developed over millions of years of evolution. This is where Complementary Medicine and TCM play a significant role.

Epigenetics is a word that describes the chemical physiology surrounding our genes that alters the genetic mechanism. Recent studies show that both industrial and environnmental chemicals, as well as common nutrient changes, may alter the epigenetic patterns that affect inheritable disorders. The genes themselve do not need to be mutated to affect the inheritance of disease risk and health problems. Our DNA is surrounded by many proteins and other molecules that modulate genetic expression, such as carbon and hydrogen methyl groups that cap our DNA, and protein histones that determine the ability to express. In embryonic development, this epigenome appears to be stripped away and a fresh set of epigenomic marks are developed in the same pattern as the parents. If the embryo is exposed to particular toxins or nutritional deficiencies, it may develop a problem with the new epigenome. If the parents alter their epigenome with some exposure to toxin, this new epigenomic trait may be passed on for a few generations. This was proven in a study by Matthew Amvway at Washington State University that showed that epigenetic traits in laboratory animals could be induced by industrial chemical exposure and carry on through 3 generations.

Nutrigenomics describes changes that dietary patterns have made o the epigenome while not directly affecting the gene itself. A USDA-ARS 2008 study by C J Li, T H Elsasser and R W Li of the Bovine Functional Genomics Laboratory showed that ruminant species have changed their nutrient intake and evolved greater metabolism of short chain fatty acids, such as butyrate, that have significantly altered the gene expressions that regulate cell growth, immune respose and signal transduction. Further study is sure to illuminate more detailed changes in nutrient intake that could affect our health both negatively and positively.

What is revealed in this type of study is that herbal chemicals and nutrient supplements do play a potential role in epigenetic treatment protocol. A published study by the NIEHS (National Institute of Environmental Health Services), entitled Biological Response Indicators of Environmental Stress (RFA 06-013) stated: "Another example relates to the assessment of gene-specific and global epigenetic changes influence by dietary exposures. A recent study showed that supplementation with folic acid, vitamin B12, choline, and betaine altered gene phenotype in agouti(A(vy)) mice through increased DNA methylation at the A(vy) locus. Beginning with animal studies, the effects of dietary supplementation with folic acid and other B vitamins could be assessed with respect to gene-specific epigenetic changes (e.g. alterations in imprinted genes, including IGF2 and CDKINIC), global methylation changes, or histone modification changes." The potential for phytochemical and nutriceutical effects on epigenetic disease processes to accompany specific pharmaceutical approaches is very real and close at hand.

Implications of side effects from new pharmaceutical manipulation of genetic expression, and the potential to alleviate side effects with Complementary Medicine

RNA interference, or RNAi, is a relatively new protocol for blocking disease mechanisms by downregulating genetic expression. Bioengineers believe that all of our genes can be downregulated as regards protein expression by RNAi, and newer drugs will be able to decrease specific protein formation to alter disease metabolism. Unfortunately, the full effect of these drugs won't be fully understood for some time. Blocking RNA expression at one point on our huge genome will probably not be accomplished without altering either protein expression at another point, or altering the chain of events associated with that protein expression in the complicated feedback mechanisms of our epigenome. As discovered, a single gene may express not just one, but a number of proteins, and each gene may be effected by other genes as well as the epigenome. Side effects may be a significant drawback to such therapy. In cases where the beneficial outcome outweighs the risk of side effects, Complementary Medicine could provide the means to decrease risk of side effects so that the patient is more comfortable with the treatment.

"The key to a comprehensive health care protocol for the future involves greater utilization of Complementary Medicine to decrease risk, alleviate side effects, and enhance effectiveness of new drug protocols."

Traditional Chinese Medicine has a long history of addressing the health of the genetic and epigenetic regulation of the body. The word for this in TCM is Jing, which refers to the fundamental substance which maintains the functioning of the body. A variety of treatment strategies, both in acupuncture, and in herbal medicine, are used to strengthen this essential substance and function. TCM has always viewed the genetic makeup as a complex system that is holistically functional and constantly in flux, transforming and correcting itself continuously. In this way, the ancient physicians of China anticipated what modern scientists are now discovering, the quantum mechanics of our essential biological being.

The role of viral infection in altering and evolving our genetic makeup, and the implications for healthcare protocol

One of the most amazing books ever published is title Microcosmos, Four Billion Years of Microbial Evolution, by Dorian Sagan and Lynn Margulis. This book clearly outlines the known mechanisms of genetic evolution, including the role of viruses, which in fact are just bits of RNA and DNA that are encapsulated. Current genetic research has discovered a massive amount of viral DNA still incorporated into our genetic structure from millions of years of infection by different viruses. This viral DNA has become a quantitatively dominant part of our genome, and even old viral DNA may still copy itself and this copy may move to another part of our genome, where it may disrupt protein expression, or even create proteins, some of which are known to have beneficial effects. These viruses are actually a key component to our survival, creating genetic innovation that our bodies can use to counter evolving threats to our biological survival.

The most amazing thing that we have discovered about viruses is that these unliving bits of DNA and RNA themselves are in a costant state of evolution and change. They evolve differently than living organisms, though. It is found that viruses evolve not through generations of inherited changes, but horizontally in time, with types of viral material in our world apparently changing simultaneously. This accounts for the simultaneous outbreaks of certain viral endemics around the world, such as the 1918 avian flu, which perhaps killed over 20 million people and ended World War I. This outbreak occurred in the same week in many locations over the entire globe.

Protection against some of the most dangerous viruses could affect the risk of disease occurrence and the potential passing of epigenetic inheritance to our offspring. The safest method of countering the ill effects of viral illness is to help the body in its complex response to viruses. This is how Complementary Medicine works. Acupuncture and herbal medicine seeks to increase the efficiency of the immune system in its proper and evolved role in insuring that the viruses we encounter do not cause more damage than our bodies want. Many diseases, including most autoimmune disorders, are thought to be caused by the unwanted incorporation of viruses into our genetic structure and subsequent expression. This is a very complex process, and allopathic medicine may never offer a workable response to this disease mechanism because of its inherent specificity. Holistic medicine offers a number of means of improving the health of the immune system and providing antiviral chemicals that have evolved within plants.

What is the safety level of these herbs and cures?

To date, there has been no claims of health injury of consequence from the proper prescription of these natural cures, and acupuncture stimulation remains the safest treatment in human history, with virtually no complaints of injury in the United States other than a few cases of minor bruising or skin reaction. The malpractice cost to a practitioner of TCM is approximately one thousand dollars a year, reflecting the fact that there are no lawsuits. The TCM physician completes a graduate degree from a specialized medical school that requires much knowledge of medicine, modern and traditional, and usually includes extensive study in herbal medicine.

As progress is made in the research and clinical use of herbal medicines and acupuncture to regulate the body, many more specific uses of herbs will be uncovered. The body of knowledge grows every day. What is important is that you take products with reliable quality and the proper dose. This is accomplished by choosing a TCM physician with the knowledge and clinical experience to utilize quality herbal products and supplements and perform and coordinate care in a professional manner. The quality of products varies considerably and dosage claims are often false in a business that has no government regulation. It pays to utilize a professional to guide your care rather than to rely on self medication.

Information Resources

One example of the research exploring the effects of Traditional Chinese Medicine, or Chinese herbal chemistry, on the epigenome, is shown here: http://www.hindawi.com/journals/ecam/2011/816714/