Elucidation of DNA structure as right handed double helix by Watson and Crick in 1953, who were awarded Nobel Prize in 1962, was a mile stone in the era of modern biology.  Human Genome Project was conceived in 1984, started in 1990 and completed in 2003.  Two teams were involved namely

1.         International Human Genome Sequencing consortium (IHGSC) headed by Francis Collins involving research groups from USA, UK, France, Germany, Japan and China and

2.          Celera Genomics - private company at Maryland led by Craig Venter. Human Genome has 3 billion base pairs with 34000 genes coding for proteins (less than 3% of total DNA).  More than 97% of DNA is non coding (so called Junk DNA) involved in regulating gene expression during development, differentiation and adaptation to environment.

                   Gene is DNA, carries genetic information from one cell to the offspring.  It determines morphological, chemical and metabolic characteristics of individual cell or organism.  Mammalian cell possesses about 1000 times more genetic information than does the bacterium E. coli. Humans have same DNA to the extent of 99.9%. Fraction of a percent gives individuality (intelligent, dullard, aggressive, mild, normal, disabled etc.).  Further Humans share 98% DNA sequence with monkeys, 57% with cabbage.  Only 300 genes of humans had no recognisable counter part in the mouse. Humble weed plant, Thale cross (Arabidopsis thaliana) carries 30% of its genes with notable similarities to humans.  The commonness of some genes shows subtle connection between all living systems.

            After decoding Human Genome, there is considerable awareness and expectation in the public.   It is not a surprise to see the scientists, scientific journals and magazines with sensational news on Genes.  Geneticists, Psychologists, Psychoneuroendocrinologists are excited and actively involved in Genomic Research. Number of Genes associating with behaviour, emotions and feelings have been often reported.  To name a few Gene NeuroD2 with dare devil behaviour, CYP2A6 with addiction, ISIG2 with obesity, DRD4 with sexual desire & performance, Variants of DRD2 with anorexia, AVPRIA and SLC6A4 with creative / dance performance.  God Gene - VMAT2 with human spirituality, GCH1 with chronic pain, TREK – 1 with happiness, BDNF with depression,  gpr 54 with puberty, and 10 Genetic mutations in SIR3, SIRT1, IGF - 1, Lamin A (Pr) etc with longevity (life span).  Presence of a particular Gene is not sufficient.  Its expression is important.  Genes may be Constitutive Genes (house keeping genes) for synthesis of proteins required for the cell, expressed at more or less constant rate in all the cells.  Some genes are regulated (induction or repression) by various molecular signals.

            Gene Regulation in Eukaryotes is more complicated and is brought out by several mechanisms like gene amplification, gene rearrangement (light chain and heavy chain Ig), small RNAs as enhancers / silencers and deacetylation of histone protein, methylation of DNA in inactivation of genes.

            Although > 99% of human DNA sequences are the same across the population, difference between individuals are largely due to SNPs (Single Nucleotide Polymorphisms). About 3 million SNPs are believed to be present in the Genome.  It involves the replacement of one nitrogen base by another (C→T or A→G etc).  Sickle cell anemia is due to a single nucleotide change (A→T) in the β-globin gene of hemoglobin. SNP maps of human genome can help in determining the likelihood of some one developing a particular disease (cancer, diabetes etc.).  SNP map project is of interest in pharmocogenomic studies (effect of drugs in individuals) and hence number of drug companies have funded to find new SNPs. Studies at University of Pennsylvania on Gene activity of 4197 genes in white cell lymphoblostoid, showed Europeans and Chinese expressed 939 at significantly different levels while Europeans and Japanese expressing 756 differently.  This is due to SNPs showing how tiny changes in the basic DNA code can significantly affect the expression of whole genes.   Populations that differ in their susceptibility to diseases such as type 2 diabetes and high BP carry different SNPs and the specific genes may be targeted with drugs.  Gene sequences alone do not tell the whole story.  Svante Pääbo (Director of Evolutionary Genetics, Germany) observed differences in gene expression by measuring mRNA in autopsied brains, possibly playing a role in creating the gap between the chimp and human brains.  Pääbo recently began a project to breed mice laced with human – specific genes involved with brain growth and development.  The first of these humanized mice are now being born in Germany (Discover Dec, 2006).

            Epigenetics is the Study of heritable changes in gene function that occur without a change in the DNA sequence.  Epigenetic mechanisms such as DNA methylation, histone acetylation, RNA interference, Gene imprinting and silencing play important role in gene activation and inactivation and in phenotype transmission and development, the so called epigenetic inheritance.   A simple environmental effect could switch genes on or off – and this change could be inherited. The idea that inheritance is not just about which genes you inherit but whether these are switched on or off is a whole new frontier in Biology. Genes and the environment are not mutually exclusive but are inextricably interwined, one affecting the other.  ‘Incorrect’ epigenetic changes to tumor suppressor genes and oncogenes are some of the first steps in cancer initiation.  Studies at Mount Sinai School of Medicine on the effect of stress on pregnant women who were inside or near the World Trade Center during tragic events on September 11, 2001 suggest that stress effects can pass down generations.  Another study at Washington State University points to toxic effects, causing biological changes in rats exposed to pesticides persist for at least four generations. 

            Different studies brought a paradigm shift in scientific thinking how life style and family relationships affect individuals and also their children and grand children in decades to come.  If you liken the genome to the hardware of a computer, the epigenetics is the software. There are number of research studies using Holistic Medicine for prevention and management of cancer.  Studies at McGill University showed that nutrients and supplements changed genetics by switching on or off certain genes in rodents.  L-methionine, a common amino acid and food supplement, when injected into the brains, the amino acid methylated the glucocorticoid gene, and the animal’s behaviour changed.  Green tea helps in silencing HER-2 genes that fuels breast cancer in some women. Turmeric suppresses genes (COX-2) that ratchet up inflammation.   Nutrition and Genetics is catching up.  Within a decade, doctors will be able to take genetic profiles of their patients, identify specific diseases for which they are at risk and create customized nutrition plans accordingly.

             Nature Vs Nurture has been debated often.  DNA is not destiny.  “Gene as fate” has been conventional wisdom.  Through the study of epigenetics, that notion may be proved outdated. Unlike genetic mutations, epigenetic changes are potentially reversible by switch on and off mechanisms (methylation or demethylation).  One epigenetic drug, 5-azacytidine has been approved by FDA for treating myelodysplastic syndrome (pre leukemia). Similarly studies on development of drugs for other cancers are under testing.

            Epigenetics introduces the concept of ‘free will’ into our idea of genetics.  Epigenome can change in response to the environment through out an individual’s lifetime.  Now everything we do – everything we eat or smoke can affect our gene expression and that of future generations. The environment (diet, behaviour, family relationship, lifestyle and surroundings) has a role to play in changing our genome, bridging the gap between social processes and biological processes.

            In this scenario definition of Holistic Living in the recent Symposium held at Sevagram may be of interest. Holistic Living is defined as Simple, spiritual, purposeful, peaceful and productive living with moderation in food intake, adequate exercise and positive thinking and attitude to life.  Holistic Living is an art of living in harmony with nature and concern to the whole universe.

Prof. B. C. Harinath

March 15, 2007    

The rejection of two bills by Senate committee of US State of New Mexico, demanding a ban on the use of aspartame, an artificial sweetener in food items which is said to increase the risk of cancer, is revealing and exposes the strong hold of Food Industry on the law makers.  The simple reason for rejection was that about 6000 food products such as cough syrups, chewing gum, candy, desserts, soft drinks etc. contain aspartame and the bills would be an invitation to commercial chaos (Down to Earth, April 15, 2007).  A study by researchers from Cesare Maltoni Cancer Research Centre in Italy, showed that the Aspartame (a dipeptide of aspartic acid and a methyl ester of phenyl alaniney, produced by Mon Santo) can cause cancer on rats at levels approved for human consumption (Down to Earth, December 31, 2005).  As expected, the industry contested the results and the way the study was conducted.  Public witnessed similar drama before banning carcinogenic Cyclamate, a sugar substitute used in the food beverages in the past.  Morando Soffritti, Scientific Director of Ramazzini Foundation (Italy) sticked to his research results and agreed to share with regulatory bodies which plan to reassess aspartame’s safety. Other non-caloric artificial sweeteners namely Sucralose (a chlorinated sucrose derivative) under the brand name Splenda (Patented by Johnson and Johnson) has entered Indian market.  Soft drink manufactures have decided to use Splenda in their diet drinks.  Doubts are being raised on its safety and long term use may contribute to serious chronic immunological or neurological disorders. (www.sweetpoison.com) The sane advice is to avoid use of chemical artificial sweeteners in the interest of one’s own health.

            The story of artificial sweeteners opens up the Pandora’s box on junk foods causing the problems of obesity, diabetes, asthma and other health problems. The consumption of junk food places a greater burden on health care systems than Natural and Healthy food.  Doctors at Belfast BMA meeting recommended that Food manufacturers should be forced by law to adopt a “traffic light” system to signal nutritional content of food products, green symbol to indicate healthy and red symbol for foods in which most ingredients are not nutritious meaning that this food should be eaten only occasionally.  A report from US Institute of Medicine says that Junk food and the advertising that promotes it are serious threats to health of young Americans.  The Australian Divisions of General Practice, whose research found 99% television food commercials during children’s viewing periods were for sweets and soft drinks.  Australian Government threatens tighter regulation on junk food advertising.  The European commission is stepping pressure on the food industry to phase out junk food advertisements targeted at children to reverse the growing trend of obesity among young people. The European Union approved legislation on food labeling to set new standards for the claims that food manufacturers make about their products i.e. use of false or misleading terms such as “fat free”, “high fibre” or “low alcohol” etc.

            The first lawyer to sue the tobacco industry, Professor John Banzhaf is predicting a series of similar suits against the fast food industry for its role in the obesity epidemic. Eric Schlosser in his book ‘Fast food Nation’ accuses the Fast Food Industry of many things: advertising to children and playing a leading role in the Nation’s obesity epidemic.  He portrays how US as a Nation radically altered economic and social policies to accommodate the manufacture and consumption of fast food.  He writes that Americans spend more on fast food than on movies, books, magazines, newspapers and music – combined.  In 1970, Americans spent about $ 6 billion on fast food; in 2000, they spent more than $ 110 billion.

            Prof. Philip James has been driving force behind Britain’s Food Standards Agency, has been convinced that something “very dramatic and different” had to be done to strengthen the weak links in the Food Chain.  There is urgent need for food safety: from plough to plate which involves industry farming, synthetic fertilizers, pesticides, food processing using various chemicals to present food more attractive and addictive for increasing consumption and make profit.  Lobbies of industries succeeded in making State legislatures to enact “Common Sense Consumption” law to discourage litigation.

            There is a feeling in the public that ministers, producers and retailers are patronizing, misleading and stemming more from a desire to protect profits than to protect the public health (www.bmj.com). Adding salt to injury, a study suggests spread of multidrug-resistant Salmonella enterica Schwarzengrund from chicken meat to persons in Thailand and from imported Thai food products to persons in Denmark and the United States (Emerging Infectious Diseases, May 2007).  Indeed, true globalization of spreading diseases through food products. Future of food appears to be more challenging and fearful with introduction of genetically modified foods claiming the power to improve health, prevent disease, delay senility, boosting our mood etc. (The Future of Food by Brain J.Ford)

            Let us learn from advanced countries on the pitfalls of management of Food industry, and make ‘food’ labour intensive service and cottage industry, keeping away from MNCS.  Let us make and present food natural, fresh and homely, for human health is more precious than economic gain.  Good and tasty food does not need advertisement.

Prof. B. C. Harinath

June 15, 2007

    Americans are not only rich but fatty too, with obesity rates ranged from more than 17% in Colorado to more than 30% in Mississippi. Rate of adult obesity now exceed 25% in 19 states. The rate of childhood obesity more than tripled from 1980 to 2004 with approximately 25 million children are now either obese or overweight. Childhood obesity is showing increasing trend in developing countries with growing economy, thanks to fast food and beverage companies.

          Obesity is a symbol of unethical consumerism aggressively pursued by processed food industry aimed at growing company's profits with least concern to human health. The weak and poor become prey to obesity and whole society has to pay for it. It is very clear that not only calories but chemicals as well are the culprits causing obesity and affecting health. Metabolic Syndrome, a cluster of symptoms and signs that represent a step on the path towards diabetes. Raising of health care costs due to the chronic health problems such as Diabetes Mellitus, high blood pressure, heart disease etc. associated with obesity is going to cripple New Zealand's health system, the government fears. Global war on fast foods and changes in life style are inevitable for reducing healthcare costs and maintain better health.

        Eating too much and lack of exercise are not only the reasons for people gaining weight, genetics, metabolism and environmental factors do explain how large your appetite is and how efficiently your body uses the food you eat.

         Obesity has given rise to Nutrigenomics, a science of health and balanced diet and tells how food influences turn on / off genes associated with weight gain or loss. Management of obesity has become a business with diet plans, books on losing weight and being healthy, gastric bypass surgery, steroids and other anti-obesity drugs (Xenical blocking absorption of fat, Rimonabant blocking cannabinoid receptors with serious side-effects).

        Studies show there are genetic links to obesity, thus obesity is hereditary and is acquired. Review of genetic data by DNA Micro array analysis on more than 38,000 children and adults in UK & Europe showed certain variations in the FTO gene was associated with extra body fat, obesity and Type II diabetes. About 56 genes have been linked to obesity in rodents but 10 are accepted widely as having any influence in humans. Most explored are concerned with the hormones ghrelin, which stimulates appetite and leptin, which helps regulate fat storage in the body.

        The anti-obesity groups such as 'Fight the Obesity Epidemic (FOE)', 'Obesity Action Coalition (OAC)', 'Trust for America's Health', advocate a concerted effort to fight obesity by banning or strongly regulating advertisements and decreasing consumption of fast foods by children, a difficult proposition which is resisted by Food & Beverage Industry and Grocery Manufacturers Association.

         Prof. Banzhaf (www.banzhaf.net) has been in the news about using legal action against the problem of obesity in some of the same ways he pioneered against the problem of smoking. So far, number of FAT lawsuits against growing epidemic of obesity have been successful against McDonald's French fries, Big Daddy's Diet ice-cream, Pirate's Booty diet food, Kraft's Oreo cookies, McDonald's & KFC's Transfat, Nation's bottler's sugary soft drinks in schools, paying millions of dollars to Plaintiffs by the Food & Beverage companies for misrepresenting facts on the food labels and misguiding consumers.