Conclusion of the human genome project also marked the beginning of a plethora of data mining activity worldwide. The implication of this project in medical science was overwhelming and so was the enthusiasm to excavate more from this vast data base. The historical declaration by then US President Mr. Bill Clinton that human genome sequence cannot be patented might have sent the Celera stock plummeting down but it marked the beginning of the spirit of sharing human genome information with all around the world. The American researcher Dr. Craig Ventor’s privately funded human genome mapping project that ran in parallel to the similar project led by the US government also added to the wealth of information now available in the public domain.
The eagerness to acquire propriety rights over human genome information by multinational stalwarts was for reasons little more than mere possessiveness towards a meritoriously generated set of data. It was a clear vision of the future implication of this information in ameliorating human health conditions by studying genes and their purposes as well as subsequent, almost endless, business prospects. Credit goes to decisive dictate by the nations of the world, may it be the historical 1996 Bermuda statement or Mr. Bill Clinton’s declaration to keep knowledge free for access because of which human genome mapping information and human genome data, though created by a handful of stalwart biological researchers and genome enthusiasts, still remains for the entire scientific community to read, understand and explore.
Medical research has ironically not changed much since the days when Edward Jenner discovering the first vaccine concept and Selman Waksman coined the word ‘antibiotic’, to usher one of the most landmark discoveries in medical history. But the world still revolves around the principle of prevention and cure, both encouraged and bolstered by a third assisting dimension called the ‘diagnostics’.
‘Prevention’ as a concept however underwent logical evolution until biochemistry made leads in medical research and so did knowledge in the domain of human physiology. It no longer relies in its entirety over vaccination but talks about ‘supplements’, ‘diet management’ ‘lifestyle changes’ and such other various expanding healthcare parameters.
However, with the advent of the new stream of human genetics that become increasing important in medical science, there is now a surge of interest as well as information in understanding the role of genes in human health. Since the days of George Beadle (Cal Tech, USA) & Edward Tatum (Rockefeller Institute) who then encouraged the concept of one defective gene coding for one defective enzyme leading to one disease (one gene one enzyme hypothesis), the world now faces the stark reality of lifestyle diseases, least bestowed with the simplicity of a single gene causing them and instead find their cause in multiple genes interacting with environment in the most complex manner to cause diseases such as diabetes type II and osteoporosis. Academic faculties such as Epigenetics were created to understand this complex gene-environment interaction phenomenon that still remains a potential enigma to the entire research community.
Over 30 million people have now been diagnosed with diabetes in India. The CPR (Crude prevalence rate) in the urban areas of India is thought to be nine per cent. In rural areas, the prevalence is approximately three per cent of the total population. The population of India is now more than 1000 million: this helps to give an idea of the scale of the problem. The estimate of the actual number of diabetics in India is around 40 million. These statistics indicate the attention this disease deserves coupled with the fact that it is not blessed with attributes of a vaccine-based prevention (for obvious reasons) and is left to the mercy of drugs that dance to the tune of ‘pharmacogenomic predisposition’ of a certain individual. In short, prevention is not so straight forward and neither is drug-efficacy uniform in all instances.
The world therefore is rising up to the knocks of ‘pharmacogenomics’ and ‘genetic predisposition’, it wants them or not, to rein the disease that otherwise is destined to ruin the population if left uncontrolled. Life is a three letter word, DNA. Though little overemphasized, this casual statement possibly meant that much of life’s mysteries revolve around the genetic material, DNA. Few of my literature enthusiast friends went to solve the complex queries of Hindu religious scripts indicating that indeed ‘DNA’ is what it meant by the true ‘Brahmin’ or the all knower of truth as it codes for the entire life in a single package of chromosomes. I however prefer to remain modest identifying DNA as the unique molecule responsible for a vast segment of human health and emotional conditions.
Genome analysis has revealed important information. It is now able to guide us in understanding the complex pathway that when tickled cause a certain disease. Given the fact that all pathways are controlled by enzymes which in turn are coded by genes, a defect in gene architecture has adverse effect on health that causes a disease. In this context, lifestyle diseases such as diabetes take a special position. Well being of an individual is contributed both by the genetic structure as well as environment. A ‘good’ genetic background of an individual coupled with a ‘good’ environment (read life style) is believed to keep at bay diseases such as diabetes type II. However, a bad genetic background coupled with a ‘good’ lifestyle fails to score enough ‘healthy’ points and in such cases, additional efforts are required to make good the deficiencies placed by the poor genetic makeup. The genetic get-up of an individual is destined the day his/her embryo is born and thereafter is unchangeable. This of course does not count the recent strides in human ‘gene therapy’ that is yet to make a mark in the society. However, lifestyle, comprising of dietary habits and exercise can always be changed and modulated to complement the genetic deficiencies such that onset of such diseases can be deferred or denied. This might even be a more routine surveillance of one’s health conditions for a pick of the early signals of onset of the disease. This timely intervention is believed to be the biggest gift of such genetic knowledge made available to the society. The harsh reality of diabetes with its debilitating effect on nerves (neuropathy), heart and quality of life is more fearing than undertaking a small genetic test followed by suitable surveillance and lifestyle modifications. This is where predictive genetics comes into play.
Biochemistry has done its bit. Rapid blood glucose test is available and so is the method for estimating average plasma glucose concentration in the blood (HbA1c test). However, they are essentially for people who are diagnosed of diabetes, a stage that can be deferred with lifestyle modifications.
One of the classic differences between a conventional medical test and that of a predictive genetic test is that the latter is done on normal individuals. This is for obvious reason since action based on prediction can be taken only when the disease stage has not arrived. In diabetes, several important genes have been indicated for their role in causing the disease. For example, vitamin D receptor gene is responsible for mechanism of insulin secretion, interleukin 6 and tumor necrosis alpha genes are responsible for inflammatory response and response of cells to insulin and TCF7L2 gene too is intimately involved in modulating the mechanism of insulin secretion. Mutation in these genes therefore is destined to have adverse effect on the general pathway of glucose absorption and utilization by cells.
Humans have, unlike microbes, two copies of each gene. This complicates the scenario by raising situations where one gene is mutated while the other is not (a condition known as heterozygous) compared to those where either both genes and none are mutated (a condition known as homozygous). Accurate identification of such mutation profile helps in predicting the subsequent genetic predisposition of an individual to the disease and assists in advising preventive lifestyle and associated changes such that the onset of disease can be deferred or denied. This is coupled with all other advantages linked to taking positive control of one’s life when his/her own genetic background is known in advance.
Since the day when James Watson and Francis Crick first announced to patrons in a Cambridge pub that they had just discovered the secret of life, time has changed seeing enormous strides in evolution of methods and tools for analyzing DNA. The days of 1970s saw the first DNA sequences getting obtained by laborious 2-dimensional chromatography techniques. In 1976–1977, Allan Maxim and Walter Gilbert developed an ‘art’ of DNA sequencing based on chemical modification of DNA and subsequent cleavage at specific bases. This method was subsequently refined to automation platforms that later became the workhorse for human genome sequencing project. This is also the ‘often-used’ tool for discovering and identifying gene mutations.
geneOmbio technologies is one of the first organizations in India to provide predictive genetic test for two major life style diseases, namely diabetes type II and osteoporosis. For this it uses state of the art, automated, fluorescent DNA sequencing platform to identify well-studied gene mutations that are linked to efficacy of the genes in question. It concludes the report indicating the score a person accrues due to his genes (higher the worse) that is turn is appended with lifestyle measure related advices from trained professional.
India needs a rapid sea change in thinking about its health particularly when it is healthy. This new class of tests with its peculiarity of being applicable only on asymptomatic people in itself is a fundamental jerk to the diagnostic psyche of our society which is tuned to a test recommendation when conditions of illness prevail. This, coupled with the fact that it eventually does not end up essentially with a bundle of medicine strips but lifestyle change and such other advices makes predictive genetic test still more different. But its power to curtail mortality and morbidity through targeted screening, surveillance and prevention is overwhelming and cannot be denied.
Predictive genetic testing for lifestyle diseases such diabetes type II, osteoporosis and atherosclerosis will continue to attract attention as and when more information is made available on the awareness front. geneOmbio Technologies Private Ltd at its Pune-based central genomics laboratory continues to make available such novel genome analysis products and keep working relentlessly in making the society aware about the significance of these category of tests.
-Sachin S. Purohit is MD &. Pratap N. Mukhopadhyaya is CEO & Head, R&D
Operations of geneOmbio technologies, Pune