Tuesday, February 11, 2014
With the full sequencing of the human genome in 2003 and the drastic fall of DNA sequencing costs in the last decade, there were great expectations in the scientific community as well as in the public’s mind that the heath care sector would see dramatic changes. The era of personalized medicine seemed to have arrived heralding individualized treatment regimes based on a person’s genome. However neither has this expectation been met nor has the practice of medicine changed significantly, yet.
The main reason for the seeming lack of progress has been the amazing complexity that the genomic data presented. Every step forward seemed to open up more avenues than scientists could explore and it soon became clear that it would take decades of effort to understand what it took Nature millions of years to evolve. The first revelation was rather surprising – contrary to the initial expectation that the human genome would contain about 80 to 100,000 genes, there were only about 20,000 genes to do the job. Not only that, many plant genomes were bigger and more complex than the human genome and hence bigger did not mean better! More surprising revelations were on the way - decoding the gene sequences were shedding very little light on diseases or even traits. Even characteristics that looked genetically straightforward like ‘height’ could not be pinned down on specific genes. The non coding regions of the genome - what was considered once as ‘junk DNA’ – was playing an important part in regulating gene activity. Other factors such as environment, food and even stress level were playing a major role. Further, the importance of epigenetics (heritable, chemical modifications to the genome that would affect the function without changing the sequence) and the microbiome (the microbial cells in the human body that not only number about 10 times more than the human cells, but also play a significant role in digestion and immunity) was sufficient proof that the belief that the genomic data was the entire and only blueprint for the development of the organism was naïve at best.
At the same time, what we could understand of the genome offered tantalizing glimpses into our past, present and future health. The genomic data proved beyond doubt the origin of humans in Africa and we could now trace our migratory path over the rest of the earth in the last 60,000 years. During this migratory journey our species did breed to a minor extent with other homo species like Neanderthals and Denisovans (and maybe others as well), acquiring 5 to 8% of their genes. As we split into different ethnicities in different regions, the climate, food and other environmental pressures led to different groups acquiring different genetics mutations leading to changes in appearance as well as different capabilities like lactose tolerance, disease immunity and so on. We could now understand why many drugs create adverse reactions in some and why we react so differently to various disease causing pathogens. Genes causing over 6000 rare inherited diseases have now been identified. We have been able to pinpoint specific genetic mutations that lead to cancer in about 35 to 40 % of the cases. A number of drugs that can treat these cancers have been released and many more are on their way. Genes that play a major role in cardiovascular diseases, diabetes etc. have been identified and we are on the path to reaching the dream of predictive and personalized medicine.
While there is no doubt that we are moving in the right direction, we still need a considerable amount of genomic studies across the world. Surprisingly, it has been a recent realization that India is a treasure trove for genomics. Over the last 2000 years, unknowingly, India has been the home to the largest genomic experiment in human history. Due to religion, caste and geography, the Indian population has been split to over 4500 groups and till recently has been strictly breeding within the groups. This has created unique genetic mutations that when co-related with susceptibility to diseases can lead to major discoveries. India also suffers from a higher burden of inherited diseases due to inbreeding and consanguinity and thus a better understanding of the genome can lead to proper treatment and cure. Counseling and carrier testing of couples can significantly reduce the occurrence of many inherited diseases thus reducing the burden on the family as well as the society.
India is also home to traditional systems of medicine like Ayurveda which promoted ‘personalized’ medicine 3000 years ago. However, the science was very basic at that time and hence there was no clear understanding of why the herbal medicines or treatment practices worked. Now, if we can combine the genomic understanding with traditional practices and conduct extensive studies across our population, we would be able to make a difference in the healthcare sector by providing solutions in a cost effective manner.