In January 2015 President Barack Obama announced the Precision Medicine Initiative to not only bring us closer to curing diseases like cancer or diabetes but also closer to the dream of personalized medicine. Advancements in the fields of high-throughput genomics and proteomics have made it possible to design prevention and treatment strategies based on individual variability.
It has been a long way to reach this point in time when precision medicine is a reality. But the concepts of precision medicine date back to the era of Greek philosopher and mathematician Pythagoras when in 510 BC he observed that ingestion of fava beans were fatal to some individuals and not to others. Today we know this phenomenon as Favism or glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency). Genetic mutations in G6PD gene predispose individuals to potentially fatal hemolytic anemia in the presence of certain foods, drugs, or chemicals. Pythagoras at that time did not have the tools or resources or technology to come up with any hypotheses explaining the differential reaction to fava beans consumption. For years, genetic material was thought to be contained in the cellular proteins. Oswald Avery, a Canadian-born American physician and medical researcher, in 1944 showed for the first time that DNA was the carrier of genes in cells and not proteins. This paved the way for deciphering the DNA crystal structure by James Watson and Francis Crick in 1953. This was the birth of modern genetics and molecular biology. Fifty years later, in 2003 the complete reference human genome sequence was made available to the scientific community.
The Human Genome Project was a 13-year international project with the sole objective of determining the DNA sequence of the entire euchromatic human genome. It took 13 years and $3-billion to publish the first reference human genome sequence. Thanks to the advances in sequencing and computational technologies we can now sequence the entire human genome in a matter of hours for less than $1000. Very recently we saw completion of the 1000 Genomes Project - an effort to establish by far the most detailed catalog of human genetic variation. The last decade has seen unprecedented advancement in high-throughput genomics. This, coupled with rapidly declining sequencing costs has enabled scientists to perform large-scale genetic screens to understand the molecular mechanisms underlying human diseases. A lot more needs to be done.
Hundreds of thousands of human genomes representing different populations have already been sequenced and hundreds are being sequenced every day. The prospect of applying precision medicine concepts at population scale has come closer to reality only due to the advancements in genomics, molecular biology, bioinformatics and other “omics” methods like transcriptomics, proteomics, metabolomics. Genome sequencing is being more commonly used in the clinics and patients are getting benefited by the personalized treatment recommendations. This growing application of clinical sequencing and the knowledge gained from first generation of clinical sequencing projects has generated intriguing insights into the utility of this technology in the clinical setting. Precision medicine is all about understanding the molecular mechanisms underlying a trait or disease and then applying the concepts to individual care. Molecular signatures underlying these traits or diseases vary by populations, sub-populations and individuals themselves.
We are living in very exciting times of progress and collaboration. The reality of sequencing complete human genomes at scale has renewed our hope in understanding the genetic etiologies underlying complex diseases like diabetes or cancer. What was just a dream a generation ago is now a reality. Not for South Asia though. We know very little about the genetic diversity of South Asian populations / sub-populations to design or recommend personalized therapies.
In the next part I will try to elaborate on what is so special about the South Asian population and why it is important to understand the genetic diversity of this region.