Genomics For Health, Food And Conservation

Do you ever wonder why Hollywood star Angelina Jolie decided to remove her breasts despite no disease, how COVID-19 variants were determined so quickly during the pandemic, or why and how scientists developed golden rice? While this article focuses on how genomics has addressed various biological problems such as healthcare, agriculture, and biodiversity, emphasizing Nepal's progress, challenges, opportunities, and recommendations, it will explore answers to these intriguing questions. Genomics is a branch of biology that studies the complete deoxyribonucleic acid (DNA) and all genes within an organism. The understanding of genomics in ancient times was based on observations about heredity and characteristics. While ancient civilisations lacked scientific tools to study DNA and genes, their practices and assumptions often suggested the basic principles of heredity. For example, in Hindu society, there is a practice that people from the same lineage (in Sanskrit: Gotra) are forbidden to get married to prevent inbreeding, which can increase the risk of recessive genetic disorders and other health issues in offspring. The basis for modern genomics is Mendel's Laws of Inheritance, published in 1866 and progressed further by the discovery of the DNA structure in 1953 by Watson and Crick.

Key milestones 

The revolution in genomics started at the beginning of this century, starting with the completion of the Human Genome Project (THGP) in 2003. This project was completed in 13 years with the collaboration of scientists from six countries (China, France, Germany, Japan, the UK, and the USA) at approximately $3 billion. It produced the first-ever complete human genome sequence, which served as a foundation for research in many aspects of human biology.

THGP used the traditional DNA sequencing method, the Sanger sequencing method, to sequence the human genome. In 2005, Roche unveiled the first-ever commercially available advanced sequencing platform, next-generation sequencing (NGS). Since then, several companies have developed NGS platforms, such as Illumina, Ion Torrent, Complete Genomics, Pacific Bioscience, and Oxford Nanopore. The rapid advancement of NGS helped to reduce genome sequencing costs and time. The same human genome THGP sequenced can be sequenced in two days at only $1000.

NGS has been widely used not only for diagnosis but also for the prediction and treatment of genetic diseases such as cancer. For example, if the altered BRCA1 and BRCA2 genes are present in women, there is a high risk of developing breast and ovarian cancer. In 2013, Hollywood star Angelina Jolie revealed that genomic testing had identified a mutation in her BRCA1 gene. As a precautionary measure, she chose to undergo a mastectomy to reduce her cancer risk significantly. NGS has reshaped the management of infectious diseases by facilitating the rapid identification, characterization, and monitoring of pathogens. The use of NGS to sequence the SARS-CoV-2 genome during the COVID-19 pandemic has proven its importance by helping scientists to identify variants like Delta and Omicron swiftly. Similarly, genomic data was also used to predict drug-resistant strains. In addition to healthcare, NGS has applications in agriculture and biodiversity conservation. For instance, genomic data showed that its population has low genetic diversity; thus, conservationists developed a strategy to avoid inbreeding.

CRISPR-Cas9 can precisely edit genes; thus, it has several advantages, such as modifying genes for treating genetic diseases and improving crops and livestock. Although this technique was recently developed, there are already several CRISPR-based gene therapies available to treat various diseases such as HIV infection, Duchenne muscular dystrophy, and sickle cell disease. In agriculture, using this technique, scientists developed genetically modified 'golden rice' with higher vitamin A content to fight vitamin A deficiency in developing countries. Similarly, using CRISPR, scientists developed hornless cattle and chickens resistant to certain viral diseases.

Single-cell genomics involves studying genomic materials such as an individual cell's DNA, RNA, and protein. Using genomic information among individual cells within a tumor can identify cancer-related mutations and guide targeted treatment.

Since NGS generates a vast amount of genomic data, the combination of bioinformatics and artificial intelligence (AI), especially machine learning algorithms, is helping scientists to analyze and interpret genomic data with high speed and accuracy. Therefore, AI algorithms accelerate drug discovery, optimise agricultural genomics, and monitor biodiversity.

Genomics in Nepal

Genomic research in Nepal is in a very early stage. Although there were few initial attempts for limited genomics by some academic institutions, government labs, and the private sector, momentum was only realised after the COVID-19 pandemic. Establishing an NGS lab at the National Public Health Laboratory (NPHL) with the help of the World Health Organisation (WHO) enabled the sequencing of SARS-CoV-2 variants. Non-profit organizations like the Centre for Molecular Dynamics Nepal (CMDN) and private companies like the Kathmandu Centre for Genomics and Research Laboratory (KCGRL) are trying to integrate genomics into healthcare and environmental management.

In agriculture, a limited genetic study of crops like rice, wheat, buckwheat, lentils, and finger millet has identified traits for climate adaptation and disease resistance. Efforts like the Nepal Tiger Genome Project highlight the country's steps in biodiversity conservation. However, most genomic research in Nepal relies on international collaborations due to limited infrastructure and skilled personnel. For example, the author of this article, together with the team members from Austria, Germany, and Thailand, has characterised the genetic diversity of forest trees such as sal, sissoo, and neem in Nepal, respectively.

Integrating genomic technology in Nepal faces significant hurdles. Because genomics requires an advanced laboratory and bioinformatics infrastructure, a substantial investment is needed, which is absent at present in Nepal. The country's brain drain problem worsens due to the lack of a skilled workforce in genomics. Furthermore, outdated policies like the Biotechnology Policy 2006 and the National Science, Technology, and Innovation Policy 2019 lack explicit regulatory provisions to oversee genomic research and data privacy. Public awareness of genomics and its applications is negligible and hinders its integration.

Despite the limitations and challenges, genomics in Nepal holds immense potential, specifically in healthcare, agriculture, and biodiversity conservation. Its importance in managing infectious diseases has already been proven by the ability to sequence and monitor emerging pathogens like SARS-CoV-2 and other pathogens by NPHL. In personalised medicine, genomics can facilitate the early detection and treatment of hereditary diseases such as cancer and genetic disorders. Furthermore, the characterization of the genetic makeup of Nepal's ethnically diverse populations reveals distinctive susceptibilities and adaptations that will help to formulate an effective public health strategy.

In agriculture, genomics has vast potential to modernize Nepal's agriculture to improve agricultural productivity and food quality and ultimately ensure food security. Similarly, genome sequencing of essential crops can facilitate the detection of vital genetic traits of crops and livestock, such as high yield, drought tolerance, and disease and pest resistance. Furthermore, genetic fingerprinting of native crops and medicinal plants can also be presented as evidence to claim intellectual property rights in case of any dispute with other countries.

Nepal is rich in biodiversity; thus, genomics has promising prospects in biodiversity conservation. Sequencing genomes of threatened species like the Bengal tiger, musk deer, red panda, rhinos, and snow leopard can provide insight into the genetic diversity of fragmented populations and help design inbreeding risk-free conservation strategies for those species. Similarly, genomic analysis of native plant species can facilitate the conservation of rare and endemic flora while understanding genetic responses to changing climatic conditions.

In conclusion, advancement in genomic technology is happening rapidly, and developed countries have already adopted this technology to solve diverse biological problems. Although Nepal has made some progress in genomic research, the government is still lagging far behind in harnessing the benefits of this technology due to a lack of clear strategy and resources. With international partnership and strategic investment, Nepal has immense potential to benefit from this technology for its scientific advancement and sustainable development.

(Dr. Pandey is a senior scientist at Molecular Research LP (a genomic core lab) in Shallowater, Texas, USA.)