The current special issue of the Apollo Medicine celebrates the progress made by genetics, particularly human genetics in modern medicine and health care. Among several key discoveries and innovations, the deciphering of the double helix structure of the deoxyribonucleic acid (DNA) by James Watson and Francis Crick in 1953 unquestionably remains the most significant milestone. This special issue is dedicated to this landmark discovery that conceptually revolutionized the cell and molecular biology with far-reaching implications. It offered the much-needed physical evidence for heredity and its correlation with physical and many other traits. We are now cherished with its applications and positive impact in managing the human disease and prospects of optimal human health.
The concept of heredity in living creatures dates back to the ancient times. Interpretations of hymns and inscriptions in the Vedas, particularly the Rigveda, refer to heredity. Scientists and the Vedic scholars have revisited the evidence collected from the Indus Valley Civilization consistent with the genetic evolution and recombination. It is claimed that some of the hymns when decoded relate to the complex processes such as the synthesis of chromosome, DNA replication, protein translation, and nucleotide pairing for nuclear reaction (https://www.dnaindia.com/bangalore/report -rig-veda-a-treasure-trove-of-transgenics-1506241). The team in the Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology is actively pursuing the role of the ancient Vedas in the context of modern genomic technologies (https://www.igib.res.in/?q = ayurgenomics/).
There are many anecdotes from the ancient Greek literature and mythology that relate to human heredity and health implications. Most of these are related to the times of Hippocrates around 380–350 BC. There is reference to “mothers who bear sons dying of bleeding when wounded in the war.” Many acknowledge this as a clear reference to the classic X-linked hemophilia A. Perhaps the most pertinent evidence comes from the Aristotle’s “Generation of Animals” book, in which the heritable factors are argued with the laws of inheritance, mainly during the act of reproduction (Devin Henry, 2006. Aristotle on the mechanism of inheritance. Journal of the history of biology; doi 10.1007/s10739-005-3058-y.).
There is an ongoing argument whether Aristotle’s Greek philosophy favored natural selection theory for the biological evolution, later put forward by Charles Darwin? Despite the differing views on Charles Darwin’s theory of evolution governed by the natural selection, many agreed with the concept of hereditary factors put forward in the Darwin’s famous book “On the origin of species.” Several years later, the evidence for dominant and recessive hereditary factors was provided by Gregor Mendel in his elegantly illustrated mathematical experiments on garden pea plants with different physical traits. However, this work was not appreciated for almost 60 years; when in the early 1900s, biologists became serious about the Mendel’s laws of inheritance and the science of heredity. This generated tremendous interest on the mysteries of heredity material, possibly located in the nucleus of the cell.
During the early part of the 20th century, a large amount of data was generated on physical traits like height, and functional traits like intelligence, in the context of positive or negative heredity. The term “eugenics” was coined by Francis Galton, the great grandson of Charles Darwin. Whist this movement was full of good intentions, sections of the society started using this as the divisive and discriminatory tool both in the USA and UK, including the parts of the Europe. Later, the eugenic ideas and logic became the central theme of the Nazi Germany as evident from the doctrine of the Race Hygiene clearly targeted at Jews, Gypsies, and a few other minority sections, including people with physical and learning disabilities.
Despite the negative impact of the World War II and the eugenics movement, the progress in genetics and heredity continued. The period between 1950 and 1960, described as the golden decade of genetics, is decorated with discoveries and innovations in genetics, notably the Watson-Crick’s double helix model of the DNA, Tjio-Levan’s 46 chromosomes in the human cell, and Hargobind Khorana’s triple nucleotide genetic code governing the assembly of amino acids for the peptide molecule synthesis. Since then the progress in genetics, later expanded to genomics, led to many more discoveries to the successful completion of the Human Genome Project in early parts of the new millennium. In 2003, advances in molecular technology allowed nearly 98% sequence of the human genome. The remainder 2% of the genome, comprising the repetitive DNA in telomeres (the terminal ends of the chromosomes) was eventually sequenced in 2022.
Although the practice of genetics in medicine became established in the early 1970s, it remained miniscule restricted to a few chromosomal disorders, selected multiple malformation rare dysmorphic syndromes, and common monogenic (single-gene Mendelian) diseases. The concept of polygenic multifactorial diseases was appreciated with the mathematical models of heritability and linkage disequilibrium. The practice of genetic counseling found its firm base with the development of genetics in medicine. This period witnessed rapid advances in the genetic laboratory diagnosis from the early days of cytogenetics to molecular cytogenetics, notably the fluorescence in situ hybridization. The introduction of techniques of molecular DNA analysis allowed the focus on DNA fragments using the restriction enzymes and the recombinant DNA methods.
Several different types of DNA laboratory techniques were developed and applied in clinically useful family linkage studies, gene mapping by positional cloning, genetic risk analysis, prenatal diagnosis, and predictive genetic testing. The DNA analysis received the much-needed impetus with the discovery of the polymerase chain reaction. The modern genetic or genomic laboratory is equipped with the sophisticated facilities for the state-of-the-art genomic diagnosis to as low as at around 100 base pairs. The next-generation sequencing is now available targeted at single gene, multiple gene panel, small and large reads, RNA sequencing, the mitochondrial genome, and epigenome. The microarray chromosome analysis (array comparative genomic hybridization), targeted clinical exome sequencing, whole-exome sequencing, and whole genome sequencing are now available at progressively lower costs. However, new challenges are emerging with huge genome sequencing data, variants of unknown significance, interpretation of the population specific genome sequences, and the relevance of evolutionary conserved genome polymorphisms. New related disciplines are emerging, specifically clinical bioinformatics, computational systems, functional genomics, and many more.
Every clinician, practicing any system of medicine, aims for precision and personalized care to all patients, and if necessary, for the family. Although the clinical evaluation remains the most essential part of medicine, the outcome is closely related to the efficacy and accuracy of diagnostic methods used, whether biochemical, immunological, histopathological, or radio imaging. Most of these lack the much-needed high-order sensitivity and specificity. This gap is now narrowed down to extremely small level with the rapid incorporation of next-generation and emerging future genome technologies. The clinician can now confidently offer precision and personalized care with the added options of predictive and preventive, the 4Ps of modern medicine, now expanded to include preemptive and participatory elements (6Ps Medicine). Several new therapeutic and prophylactic modalities are now possible managing different common and rare diseases. Genomics remain central to the new modern medicine with the acceptance of genomic health care as the preferred choice. However, inclusion of other life sciences is important denoted with OMICS, such as transcriptomics, proteomics, metabolomics, phenomics, microbiomics, glycomics, and lipidomics. There is a strong drive for the modern genomics-led multi-OMICS medicine with the focus on multidisciplinary integrated health care.
The future of genomics led critical, and the specialist care is undoubtedly bright with the prospects of precision and personalized health care. This is continually improved with the development and availability of novel highly sensitive diagnosis options and new drugs and vaccines. Clearly, this would need to modify and modernize the medical and health-care education and training for developing highly skilled and competent workforce. There would be a constant need for adequately funded basic and clinically applied translational research and development (R and D) infrastructure and carefully regulated outcomes. Clinicians, genomic medicine practitioners, and related health-care providers would need to give due care and attention to the ethical, legal, and social issues embedded in the core of the genomic health care.
Finally, this special issue would not have been possible without the contributions of many colleagues and supporters, who worked as the team to write, develop, and deliver in a very short time frame. Many other colleagues worked extremely hard to ensure quality and elegantly produced the special issue of the Apollo Medicine. The Apollo Genomics Institutes across India dedicate this issue to many of our patients and families for the courage and perseverance fighting and/or living with common and rare genetic diseases. They need to be reassured about the bright future led by new advances in genomics and multi-OMICs.
Author wholly contributed to this Editorial.