Future of Medicine: Answer lies in Human Genome

https://meditropics.com/future-of-medicine-answer-lies-in-human-genome/

*Pangtey GS,

*Director Professor, Department Of Medicine, LHMC, New Delhi.

 

In past 4-5 decades there has been breath-taking progress in the field of medical technology regarding molecular genetics and genomic medicine. An organism’s complete set of DNA structure is called genome and genomics is the study of full genetic makeup/ blue print of DNA of one organism and their interaction with other genes and environment. In today’s scenario, the maximum advances in genomics has been observed in diagnosis and treatment of oncology and paediatric specialities, although in near future this is envisaged to expand to many more subspecialties of medicine.

The blueprint encoded into the strands of human DNA carry the secrets to our individuality, our disease susceptibility and our responsiveness to treatment. This genetic information about individual’s unique response versus adverse reaction to any given medication will be the foundation stone of future precision medicine and personalized care. The one-size-fits-all approach will be very soon modified to precision prescribing, which will revolutionize therapeutics, ushering in a new era of truly personalized medicine.

The arrival of genomic medicine heralds paradigm shift in healthcare, transforming our understanding of disease aetiology, prognosis, and therapeutic intervention. Each genome sequence is revealing intricate tangles of genetics variations that shapes human health and disease. Every day we are discovering rare monogenic Mendelian disorders as well as complicated multifactorial diseases with genome sequence analysis.

In 1987, the Human genome project (HGP) was launched as the biggest, costliest and most important biomedical research project. The human genome consists of approximately 3 billion DNA base pairs or 20,000 to 25000 genes. The above genomic information is located inside 23 chromosomes present in the nucleus of each human cell. The HGP was completed in 2003 and took more than a decade for deducing the complete set of genetic sequencing of human. Since then, in last two decades the genomic technology has advanced so rapidly that the whole human DNA sequencing speed has increased from 1000 base pairs per day to 1000 base pair per second.1 This has also reduced the cost of whole genome sequencing in past two decades, from $3 billion to $600 only, and given the opportunity to researchers to analyze the whole data for various undiscovered and rare diseases with the help of large language model (LLM) of super computers artificial intelligence. In this issue of journal Bansal et al., reviewed the various technique of Newer generation sequencing (NGS) 2and how it is helping in diagnosis and treatment of various genetic diseases as well as treatment of some rare genetic diseases with single gene mutation (e.g.hemophillia etc. ).

In year 1920 FDA approved first Ex-vivo cell-based gene therapy (Casgevy) in Sickle cell disease patients who are >12 years of age and have recurrent non-occlusive disease. It is based of CRISPR/ Cas9 based gene editing technology in which patients hematopoietic stem cells were taken and mutated DNA is cut, edited/ repaired and modified stem cells were transfused back in patients. The engrafted cells increases HbF production in bone marrow leading to reduction in sickling crisis.3 In another example of use of NGS sequencing in diagnosis of undiagnosed multisystem neurologic disorder of infant’s published by Wright et al., they conducted large scale sequencing study involving more than 13,500 families with probands having severe, probably monogenic, difficult-to-diagnose developmental disorders in UK and Ireland. They reported on an average one candidate variant per parent-offspring trio and diagnosed 41% of probands (5502 of 13,499) suggesting the usefulness of genomic study in undiagnosed multisystem genetic diseases in paediatric age group.4

Genomics study can have vast implications in public health and disease prevention, especially in diseases which can be screened early and have curative or preventive treatment. CDC Tier 1 disease recommendation include population based genomic testing for hereditary breast and ovarian cancer syndrome, Lynch syndrome (colon cancer), and familial hypercholesterolemia.5 By identifying individuals at heightened risk of disease, genomics empowers proactive healthcare initiatives, shifting the focus from reactive treatment to proactive prevention.

All these studies suggest that there will be huge potential for human genomics and their utilization in routine clinical practice. All this will greatly benefit the humankind. But, the realization of genomics’ transformative potential also depends on ethical, legal, and societal considerations. Questions surrounding privacy, consent, and equitable access loom large in the genomic landscape, underscoring the need for robust governance frameworks and inclusive policies. Other potential roadblocks will be analysis of very high volume of genomic data which will require LLM of AI, cost-effectiveness of population based screening and lack of insurance cover, difference in regional genetic variation and effects of environmental factors in expression of genomics. There will be humongous learning curve for physicians to understand the difference between genetic variations of significance versus non significance.

As we chart our course towards the future of medicine, let us embrace the boundless possibilities of genomics with humility, curiosity, and empathy. Let us harness the power of our genetic heritage to unravel the mysteries of human health and disease, marching towards the path of healthier, more resilient universe. Let the genomics be our guiding star and illuminates us towards the future of medicine where every individuals receives personalized medicine tailored to their unique genetic blueprint.

References:

  1. Collins FS, Doudna JA, Lander ES, Rotimi CN. Human Molecular Genetics and Genomics – Important Advances and Exciting Possibilities. N Engl J Med. 2021 Jan 7;384(1):1-4. doi: 10.1056/NEJMp2030694.
  2. D Bansal. Next generation Sequencing: Review. Med Clin Tropics 2024(1):1-10
  3. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease | FDA
  4. Wright CF, Campbell P, Eberhardt RY, Aitken S, Perrett D, Brent S, et al. Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland. N Engl J Med. 2023 Apr 27;388(17):1559-1571. doi: 10.1056/NEJMoa2209046. 
  5. Guzauskas GF, Garbett S, Zhou Z, Schildcrout JS, Graves JA, Williams MS et al. Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis. Ann Intern Med. 2023 May;176(5):585-595. doi: 10.7326/M22-0846.Bottom of Form