Biotechnology & Health Technology: Tools, Therapies, Vaccines and Biosafety

Gene therapy is classified on two axes. Somatic therapy changes body cells, so the change ends with the patient; germline therapy changes eggs, sperm or embryos, so the change is inherited by every descendant — which is why it is the ethical red line almost everywhere, and why India’s national guidelines confine gene therapy to somatic cells. Ex vivo therapy takes cells out, modifies them in the laboratory and returns them; in vivo therapy delivers the gene directly into the body, usually inside a viral vector.

CAR-T cell therapy is the best-known ex vivo example. A patient’s own T cells are collected, given a gene for a chimeric antigen receptor that recognises a marker on cancer cells (most often CD19 on cancerous B cells), multiplied and infused back, where they hunt the cancer. It is used for certain leukaemias and lymphomas. India’s first indigenous CAR-T therapy, NexCAR19, developed by ImmunoACT (incubated at IIT Bombay) with the Tata Memorial Centre, was approved by the drug regulator CDSCO in 2023, at a fraction of the cost of the imported therapies.

CRISPR-Cas9 cuts both strands of DNA at the site its guide RNA matches (next to a short motif called the PAM). What happens next depends on the cell’s own repair. The quick, error-prone non-homologous end joining usually inserts or deletes a few letters and knocks the gene out; homology-directed repair copies a supplied template and so can write in a precise change. Newer base editors and prime editors change single letters without a double-strand break, which lowers the risk of unwanted damage. The first CRISPR medicine, Casgevy (exa-cel), approved in the United Kingdom in November 2023 and the United States in December 2023, edits a patient’s blood stem cells ex vivo so they switch fetal haemoglobin back on — a treatment for sickle cell disease and beta-thalassaemia, both heavy burdens in India’s tribal and other communities. India’s National Sickle Cell Anaemia Elimination Mission was launched in 2023.

In March 2022 the Environment Ministry exempted SDN-1 and SDN-2 genome-edited plants that are free of foreign DNA from the biosafety rules that apply to genetically engineered organisms, and the Department of Biotechnology issued guidelines for their safety assessment the same year. The logic is that such a plant carries a change that could in principle have arisen by mutation or conventional breeding. In May 2025 the Indian Council of Agricultural Research released India’s first two genome-edited rice varieties, edited without inserting foreign DNA. SDN-3 products remain under the full GM regime described later in this chapter.

The ethical objection to embryonic stem cells — an embryo is destroyed to obtain them — was answered in 2006, when Shinya Yamanaka showed that adult mouse cells could be reprogrammed into a pluripotent state by switching on just four genes (Oct4, Sox2, Klf4 and c-Myc); human iPSCs followed in 2007. Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine with John Gurdon, who had shown in 1962 that the nucleus of a specialised frog cell could still direct the development of a whole frog. iPSCs made from a patient’s own skin avoid immune rejection and let researchers grow "disease in a dish", though their tendency to form tumours has kept most uses experimental.

The one stem-cell treatment with decades of evidence is the haematopoietic stem-cell transplant for blood cancers, thalassaemia and some immune disorders. Beyond such approved uses, Indian regulators have repeatedly warned against clinics marketing stem-cell "cures"; stem-cell and gene-therapy products are treated as new drugs under the New Drugs and Clinical Trials Rules, 2019, so they need trials and approval like any other medicine.

Reproductive cloning aims at a new individual genetically identical to the donor; therapeutic cloning uses the same nuclear transfer only to obtain an embryo from which matched stem cells can be taken, with no intention of a pregnancy. A clone is not a perfect copy: its mitochondrial DNA comes from the egg donor, not the nucleus donor, and its traits are also shaped by the uterus, by epigenetic marks and by environment. Indian institutions have cloned livestock for conservation and breeding — after NDRI’s buffalo, Noori, a Pashmina goat cloned at SKUAST-Kashmir in 2012, is the example most often cited.

India regulates genetically engineered organisms under the Environment (Protection) Act, 1986, through the Rules for the Manufacture, Use, Import, Export and Storage of Hazardous Micro-organisms, Genetically Engineered Organisms or Cells, 1989 — usually called the 1989 Rules. The Environment Ministry is the nodal ministry, which is why the apex committee sits there rather than in agriculture. The rules name six competent authorities:

GEAC clearance is not the end of the road. Seeds also need registration under seed law, and GM food — imported or domestic — needs the approval of the Food Safety and Standards Authority of India under Section 22 of the Food Safety and Standards Act, 2006. Internationally, India is a party to the Cartagena Protocol on Biosafety (adopted 2000, in force 2003), which governs the cross-border movement of living modified organisms under the Convention on Biological Diversity.

• Bt cotton, two generations. Bollgard I (2002) carried one gene, cry1Ac; Bollgard II (2006) stacked cry1Ac and cry2Ab to delay resistance. By the mid-2010s pink bollworm had nonetheless evolved resistance in several cotton regions, beginning in Gujarat — the textbook case for refuges of non-Bt plants and for not relying on one toxin.
• Herbicide-tolerant Bt (HTBt) cotton, which also survives glyphosate, is not approved in India; its spread through illegal seed is an enforcement problem, not a sanctioned technology.
• GM mustard DMH-11, developed at Delhi University’s Centre for Genetic Manipulation of Crop Plants, uses the barnase–barstar system (a male-sterility gene and its restorer) to make hybrid seed easy to produce, with a bar gene for herbicide tolerance as a marker. GEAC recommended its environmental release in October 2022; the decision was challenged before the Supreme Court, and commercial cultivation has not followed.
• Neighbouring Bangladesh has grown Bt brinjal commercially since 2014 — a useful contrast with India’s 2010 moratorium.

Every vaccine shows the immune system an antigen — a recognisable piece of the pathogen — without causing the disease, so that memory B and T cells are ready when the real pathogen arrives. That is active immunity: it takes a week or more to develop and lasts. Platforms differ only in how the antigen is delivered, and that choice decides how strong the response is, how many doses are needed and how cold the vaccine must be kept.

• Malaria vaccines: WHO recommended RTS,S in 2021 and R21/Matrix-M — developed at Oxford and manufactured by the Serum Institute of India — in October 2023; both target the P. falciparum sporozoite.
• Polio: India’s last wild case was in January 2011, and the WHO South-East Asia Region was certified polio-free in March 2014. Because the live oral vaccine can, very rarely, mutate back and circulate as vaccine-derived poliovirus, the world switched from trivalent to bivalent oral vaccine in April 2016 and added injectable IPV.
• Delivery: the Universal Immunisation Programme dates from 1985; Mission Indradhanush (December 2014) targets children and pregnant women left out of routine immunisation; eVIN (2015) tracks vaccine stocks and cold-chain temperatures digitally.

A monoclonal antibody is one antibody, against one target, made in bulk. The method, the hybridoma, was devised by Georges Köhler and César Milstein in 1975 (Nobel Prize, 1984): an antibody-producing B cell, which dies in culture, is fused with an immortal myeloma (cancer) cell, and the hybrid both lives indefinitely and secretes the single antibody. Monoclonals now treat cancers (trastuzumab against HER2-positive breast cancer, rituximab against B-cell cancers), autoimmune disease and some infections, and they are the working part of a home pregnancy test, which detects the hormone hCG. Under the older naming scheme the suffix told the origin: -ximab chimeric, -zumab humanised, -umab fully human.

Alexander Fleming noticed in 1928 that the mould Penicillium notatum killed bacteria around it; Howard Florey and Ernst Chain turned penicillin into a usable drug, and the three shared the 1945 Nobel Prize. Streptomycin (1943), isolated from the soil bacterium Streptomyces in Selman Waksman’s laboratory, was the first antibiotic effective against tuberculosis. Antibiotics work by hitting structures that bacteria have and human cells lack or build differently:

Viruses have no cell wall and no ribosomes of their own — they use the host’s — so antibiotics do nothing against a viral infection; antivirals instead block viral enzymes, as oseltamivir blocks influenza’s neuraminidase or reverse-transcriptase inhibitors block HIV. Antimicrobial resistance (AMR) is natural selection at work: a few bacteria survive a drug by destroying it (beta-lactamases; the carbapenem-destroying NDM-1, first described in 2009 in a patient treated in New Delhi), pumping it out (efflux pumps), changing the target or keeping it out. Resistance genes then spread sideways between bacteria on plasmids — horizontal gene transfer — which is why resistance can jump between species. Overuse in people, use as growth promoters in livestock, over-the-counter sales, unfinished courses and antibiotic-laden factory effluent all speed it up.

The WHO AWaRe classification (2017) sorts antibiotics into Access (first choice for common infections), Watch (higher resistance risk, to be monitored) and Reserve (last resort, such as colistin). Tuberculosis shows what resistance costs: multidrug-resistant TB resists at least the two most powerful first-line drugs, isoniazid and rifampicin. India’s programme was renamed the National Tuberculosis Elimination Programme in 2020, and India set itself the goal of ending TB by 2025, five years ahead of the global 2030 target.

More than 99.9% of the DNA sequence is the same in any two people. DNA fingerprinting, devised by Alec Jeffreys at Leicester in 1984, looks at the small part that is not: stretches of non-coding repetitive DNA in which a short unit is repeated a variable number of times — VNTRs (minisatellites) and the shorter STRs (microsatellites). The number of repeats at many such sites together is unique to a person. The classic method cut DNA with restriction enzymes, separated the fragments on a gel, transferred them to a membrane (Southern blotting) and revealed them with labelled probes; modern forensic labs amplify a standard panel of STRs by PCR, which works on traces as small as a hair root.

• Identical (monozygotic) twins share the same DNA profile — the one case fingerprinting cannot separate.
• Mitochondrial DNA passes only from the mother, and the Y chromosome only from father to son, so each traces one line of descent — useful for identifying remains and for population history.
• In India the technique was developed by Lalji Singh at the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, using probes derived from repetitive DNA of the banded krait; the Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, now does this work under the Department of Biotechnology. A bill to regulate forensic DNA databanks was introduced in 2019 but did not become law.

Reading a whole genome has gone through three generations: Sanger sequencing (1977), which reads one fragment at a time and finished the Human Genome Project; next-generation sequencing, which reads millions of short fragments in parallel and made a human genome affordable; and long-read sequencing (nanopore and similar), which reads long stretches in one go and can be done on a portable device in the field. India’s own projects:

The policy frame for all of this is the BioE3 policy (Biotechnology for Economy, Environment and Employment), approved in August 2024, which backs biomanufacturing in areas such as bio-based chemicals, smart proteins, precision biotherapeutics and climate-resilient agriculture. Its industry-facing arm is BIRAC (2012), the Biotechnology Industry Research Assistance Council set up by the Department of Biotechnology.