Science and Technology

• The term ‘Genetic Engineering’ was coined in 1951 by Jack Williamson. 
• It is the process of direct human manipulation of the organism’s genome.  
• It involves introducing the foreign DNA into the organism of interest to add one or more traits that aren’t found naturally in the organism. 
• The organism thus produced is known as GMO or Transgenic organism.

• Genome is relatively resistant to change. To deter any changes from being inadvertently made to DNA, cells have inherent mechanisms to proofread and repair their genetic code. Remarkably, researchers have taken advantage of the cell’s DNA repair mechanisms to achieve genome editing. 
• To accomplish this, scientists can use
  • Artificially engineered enzymes called Nucleases act as molecular scissors and are used to crack open DNA strands.  
  • Once the break is introduced in DNA, the cell will detect the problem & quickly activate repair machinery. 
  • DNA sequence designed to be inserted is also sent along with a Nuclease, such that when a cut is made in the DNA, the cell’s own repair mechanism can use the DNA sequence supplied to replace an existing DNA sequence. 
• This method allows scientists to change the genetic makeup of cells directly.  

Genetic material can be inserted from the same species as well as other species. Accordingly, they are known as Transgenic and Cisgenic GMOs.

1. Gene Delivery Tools

• Genes are inserted into the body using vectors which are usually viruses.
• Viruses can produce other problems like
  • Toxicity
  • Immune response
  • Inflammatory response
  • Gene control and  targeting issues

2. High Costs / Equity Concerns

• The whole process is quite expensive and hence not inclusive. It will create the division in society between haves and have-nots.

3. Ethical Dilemma

• Principal concerns include morality, eugenics helping the fittest to survive, ongoing clinical debates about informed consent, religious debate, the possible rise of clones, designer babies, and possibly super-humans.

4. Informed Consent

• In the case of germline therapy, it is impossible to obtain informed consent as the patients affected by the editing are the embryo and future generations.

5. Limited Knowledge of the Functions of the Genes

Scientists know functions of limited genes, and worst is in some cases, scientists don’t know whether a particular gene is performing more than one function

6. Regulatory Concerns

Developing  appropriate regulations and  guidelines  to govern  the  use of genome editing  technologies  presents  a  challenge to  ensure responsible and  safe applications

7. Others

• It might lead to designer babies & the commodification of children.
• It can be used in biological warfare.
• Recreation of extinct species can lead to disasters.
• If a wrong DNA segment is inserted and if it gets expressed, it can cause new diseases in human beings.

Side Topic: Gene Knock Out

A gene ‘knock out’ is a genetically engineered organism that carries one or more genes in its chromosomes that have been made inoperative.

Currently, four families of engineered nucleases (Molecular Scissor) are used: 

• Mega Nucleases
• Zinc Finger Nucleases
• Transcription Activator like  Effector based Nucleases (TALENs)
• CRISPR- Cas System (Most advanced & important)

CRISPR/Cas9 System of Germline Editing

• CRISPR Cas 9 technology works like a cut-and-paste mechanism on DNA strands. The DNA strand identifies the specific location of the genetic codes that need to be changed or “edited” and then, using the Cas9 protein, which acts like a pair of scissors, that location is cut off from the strand. Once the DNA strand is broken, it has a natural tendency to repair itself. During the auto-repair process, Scientists intervene by supplying the desired sequence of genetic codes that binds with the broken DNA strand.
• Nobel Prize for Chemistry in 2020 was awarded for discovering the CRISPR Cas9 scissor.
• It is a revolutionary technique for Gene Editing with very high efficacy 
  • CRISPR: It is the mechanism that Bacteria uses to protect themselves from viruses. In this system, DNA is plucked out of Virus and inserted in little bits into the bacterium’s chromosome. In this way, Bacteria records the viruses it has been exposed to so that cells are protected from those viruses in the future. 
  • Cas 9 is a cutting enzyme. 

Stage 1

Guide RNA is shepherded with Cas 9 System 

• RNA is used to guide Cas 9 to the targeted position.
• Cas 9 is used to make a cut. 

Stage 2

• Cas 9 locks onto DNA &
  unzips it (both strands are divided).

Stage 3

• Cas 9 snips the DNA, creating a break in both strands.

Stage 4

• The DNA will repair itself using an inbuilt repaid mechanism using a piece of single-stranded DNA injected into the cell that binds itself with the broken DNA strand.

Why it is revolutionary

• It is cheaper (than already existing gene-editing technology).  
• It has very high efficacy.

Uses/ Applications

Its applications are immense, and it has made the designer baby a reality. Since it will have a wide range of ethical and social implications, inventors Jennifer Doudna and Emmanuelle Charpentier have called for Moratorium until proper consensus on its use is made. 

• Cure to diseases: CRISPR Cas-9 technology is used to treat many incurable diseases. It includes the cure for Sickle Cell Anaemia, diabetes, inherited eye diseases, and various types of cancers. E.g., in 2023, the US has approved CRIPR based gene therapies (named Casgevy and Lyfgenia) to treat patient with Sickle Cell Disease. Additionally, clinical trials are going on to treat diseases like HIV/AIDS, diabetes, cancer etc.
• Controlling number of mosquitos: Scientists have used the CRISPR technique to produce sterile male mosquitos of species that are responsible for spreading diseases such as malaria, dengue, zika etc. 
• Some scientists call for bringing extinct species back to life using this technology, like the Oxford Universities project on reviving Mammoth.

Issues with the Technology

• Designer Babies: Bioethicists fear abuse of gene editing by the private sector, preying on a parent’s desire to create a perfect child. In 2018, a Chinese researcher disclosed that he had altered the genes of a human embryo to prevent the infection of HIV. It was the first documented case of creating a ‘designer baby’, and it caused widespread concern in the scientific community.
• Issue of Informed Consent: Bioethicists have also raised the concern that it is impossible to obtain up-to-date consent for germline therapy because the patients affected by the edits are the embryo and future generations.
• Inclusivity Issue: Only wealthy people will be able to afford this technology, increasing existing disparities and creating another class of haves and have-nots.
• OffTarget  Effects: CRISPR Cas9 can sometimes edit unintended locations in the genome, leading to potential genetic alterations with unknown consequences.

The Stem Cells are the class of undifferentiated cells that have the ability to differentiate into specialized cell types.

Stem cells should be:

1. Undifferentiated cells having the ability to divide & differentiate themselves into specialized cells
2. It has the capability of self-renewal, i.e. reproducing itself

1. Embryonic Stem Cells

• They are derived from the embryo.
  • Humans reproduce sexually, i.e. need sperm and eggs.
  • The sperm fuses with the egg to form a fused product called Zygote. This cell divides itself to form different organs like eyes, heart, lungs etc., i.e. one cell is capable of producing an organism.
  • Hence, embryonic cells have the ability to differentiate themselves into different specialized cells.
• They are Totipotent, i.e. can become any specialized cell & organ.

2. Non-Embryonic /Somatic/ Adult Stem Cells

• Adult Stem Cells exist throughout the body after embryonic development. They are found inside the different tissues such as the brain, bone marrow, blood, blood vessels, Skeletal muscles, skin & liver.
• They remain in a quiescent or non-living state for years until activated by disease or tissue injury.
• They can divide or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerate the entire organ.
• Generally, adult stem cells are limited in their ability to differentiate based on their tissue of origin. 
• Adult stem cells are rare in mature tissues. Hence isolating these cells from adult tissue is challenging, and methods to expand their numbers in cell culture have not yet been worked out.

3. Induced Pluripotent Stem Cells (iPSCs)

• Adult cells that have been genetically reprogrammed to an embryonic stem cell-like state.

• Stem cells are generally derived from embryos, as adult stem cells are difficult to extract. But human rights advocates view this as equivalent to murdering a child.
• It was also against the conservative Christian beliefs and was vehemently opposed, especially in the USA. Republican governments were totally against this as they favoured promoting Christian ethics.

Converting ordinary cells to Induced Pluripotent Stem Cells – Gurdon & Yamanaka

• A single cell in the form of a Zygote formed after fertilization of egg and sperm differentiates to specialist cells like heart cells, liver cells, skin cells etc. Earlier, it was thought that this natural process was irreversible.
• But Gurdon and Yamanaka identified the genes to make any cell pluripotent and also showed that cells can be programmed to any specific cell like Bone Marrow or heart cell.
• It solved the issue of killing embryos to get Stem Cells.

• Ethical concerns: Ethical dilemmas in using stem cells involve the destruction of human embryos to obtain stem cells. In the USA, Christian values against the destruction of embryos stymied the research in stem cells.
• Efficacy of Stem Cell Therapy: iPSCs don’t have 100% efficacy, and in many cases, reprogrammed cells can result in cancerous cells by rapid division
• Inclusivity issue: Stem Cell therapy is costly, and the poor can’t afford it. Hence, it is not inclusive.
• Graft versus Host  Disease  (GVHD): Stem  cell  transplants  carry  the  risk  of  GVHD (although very low),  where  the  transplanted cells  recognize the  recipient’s  body  as  foreign  and  attack  healthy  tissues.
• Infections: Patients  undergoing  stem  cell  transplants  are  susceptible  to  infections  due  to  the  weakening  of the immune system.

• Western Countries have strict regulations and restrictions on the use of Stem Cells, but no such regulation was earlier present in India. Due to a lack of regulations and cheap treatment, many terminally ill patients were coming to India for treatment.

• In 2018, the Ministry of Health and Family Welfare proposed to amend the Drugs and Cosmetics Act, 1940, to bring Stem Cell and Stem Cell-based products under legal regulation. Under the amendments, Stem Cells and substantially altered products will be treated as drugs. Therefore, they will have to seek the regulator’s approval (Drug Controller General of India) before being marketed.

• Various ICMR Guidelines
  1. ICMR’s National Guideline for Stem Cell Research in 2017.
  2. Stem Cell Use Ethical Guidelines by ICMR  

• MoUs
  1. Indo– Japan Stem Cell Research Collaboration
  2. India – UK Stem Cell Research
  3. Research Centre: DBT Centre in Bangalore is dedicated to Stem Cell Research (In-STEM).

• GMOs are organisms whose DNA or genetic makeup has been altered using various techniques of genetic engineering. 
• In 1982, the first genetically modified crop, i.e. GM Tobacco, was produced. GM foods have been sold in the market since the early 1990s. 
• Genetic Modification develops specific traits in crops like:
  1. Herbicide resistance 
  2. Viral resistance 
  3. Pest resistance 
  4. Fungal and bacterial resistance 
  5. Slow ripening 
  6. Quality improvement – protein and oil
  7. Value addition – vitamins, micro and macro elements 
• GM plants are developed by private companies and public research institutions like International Maize and Wheat Improvement Centre (public research institution) and Monsanto (an American private company).

Herbicide Resistant Crops

• GM varieties of crops like soybean, maize, canola etc., have been developed, which are resistant to herbicide Glyphosate. Hence, it simplifies the weed control by Glyphosate application. (Note: Glyphosate herbicide is produced by Monsanto (of USA) under the trade name ‘Round up’.)
• Gene has been inserted into DMH-11 (Mustard) which makes it resistant to herbicide named Basta. 

Insect Resistant Crops

• GM crops such as Bt Cotton and Bt Brinjal are insect resistant because Bt genes can produce insecticidal toxins to the larvae of moths and butterflies, beetles, cotton bollworms, Lepidopberan insects (damages brinjal) and gadflies.

Flavr-Savr Tomato

• It was the first GM crop that was granted permission for human consumption. 
• It was produced by an American MNC named Calgene.
• Through genetic modification, the ripening process of the tomato was slowed down, thus preventing it from softening and increasing the shelf life.

Biofortification

• Golden Rice is the Genetically Modified Variety of Rice that can accumulate -carotene in the endosperm. Beta-Carotene is the precursor of Vitamin-A. It can be used in areas with Vitamin-A deficiency (which leads to night blindness).

GM Rubber

• GM Rubber was developed at Kerala based Rubber Research Institute of India (RRII) and was planted in the outskirts of Guwahati. It has additional copies of gene MnSOD which is expected to handle severe cold conditions during winter in North-East India.

Others

• Scientists in India have developed strains of Sub-1 rice, which are much more resistant to flooding.
• CSIR has developed (truly) Blue Rose using the gene from pansy (variety of flowers).
• The University of Texas has produced cotton with edible seeds by reducing its toxicity levels, thus converting cotton into an important food source. 
• Tearless Onions have been produced by removing genes that synthesize sulphur compounds which act as tearing agents.

Note: Indian government has allowed the commercialisation of only one GM crop, the BT Cotton with the Cry 1 Ac gene (Bollgard I).

Monsanto 

• It is an American MNC working in the field of applying biotechnology to agriculture.
• It is the leading producer of herbicide Glyphosate (Round-Up).
• Monsanto was the first company that create a biotechnology business model revolving around the company’s patent rights. 

MAHYCO

• MAHYCO = Maharashtra Hybrid Corporation
• It was started in 1964 and is headquartered in Jalna (Maharashtra).
• MAHYCO has developed a large number of high-quality hybrid seeds.
• MAHYCO also collaborates with academia and industry, and its association with Monsanto to produce BT cotton seeds using BT Technology of Monsanto since 1998 is such an example. 

• In 2018, FSSAI released Food Safety and Standards (Labelling and Display) Regulations, making it mandatory to clearly state on the label if the packaged food contains GM ingredients. 
• Any food will be considered GM food if it contains 5% or more GM ingredients. 

• Terminator Gene is the genetic code inserted in the DNA of the seed that makes the seeds harvested in the yield sterile. Hence, the farmer can’t use the harvested crop as seed and have to buy new seeds every season. 
• CoP-8 of the UN Convention on Biodiversity (CBD) has prohibited the use of terminator genes. Consequently, India has passed a law banning this technology. 

• Hybridisation is the technique or method involving cross-pollination among two different varieties to bring their desired characters together into one progeny called Hybrid.  
• Hybridisation is the common method of creating a genetic variation to get improved varieties. Humanity has used this technique since pre-history. 

Examples of Hybrid Crops

• Seeds produced during the Green Revolution like Sonalika and Kalyan Sona (Dwarf varieties of wheat) and IR-8 (dwarf variety of rice) were hybrids. 
• Case of Hybrid Sugarcane for North India:   

Other Hybrid Seeds include

What is BT (Bacillus Thuringeinsis) ?

• Bt refers to Bacillus Thuringenesis. It is a gram-positive soil-dwelling bacterium.  This bacteria produces more than 200 toxins that have insecticidal properties wrt the larvae of moths and butterflies, beetles, cotton bollworms and gadflies but are harmless to other life forms.

• When specific genes from Bacillus Thuringenesis are introduced into the native cotton and brinjal varieties, it starts to produce toxins that destroy the digestive system of bollworm and stem borers. 

Analysis: Bt Cotton in India

Positive Effects

The government approved to grow Bt Cotton in 2002 & as a result, India witnessed a great revolution in the cotton sector, not seen for another crop.

• The yield of cotton increased due to the effective control of bollworms. After the introduction of Bt Cotton, India saw a rise in cotton production by 178%. India has emerged as the most significant global cotton player and is presently the largest cotton producer (surpassing China).
• A significant reduction was witnessed in the use of insecticide in the cultivation of Bt cotton. 
• The cost of cultivation was also reduced as artificial insecticides were not required. 

Issues

• The issue is increasing farmer suicides in Karnataka and Vidarbha region.  Farmers are using expensive GM seeds in drought-prone areas.
• There are other problems too –
  1. High input cost of seeds, 
  2. Genetic erosion of local varieties, 
  3. Farmer’s dependence on private seed companies whose sole aim is profit maximization. 
• Recently, cotton plantations in various parts of the country have been hit due to the infestation of Pink Bollworm (PBW). Following reasons are responsible for this :
  1. Absence of crop rotation.
  2. Not growing 20-30% regular cotton along with BT Cotton.

• DMH-11 Mustard is produced by the Delhi University’s Centre for Genetic Manipulation of Crop Plants. 
• DMH-11 is a GM Mustard Hybrid.
• It is India’s first indigenously developed GM food crop.
• In October 2022, GEAC approved the environmental release of GM mustard. Later, release of the GM Mustard was put on hold after Supreme Court intervention. 

Justifications for allowing DMH-11

• In an ordinary situation, hybrids can be obtained by cross-pollination of two varieties of the same species. But the case of Mustard is different as natural hybridization isn’t possible in Mustard because its flowers contain both female (pistil) and male (stamen) reproductive organs. Hence Genetic Modification is the only way to make High Yielding Variety (HYV).
• Moreover, India is importing 15 million tonnes of edible oils. Hence, there is a need to raise domestic crop yields.  
• Cotton-seed oil from Bt cotton is already used in India and is perfectly safe. Cotton-seed oil is the second largest produced edible oil in the country (1.4 million tonnes) after Mustard (2 million tonnes).
• India is already importing GM oil: India imports 3 million tonnes of soyabean oil annually, predominantly Genetically Modified.  
• The developer is a government-funded institution (Centre for Genetic Manipulation of Crop Plants at Delhi University), as opposed to BT cotton, which is the intellectual property of multinational, namely Monsanto.

Issue

• Another gene has been inserted into DMH-11 which makes it resistant to herbicide named Basta. It will compel farmers to use specific herbicides and be dependent on one company (i.e. Bayer) having a monopoly over pesticides.
• Unknown Longterm  Effects: The  longterm ecological and health effects of GM Mustard are still not fully understood, raising concerns about potential risks and unintended consequences.