M2L1: Biotechnology and its applications

Charles Darwin, a great British Scientist. Have you heard of him? I am sure you do. Let us start with his theory. Darwin started his journey on a ship to sail around the world. While returning to his country, he stayed on a group of Islands known as Galapagos. This island is close to Latin America and is owned by Republic of Ecuador.

There he noticed something unusual. On the group of those six islands, he found that there were sparrows, all of them looking almost alike except one feature that differentiated them. It was their beak. He inferred that, since all the sparrows look almost alike, they belong to the same family of species. But the billion-dollar question, that sparked in his mind was, why do their beaks differ from each other?

With this, he started investigating to finally come out with a brilliant theory, ‘The origin of the species by means of natural selection’. He realized that while all of them belong to the same family, their beaks differed from each other since all of them lived in different environments, where their diet differed from each other. The ones who ate insects had short beaks, while the ones that sucked nectar had long beaks while the one that fed on seeds had wide beaks.

He wrote in his book,

“Species change, species evolve from the same group.

But…
why do they change?

So as to live & defend themselves against nature.”

Darwin, worked on one of the most revolutionary theories of his time. But he always had a question, apart from the theory that he presented to the humanity. After realizing that species change, species evolve, he asked himself. “What passed these characteristics from one generation to another??”

He could not live long to get an answer to this question

Then came a person Gregor Mendel. He did a series of crosses (cross pollination) on selected pea plants with contrasting characteristics such as

1.    one with stem length that was tall and other that was dwarf

2.    one possessing flower position that was axial and other that was terminal

3.    one possessing pod shape that was inflated and other that was constricted

4.    one possessing pod color that was green and other that was yellow

5.    one possessing seed shape that was round and other that was wrinkled

6.    one possessing cotyledon color that was yellow and other that was green

7.    one possessing seed coat color that was grey and other that was white.

Mendel cross-pollinated the pea flowers by removing the male reproductive organs from one plant flower and fertilizing the female reproductive organ on another plant. When doing crosses, the original pair of plants is called the P or parental generation. Their offspring are called the F1 or first filial generation

Much to his surprise, when Mendel crossed two plants with different traits, only one of the traits showed up in the offspring F1. The F1 peas carried round seed shape, yellow seed color, gray seed coat, smooth pod shape, green pod color, axial flower position, and tall plant height.

Mendel drew two conclusions:

1. An individual's characteristics are determined by factors that are passed from one parental generation to the next. Today we call these factors genes. Different forms of a gene are called alleles. For example, everyone has a gene for eye color. The different alleles for eye color might be blue, brown, green, and hazel.

2. Principle of Dominance: states that some alleles are dominant and others are recessive. An organism with a least one dominant allele for a particular form of a trait will exhibit that form of the trait. The recessive allele for a particular form of a trait will exhibit that form only when the dominant allele for the trait is not present.

Now Mendel had one more question. F1 possessed those traits viz. round seed shape, yellow seed color, gray seed coat, smooth pod shape, green pod color, axial flower position, and tall plant height. This means that these are the dominant alleles for pea plants. But the plant should ideally carry the recessive allele that it gained from one side. Where did this gene with recessive allele go?

Mendel allowed this F1 generation to breed with itself by self-pollination. He found that recessive traits showed up again in the F2 generation. This means that the F1 plants did carry the recessive allele but the dominant allele had masked the corresponding recessive allele in the F1 generation.

In the year 2004, scientists started looking at genes known to regulate bone and cartilage development in the face. Research on the gene activities between the small-beaked v/s the large-beaked finches proved that Darwin’ finches had two genes that regulated their beaks 1.    BMP4 protein gene that controls beak depth and width and is responsible for the broader, heavier beaks found in the seed-eating ground finches (ground finch). 2.    CaM gene that controls beak length and is responsible for the longer beaks that cactus finches use to probe for nectar in cactus flowers and fruit.

What does this mean for UPSC?

I will try to explain this with an example.

Let us assume, that the father has a brown eye color and the mother has blue eyes. In the next generation, it was found that the son/daughter displays brown eye color because in this case, the gene for brown allele is found to be dominant. Does this mean that gene responsible for blue allele is absent? Nopes. Since it is recessive, the dominant has masked its effect. Therefore, it is still present and hidden.

Okay now say, one of the parents is carrying one defect. Let us assume Thalassemia minor. The other parent is healthy and doesn’t carry the defect of this type. What is more likely? Will the next generation carry Thalassemia minor or major? Chances are less than 25% that the kid will carry this defect. This is because, the healthy allele (gene that is without any defect) has become dominant and masked the effect of recessive allele (that is carrying Thalassemia minor, a hereditary disorder)

Now let’s take another case. Both the parents are carrying Thalassemia minor. Now will the next generation carry this defect? Yes or No. Studies prove that the chances are more than 75% because the kid may be inheriting defective gene from both the sides. Hence in either case, whichever defective gene gets dominant, will show its effect and carry forwarding this problem.

So, should we undergo DNA profiling before getting married to see if the best genes from both the side are dominant in our next generation? I will leave that answer for you. We will return back to our main topic.

Why does the Indian culture discourage marriages among first cousins? (first cousins are those who are directly from the generation of your maternal aunt/ maternal uncle or paternal aunt/paternal uncle?

To understand this, let us go back to the same example that we studied before few minutes

When the kid born through the couple among which, either one is carrying Thalassemia minor (can be only mother or only father), the chances of kid inheriting the same is less than 25%. This doesn’t mean that the recessive allele (defective gene) is altogether removed. It means that it may be present but its effect is completely masked by dominant allele (healthy gene without any mutation responsible for Thalassemia)

 Now say this couple (P1) has given birth to a boy and a girl (we will call them F1 (first generation)). Both of them are healthy and free from Thalassemia. However, although both of them are healthy, chances still exist that both of them are carrying the recessive allele although the effect is not visible as the dominant allele has masked it.

Now both the son and daughter got married to some other family. The son got a beautiful wife and the daughter got married to handsome young man. Almighty gifted both of them with a son and a daughter. (We will call them second generation (F2)) and they are first cousins. While both are healthy, probability still exists that the two are carrying the recessive gene although the effect is completely masked. When they get married, the next generation may inherit recessive-recessive from both the sides. Although the chances are meagre, but it cannot be completely neglected. And therefore, this may lead to hereditary disorders in the next F3 generation, born by marriage among first cousins of F2 generation.

If this thing holds for humans, does it hold true for animals? 100% yes. If the population of species has dwindled very fast, and very few numbers of animals are left in that population of species, there are chances of inbreeding among them. This makes the coming generation more vulnerable to genetic disorders.

So, what should we do, to prevent this? Recall the fact that the genes are located in DNA double helix/ DNA ribbon.

When the population of species gets dwindles, and they become endangered or critically endangered, the wildlife staff first do the DNA profiling of each and every individual. This helps to identify, which individuals are more susceptible to certain diseases based upon their genetic makeup. Wildlife staff then use this DNA profile of individual animal to establish potential breeding partners in their captive breeding programs to minimize the chances of recessive gene getting carry-forwarded in the next generation. This helps to improve the chances of producing a healthy offspring to preserve threatened population.

The International Fund for Animal Welfare (IFAW) campaign group is now using this DNA profiling in an intelligent way. They are using these tests to provide evidence that Japan and Korea had engaged in the illegal killing and sale of meat from endangered whales. Can India use this to check upon illegal trade of wildlife that are covered under CITES?

What are the other applications of DNA profiling?

Usually, there is a 50% match between the child’s DNA and his/her father or mother. Between siblings (real brothers and sisters), their DNA match can range anywhere between 25% to 75%. In case of monozygotic twins, their DNA match would show a 100% match. By examining this DNA sequence, it helps to identify the relation between two people.

 

Similar to the industrial barcodes, short gene segments – known as DNA barcodes – are unique for each species. The ultimate goal of DNA barcoding is to build a publicly accessible reference database (taxonomy/catalogue) with species-specific DNA barcode sequences. Such a reference library will offer a rapid, reliable and cost-effective tool for. species identification of all animal species (i.e. birds, butterflies, fish, flies, etc.), plants and fungi with various applications.

This can be used

[1] in paternity testing.

a.            to can be used to identify the babies if ignorantly exchanged in hospital wards

b.            to know the true parental lineage of the kid

c.            to solve inheritance dispute

d.            To trace lost children. India is a signatory to UN Convention on the Rights of the Child. While, the government has launched “TrackChild” and “Khoya-Paya” portal to trace the missing children & stop child trafficking, DNA fingerprinting can increase the efficiency of our efforts to reunite lost children with their families.

e.            identification of identical twins using DNA fingerprinting

[2] ancestry & racial identification of people belonging to the same family.

a.            to solve immigration cases wherein the person claiming to be a relative to the real citizen is true or not

b.            In case of wildlife, this can be used for pedigree analysis & to assess the impact of the fragmentation of a species caused by the loss of habitat.

Conducted from 1990 to 2003, The Human Genome Project (HGP) is an international scientific research project with the goal of determining the sequence of chemical base pairs which make up human DNA, and of identifying and mapping all of the genes of the human genome. It is the largest and most expensive single project in the history of biology mapping, 20,000+ genes of the human genome from both a physical and functional standpoint, creating a wealth of scientific data and $1 trillion in economic returns. Now, scientists have announced the most ambitious effort of its kind, the Earth Bio Genome Project (EBP). Whereas the earlier Human Genome Project was restricted to a single species – humans – the EBP will study 1.5 million forms of life. It will aim to sequence, catalogue and categorize the genomes of all of Earth's eukaryotic biodiversity over a period of ten years. Eukaryotic species (animal, plant, protozoa and fungi) are organisms whose cells have a nucleus enclosed within membranes, unlike prokaryotes, which are unicellular organisms that lack a membrane-bound nucleus, mitochondria or any other membrane-bound organelles (Bacteria and Archaea). Currently, fewer than 3,500 – or about 0.2% – of all known eukaryotic species have had their genome sequenced, with less than 100 at reference quality. Sequencing all known eukaryotic genomes could revolutionize our understanding of biology and evolution, as well as bolstering efforts to conserve and restore the Earth's biodiversity. As a part of this ambitious efforts, scientists have finished the DNA sequencing of genome of koala bear, wheat and sugarcane genome.

[3] identification of a living organism whose personal information for identification is not easily available

a.            during criminal investigation of the cases involving rape and murder

b.            to identify the dead whose body is completely partially mutilated or through his/her skeletal remains.

c.            during disasters where it becomes hard to identify the victims. DNA profiling can be used identify the relatives of those victims.

The government has come out with DNA profiling bill 2018. What are the features and controversies related to it?

[4] This will also help to minimize antimicrobial resistance. Every person has a different DNA makeup which makes him/more more/less susceptible to the same set of drugs. DNA profiling will thus act as a gateway for precision medicine, wherein the patient will be administered only selective drugs to maximize the therapeutic efficacy.

Genome Asia 100k is a mission driven non-profit consortium collaborating to sequence and analyze 100,000 Asian individuals’ genomes to help accelerate Asian population specific medical advances and precision medicine.

[5] DNA profiling (also known as gene sequencing) will help us usher into a new age for medicine to diagnose & cure, any inherited disease using genome editing techniques like CRISPR.

[6] DNA profiling is a ladder to Bioinformatics & Genomics. Through engineering tools like Information Technology, Computation & Analysis, it can help to discover the role & function of each gene. Such genes are known as genetic markers. This gene may be responsible for some disease tolerance or it can also be responsible to transmit some disease.

This finds an enormous application in fields like

a.    increased production and profitability of agriculture & food products by decreasing the loss from disease and pests and improvement in traits like insect resistance, herbicide tolerance, drought tolerance, enhanced ethanol & fiber production, increased omega-3 fatty acids content, increased oleic content and essential nutrients through biofortification, better colors through increased proportion of pigments etc. This emerging field is called agricultural biotechnology and is also recognized as agricultural revolution 2.0 (not to be confused with evergreen revolution).

b.    to improve size and flesh contained within the fishes within fisheries & aquaculture.

c.    Healthcare For e.g. it can help in the discovery of a vaccine by predicting the 3D structure of the protein molecule & it’s associated function in the virus or bacteria, that is causing the disease. 

1.            Recently, CSIR has developed a salt tolerant rice ‘pokkhali jyothi’ using Saltol gene. This rice can grow on lands where saline waters of ocean and sea have intruded. 2.            CSIR has also developed a new variety of rice, ‘Muktshree’ that doesn’t absorb arsenic. This will help to reduce the problem of arsenic accumulation among people of West Bengal.

Can Biotechnology be used for management of wastes and purifying water?

Waste can be divided into following types

1.    e-waste

2.    Urban solid waste

3.    Medical waste

4.    Plastic waste

5.    Agricultural Waste

a)    In its report, ‘Preventing disease through healthy environments, towards an estimate of the environmental burden of disease’, WHO notes that 8-9% of all the deaths were due to toxic waste that is also found in e-waste.

b)    In the same report, WHO notes that an estimated 24% of the disease burden (that leads to a loss of healthy life) and an estimated 23% of all deaths (that contribute to premature mortality) was attributable to environmental factors.

c)    According to the Global Burden of Disease Study (GBD) published in the medical journal The Lancet, India ranks 154th among 195 countries on the healthcare index. Hence, improvement in solid waste management & hazardous waste including e-waste will indirectly help us improve our ranking in SDGs by provide good health & environment to our people as well as help us reduce mortality rates.

Problems associated with improper management of solid waste

1.    Due to decomposition & rotting, landfill sites are a source of Vector Borne Diseases (dengue, chikungunya, malaria, japanese encephalitis etc.).

2.    During run-off in monsoons, this solid waste pollutes water bodies.

3.    Leaching from organic waste pollutes ground water. Leads to deaths of infants due to diarrhea.

4.    Methane gas, released due to decomposition of solid waste pollutes the environment

5.    Toxic fumes due to internal burning & accidental fires, pollute environment & the health of the people, living in adjacent neighborhood.

Conventional methods of solid waste management include thermal conversion that are expensive & also produce toxic particles like dioxins & furans. These include

·         Pyrolysis

·         Incineration

·         Conventional Gasification

·         Plasma Arc Gasification

·         Hydrothermal Carbonization

·         Hydrothermal Oxidation

Environmental biotechnology (also referred as green technologies) is the branch of biotechnology that addresses these environmental problems, such as the removal of pollution, renewable energy generation or biomass production, by exploiting biological processes. This offers us low cost, low capital-intensive techniques that can be carried on site.

Opportunities for India in the field of Biotechnology

India is a home to 130 crore population that is still growing. (census 2011 – 125 crore). Pressures that this growing population is putting on land resources & corresponding degradation of environment.

Based on the application, it can be divided into following segments

Red	Biotechnology that is known for biomedical products related to health, medical and diagnostics. For e.g. producing insulin for diabetic patients, developing drugs to treat cancer. When the drug products are manufactured in, extracted from, or semi-synthesized from biological sources, they are referred to as bio-pharmaceuticals and the specific process is referred to as bioprocess (that uses complete living cells or their components for e.g., bacteria, enzymes, chloroplasts to obtain desired products). The first such substance approved for therapeutic use was recombinant human insulin
Yellow	Biotechnology known for improving food & nutrition security. This is already under use to increase the shelf life of the crops, omega 3 & omega 6 fatty acids, oil content in oil seeds, increasing resistance to droughts, diseases, pests & salinity. For e.g. Golden rice, Bt Cotton etc.
Blue	Biotechnology in aquaculture, coastal and marine areas to increase food security & promote livelihoods of local communities
Green	Biotechnology known for agricultural and environmental products. Can be used to develop Biofuels, Biofertilizers, Bioremediation, Geomicrobiology & eco-friendly fibers.
Brown	Biotechnology for reclamation of arid and desert wastelands into fertile
Grey	Classical Fermentation and Bioprocess Technology to make wines, beers & distillery products
Gold	Bioinformatics, Nanobiotechnology to treat cancer
White	Gene-based Bioindustries that make vaccines

The National Biotechnology Development Strategy (2015-2020)

NBDS 2015-2020 focusses on tapping the potential of Biotechnology to promote Make in India program and using the sector to promote Knowledge based economy

The National Biotechnology Development Strategy focusses on developing the Indian Biotechnology sector into a 100 Billion $ industry by the year 2020. It emphasizes on development of high-end human & physical capital & an infrastructure to benefit sectors like development of clean energy, Waste Management, Agriculture & Climate Change.

The renewed mission is to:

§  Provide impetus to utilizing the knowledge and tools to the advantage of humanity,

§  Launch a major well directed mission backed with significant investment for generation of new biotech products,

§  Empower scientifically and technologically India’s incomparable human resources,

§  Create a strong infrastructure for R&D and commercialization, and

§  Establish India as a world class bio-manufacturing hub.

The ten guiding principles of the ‘National Biotechnology Development Strategy: 2015−2020’ are as follows:

§  Building a skilled workforce and leadership

§  Revitalizing the knowledge environment at par with the growing bio-economy

§  Enhancing research opportunities in basic, disciplinary and inter-disciplinary sciences,

§  Encouraging use-inspired discovery research,

§  Focusing on biotechnology tools for inclusive development,

§  Nurturing innovation, translational capacity and entrepreneurship,

§  Ensuring a transparent, efficient and globally best regulatory system and communication strategy,

§  Biotechnology cooperation by fostering global and national alliances,

§  Strengthening institutional capacity with redesigned governance models, and

§  Creating a matrix of measurement of processes as well as outcome.

WHAT IS KNOWLEDGE-BASED ECONOMY? The knowledge-based economy or innovation driven economy is the one that uses Knowledge as a product to drive its economy.

Based on industry analysis of the biotech sector and inputs from experts, the following thrust areas are selected for concentration:

§  Diagnostics

§  Therapeutics

§  Pharmacogenomics

§  Bioinformatics

§  Agriculture biotechnology

§  Industrial biotechnology

§  Marine biotechnology

§  Forest and Environment-focused biotechnology

§  Research in all related areas of biotechnology

The above key elements would be implemented in collaboration and partnership with other ministries, departments of state governments and international agencies towards achieving the following goals:

§  Making India ready to meet the challenge of achieving US$100 billion by 2025

§  Launching four major missions: healthcare, food and nutrition, clean energy and education

§  Creating a technology development and translation network across the country (5 new clusters, 40 biotech incubators, 150 TTOs, and 20 bio-connect centers) with global partnership, and

§  Strategic and focused investment in building the ‘human capital’ by creating a ‘Life Sciences and Biotechnology Education Council’.

Role of BIRAC

The Department of Biotechnology under the Government of India has established Biotechnology Industry Research Assistance Council (BIRAC), a not-for-profit Public Sector Enterprise. It acts as an Interface Agency to strengthen and empower the emerging Biotech enterprise to undertake strategic research and innovation to address nationally relevant product development needs. It aims to

§  Foster innovation and entrepreneurship

§  Promote affordable innovation in key social sectors

§  Empowerment of start-ups & small and medium enterprises

§  Contribute through partners for capability enhancement and diffusion of innovation

§  Enable commercialization of discovery

§  Ensure global competitiveness of Indian enterprises

However, the following issues needs to be addressed to realize the targets mentioned in this document