Biopharming

biopharming plants and animal both

1. BIOPHARMING II MSc MICROBIOLOGY(3 RD SEM) ANUSHREE GUPTA, G BALA TRIPURA, MAIBAM YAISANA CHANU, SHALOYANA MOHANTHY, URVI SHARMA

2. INTRODUCTION Pharming , a portmanteau of "farming" and "pharmaceutical. Biopharming is the production and use of transgenic plants and animals genetically engineered to produce pharmaceutical substances for use in humans or animals. It often involves the insertion of gene constructs derived from humans. The products of pharming are recombinant proteins or their metabolic products. Recombinant proteins are most commonly produced using bacteria or yeast in a bioreactor, but pharming offers the advantage to the producer that it does not require expensive infrastructure, and production capacity can be quickly scaled to meet demand, at greatly reduced cost. [ For example, genetically modified yeast, bacteria, and animal cell cultures have for some time been used to produce pharmaceutical substances in enclosed bioreactor systems, but are generally not included in the definition of biopharming.

3. On the other hand, plant cell cultures, a newer development but also involving enclosed bioreactors, are typically included together with whole-plant methods in plant biopharming While animals are also being genetically modified to alter their nutritional composition, to make them better models for human disease, and to provide more compatible organs for transplantation into humans, these are typically excluded from the definition of biopharming.

4. HISTORY Biopharming has been carried out experimentally for more than 20 years. Biopharming has not been widely discussed in the popular media, even though it has been implicated in several genetic-modification controversies. The animal who became known as Stier Herman (Herman the Bull), the first transgenic bovine, was a biopharm animal produced in the Netherlands in 1990 and modified with the human gene for producing lactoferrin. The first recombinant plant-derived protein (PDP) was human serum albumin, initially produced in 1990 in transgenic tobacco and potato plants. Open field growing trials of these crops began in the United States in 1992 and have taken place every year since. While the United States Department of Agriculture has approved planting of pharma crops in every state, most testing has taken place in Hawaii, Nebraska, Iowa, and Wisconsin.

5. YEAR DEVELOPMENT REFERENCE 1986 First plant derived recombinant therapeutic protein human GH in tobacco & sunflower A Barta, D. Thompson et al 1989 First plant derived recombinant antibody full sized IgG in tobacco A.Haitt,K.Bowdish 1990 First native human protein produced in plants – human serum albumin in tobacco & potato P.C.Sijmons et al 1992 First plant derived vaccine candidate- hepatitis B H.S.Meson, D.M.Lam 1995 Secretory IgA produced in tobacco J.K.Ma, A.Hatt, M.Hein et al 1996 First plant derived protein polymer artificial elastin in tobacco X. Zhang, D.W. Urry, H. Daniel

6. 1997 Commercial production of avidin in maize E.E.Hood et al 2000 Human GH produced in obacco chloroplast J.M.Staub et al 2003 Expression and assembly of a finctional antibody in algae S.P. Mayfield, S.E. Franklin et al 2006 Commercial production of bovine trypsin in maize S.L. Woodard et al

7.  By 2003 several PDP products for the treatment of human diseases were under development by nearly 200 biotech companies, including recombinant gastric lipase for the treatment of cystic fibrosis, and antibodies for the prevention of dental caries and the treatment of non-Hodgkin's lymphoma. I n 2006,Commercialized Plant made antibody and Plant-made vaccine were developed. Research is still being pursued by competing groups using a range of animals (large and small), outdoor plant production, indoor plant production, and plant cell cultures. The proponents of each argue that their platform has advantages in productivity, scalability, speed of response, safety of drug produced, cost, or suitability to particular conditions. A significant amount of this research is publicly funded.

8. INTRODUCTION TO PLANT BIOPHARMING Plant biopharming refers to the use of genetically modified plants to produce a wide range of pharmaceuticals and industrial products. Biopharming includes both crops in which the pharmaceutical is expressed, and the replication of seeds of such plants to enable commercial production. This involves insertion of a gene, which encodes a protein of interest, into an host organism. The host organism is grown to produce large quantities of the protein, which is subsequently purified. Plants such as tobacco, for example, can be genetically engineered to produce therapeutic proteins, monoclonal antibodies and vaccines to treat cancer, inflammatory diseases and other life-threatening or debilitating conditions. Plants are also used in production of various enzymes, hormones, interferons, structural proteins etc.

9. GENERAL PROCEDURE OF PLANT BIOPHARMING STEP 1: STEP 2: STEP 3: STEP 4: STEP 5: ISOLATION OF GENE OF INTEREST CONSTRUCTION OF TRANSGENE TRANSFER OF FOREING GENE INTO THE HOST SELECTION OF TRANSGENIC PLANT IDENTIFICATION AND ISOLATION OF THE PLANT TISSUE

10. HOW IS PLANT BIOPHARMING DONE ? There are various ways to genetically modify plants to turn them into m ini factories or “bioreactors” for biologic drug and commercial production. NUCLEAR TRANSFORMATION : This transformation involves the integration of foreign gene in the genome of a plant. Nuclear transformation allows to target proteins to various subcellular regions like endoplasmic reticulum, plastids, vacuole, apoplast, which facilitate correct posttranslational modification. PLANT VIRAL SYSTEM: Expression of recombinant protein done by a viral vector is a method for examining protein and its desired character in a plant. Virus infected plants are used to get antigens and antibodies with rapid onset of expression and more than one vector can be used in the same plant. The plant produces the high quantity of desired protein within 1-4 weeks of inoculation.

11. TRANSIENT EXPRESSION IN PLANTS: Fully grown plants, four to six weeks old, are immersed in the Agrobacterium suspension under vacuum pressure, allowing the Agrobacterium to penetrate the plant cells to introduce the genes of interest through a natural process, which alters the plant’s DNA and directs it to begin to manufacture (express) the protein. After the plants are treated in this manner, they grow for another week, generating biomass, and are the harvested and the protein material extracted and purified to make a biopharmaceutical drug. 

12. STABLE TRANSGENIC PLANTS: Stable transgenic plants are developed by stably altering the DNA of a plant’s nuclear or chloroplast genomes. Seed lines are then developed for continual propagation of plant biomass using traditional agricultural techniques and equipment. In the leaves of higher plants, each cell has as many as 100 chloroplasts, each of which contains up to 100 copies of the genome. Thus, by inserting a transgene into the chloroplast genome,one can greatly amplify the gene and produce large amounts of the corresponding protein.

13. METHODS OF GENE TRANSFER IN PLANTS Two methods are used to transfer foreign genes into plants. U se of a plant pathogen called Agrobacterium tumefaciens: Agrobacterium tumefaciens causes crown gall disease in many species. This bacterium has a plasmid, that contains tumor-inducing genes (T-DNA), along with additional genes that help the T-DNA integrate into the host genome. Agrobacterium must first be “disarmed” by removing most of the T-DNA so that it does not make the plant sick leaving the left and right border sequences, which integrate a foreign gene into the genome of cultured plant cell.

14. GENE GUN: Gene gun fires gold particles carrying the foreign DNA into plant cells. Some of these particles pass through the plant cell wall and enter the cell nucleus, where the transgene integrates itself into the plant chromosome. Because both methods of gene transfer are fairly random, one must screen for the plant cells that contain the foreign gene.

15. PLANT BIOPHARMING IN AGRICULTURE The up- and down-regulation of desired genes which are used for the modification of plants have a marked role in the improvement of genetic crops. The role of genetic engineering in generating transgenic lines/cultivars of different crops is also to produce improved nutrient quality along with resistance and better yield. 1. Transgenic rice : a)  -carotene (Golden Rice), b) higher iron content, c) higher content of zinc etc. 2. Transgenic potato : a) gene from grain amaranth for high protein content 3. Transgenic maize : , a) higher content of lysine and tryptophan and b) nutritive value equivalent to that of milk. 4. GE coffee : Decaffeinated by gene silencing

16. HOW TO MAKE GENETICALLY MODIFIED CROPS STEP 1: STEP 2: STEP 3: STEP 4: STEP 5: TRANSFER OF DNA INTO A PLANT CELL GENE OF INTEREST IS TRANSFERRED INTO THE BACTERIUM TRANSFER THE NEW DNA TO THE GENOME OF THE PLANT CELLS . CHECKING FOR THE TRANSFORMANTS GROWN TO CREATE A NEW PLANT

17. PLANTIBODIES: ANTIBODIES PRODUCED IN PLANTS The term “plantibodies” describes the products of plants that have been genetically engineered to express antibodies and antibody fragments. P lants are being used as antibody factories (bioreactors), utilizing their endomembrane and secretory systems to produce large amounts of clinically viable proteins which can later be purified from the plant tissue. Antibodies, originally derived from animals, are produced in plants by transforming the latter with animal antibody genes P lantibodies have been shown to function in the same way as normal antibodies.

18. PRODUCING PLANTIBODIES STEP 1: STEP 2: STEP 3: STEP 4: STEP 5: STEP 6: INTRODUCE NEW GENES INTO A HOST THE TRANSFORMANT CELL IS THEN INTRODUCED INTO THE PLANT EMBRYO PROPAGATION OF THE PLANT IN THE OPEN FIELD EXTRACTION OF THE ANTIBODIES FROM THE PLANT TISSUE SELECTION OF TRANSFORMANT CELL PURIFICATION OF THE ANTIBODY

19. MONOCLONAL ANTIBODY PRODUCTION Introduction of gene of interest into the host transformed plants selected cultivated  in vitro regeneration of mature plants propagation of plant cells as a cell-suspension culture Purification of antibodies expressed in plants (affinity chromatography ) plant tissues must be homogenized Contaminants and toxins released mAb purified

20. PLANT BIOPHARMING IN VACCINE PRODUCTION Plant-based vaccines are recombinant subunit vaccine. PLANT BASED VACCINES DISEASE Hepatitis B surface antigen (HBsAg) (Tobacco Plant ) Hepatitis B Heat labile toxin B Subunit (LTB) Potato Tuber Diarrhoea Rabies virus glycoprotiein (RVG) (Tomato leaf) Rabies Cholera toxin B subunit (Tobacco leafs ) Cholera the antigen to be expressed as capsid proteins are selected proteins are expressed in plant tissues Agrobacterium tumefeciens and the antigenic gene to be inserted are mixed making a suspention host plant explant is exposed to the bacterial suspention cells are cultured and grown transformants are looked for and selected Plant regeneration ready to be used as vaccine.

21. ANIMAL BIOPHARMING Animal biopharming is defined here as the farming of transgenic animals genetically modified to produce “humanised” pharmaceutical substances for use in humans. Biopharming is also known as “molecular farming”. Organisms that have altered genomes are known as transgenic. Most transgenic organisms are generated in the laboratory for research purposes. Examples of types of animal biopharming currently being researched include cows, sheep and goats modified to produce the substance in their milk and chickens modified to produce the substances in their eggs. Biopharming is one of several methods that can be used to produce the class of drugs known as biopharmaceuticals.

22. STEPS INVOLVED IN BIOPHARMING STEP – 1 ISOLATION OF GENE OF INTEREST A typical Gene of interest must ideally contain promoters, enhancers, introns, transcription terminator, coding region. Techniques that are used to isolate the gene are PCR and RT-PCR. STEP – 2 CONSTRUCTION OF TRANSGENE

23. STEPS INVOLVED IN BIOPHARMING STEP-3 TRANSFER OF FOREIGN GENE INTO HOST DNA transfer can be done six different methods :- Direct microinjection Transposons Lentiviral Vector Sperm Pluripotent cells Somatic Cells STEP- 4 SELECTION OF TRANSGENIC ANIMAL This can be achieved by : - Probe hybridization PCR and RT-PCR

24. STEPS INVOLVED IN BIOPHARMING STEP – 5 IDENTIFICATION, ISOLATION, PURIFICATION OF RECOMBINANT PROTEINS Identification – This can be achieved by :- ELISA Immunoelectrophoresis Chromatography Mass spectrometry Isolation – The source material, whether blood serum, egg white, milk or any other tissue is manually isolated. Purification – This process must be carried out for the removal of pathogens.

25. ANTITHROMBIN IN MILK

26. Alpha 1 PROTEINASE INHIBITOR IN SHEEP The human lungs are constantly get affected by foreign particles such as dust, spores and bacteria. To prevent these, neutrophils releasing the elastase enzyme but this enzyme harmed the elastin in the lungs which maintains the elasticity of lungs. Human body releases a protein α1 proteinase inhibitor which has been successfully expressed in sheep. SPIDER GENES IN LACTATINGING GOATS - Two scientists at Nexia Biotechnologies in Canada spliced spider genes into the cells of lactating goats. The goats are used to manufacture silk, milk and secrete tiny strands from their body by the bucketful. By extracting polymer strands from the milk and weaving them into thread which is light and tough material that could be used to prepare military uniforms, medical micro sutures and tennis racket strings

27. SOME OTHER AREAS WHERE TRANSGENICS ANIMALS ARE USED :- Xenotransplantation Blood replacement Agriculture Disease control Toxicity testing Vaccine testing.

28. SOME FUNNY COMBINATIONS THAT WE CAN THINK OF

29. REGULATORY ISSUES Different regulatory agencies may have different cultures and be embedded indifferent power relations, which can pose problems for effective cooperation. Biopharming activity is generally being governed through regulatory frameworks developed forother purposes, and this can result in regulatory gaps and poor fit. For example, agriculture and medicines are typicallysubject to different governance regimes, yet biopharm plants and animals belong to both categories. Protecting the welfare of biopharm animals may also encounter category problems. For example,some jurisdictions distinguish between experimental animal trials and the use of animals inproduction. Many of the welfare problems associated with biopharming result from experimentation on embryos rather than the animals themselves, this possibly falls outside the regulation of animal trials.

30. Regulation of drugs produced through biopharming was also adapted rather than purpose-built. Biopharming animals may also fall outside the protections extended to farm animals, because they do not serve agricultural purposes. Good Manufacturing Practice (GMP) guidelines for biopharm drugs were originally modeled on those for animal cell cultures. These, however, are seen as too restrictive by those working with whole plants. BT corn approved for animal consumption found in products for human consumption.

31. WHAT ARE THE PURPOSE OF BIOPHARMING ? Biopharming is the cultivation of crops for a pharmaceutical purpose, giving them the ability to produce desired therapeutic proteins that are then extracted, purified, and used by the pharmaceutical industry to produce large-molecule, protein-based drugs.  Corn, rice, tobacco, and alfalfa are among the top candidates for being widely used in biopharming . Benefits – Faster and easier production of large quantities of vaccine proteins . Significantly lower production costs than current practices. Safer vaccine antigen production. Production (in plants) of proteins of greater complexity than is possible with microorganisms and to produce proteins that cannot be produced in mammalian cell cultures .

32. CONVENTIONAL TECHNIQUES All of the recombinant proteins produced and marketed to date are produced in bacterial, yeast, and mammalian cell culture systems. Most of the recombinant therapeutic proteins derived from transgenic livestock are in clinical trial phases. Bacterial culture Yeast culture Insect cell culture Mammalian cell culture Transgenic Plants

33. CONVENTIONAL VS TRANSGENIC CONVENTIONAL METHOD Higher cost . Limited post-translational modification. Low yield of recombinant proteins. Scale up is difficult. Isolation complexity. Aseptic environment required. TRANSGENIC METHOD Relatively lower cost. Almost all Post-Translational modifications. Higher yield of recombinant proteins. Scale up is highly efficient. Relative ease in isolation. Requires normal care.

34. Stable nuclear transformation. Plastids transformation. Transient transformation. Stable transformation .

35. ADVANTAGES Long – term non – refrigerated storage the seed upto 2yrs. Large acres can be utilized with the lowest cost. E.g – Grains. DISADVANTAGES Manual labor required. Lower yield. Less effective genetic. Outcrossing. Most common. A species with a long generation cycle. Foreign genes are transfer via Agrobacterium tumifaciens or particle bombardment. Genes are taken up & incorporated In a stable manner.

36. ADVANTAGES No outcrossing . Protein - upto 70% on dry weight. Very high expression levels can be achieved. DISADVANTAGES Protein unstable. Extraction & purification at specific time. Edible vaccine is not feasible since tobacco is highly regulated. First described by Svab et al . (1990). Tobacco species only. No transgenic pollen is generated.

37. ADVANTAGES Infection process is rapid . Small amounts target protein is obtained in weeks. Efficient for custyom proteins needed in small amount. DISADVANTAGES Not needed for protein in large amount. No long term storage due to tissue damage. Scalability & expression levels. Depend on recombinant plant viruses to infect tobacco plants like TMV. Target protein is temporary express in the plant. Protein accumulate in the interstitial spaces. No stable transgenic plants are generated.

38. ADVANTAGES Plants are contained in green house. Reduced fears of environmental release. Easier purification. DISADVANTAGES Expensive to operate . Not suitable for large scale production. Transgenic plants are grown hydroponically. Hydroponics is a technology for growing plants in nutrient solutions (water & fertilizers ) for high density maximum crop yield , crop production where no suitable soil exist. Desired products are released as part of root fluid into a hydroponic medium.

39. ADVANTAGES OF BIOPHARMING - Biopharming is much safer than extracting protein from living or recently deceased organisms. lower costs and rapid scalability lower manufacturing facility costs fast turnaround/response times, high-yield production enhanced safety, with lower risk of contamination with animal and/or human pathogens the ability to produce novel and complex molecules Various plant species can be used for biopharmaceutical drug production, including tobacco, moss, algae, alfalfa, rice and carrot. Biopharming offers several advantages over the other conventional methods of proteins production at higher levels.  The recombinant proteins are isolated from the various production systems of transgenic animals including urine, blood, milk, egg, plasma etc.

40. DISADVANTAGES OF BIOPHARMING - Due to the high dispersal rate of plant seeds and pollen, biopharming crops containing pharmaceuticals have the possibility of contaminating food crops. There may also be risks to insects and animals that pollinate or naturally consume the plants with high chemical loads . Biopharming in animals also poses risks. First, many believe it is immoral to change an animal’s genes for our benefit. It could be potentially harmful to the animal and have functions that can not always be predetermined. There are also worried that genetically modified animals could escape into the wild and impact the natural environment and wild species. Lastly, some critics believe that biopharming, or any other manipulation of genes, is unnatural and unethical. Critics argue that many animals that could be used for biopharming, like pigs, are highly intelligent social creatures and should not be used to produce pharmaceuticals. Others believe that genetic modification could have detrimental effects that we can not yet understand or predict

41. INDUSTRIAL PRODUCTS IN MARKET AVIDIN BY SIGMA • transgenic corn • traditionally isolated from chicken egg whites • used in medical diagnostics( The use of avidin-biotin immunoassay enhances the sensitivity of the technique and facilitates the detection of antigens in low quantities.) GUS (B-GLYCURONIDASE) BY SIGMA • transgenic corn • traditionally isolated from bacterial sources (E.Coli) • used as visual marker in research labs TRYPSIN BY SIGMA • transgenic corn • traditionally isolated from bovine pancreas • variety of applications, including biopharmaceutical processing • first large scale transgenic plant product • Worldwide market = US$280 million in 2014 (Promo pharma

42. COMPANIES

43. RISKS Contamination of food chain : If a food crop is used, the biopharma crop may inter-breed through pollen drift with the non-GM food crop and “contaminate” the food chain. This is a greater risk with outbreeding/ cross pollinated crops like maize. Food crops could also become mixed or mingled with bio-pharm crops through improper labelling, or mixing of seed in planting, harvesting, transportation, processing or through “volunteer” plants (i.e. remnants of previous harvests) not being eliminated . Both these routes are a cause for concern due to the potential harm to human health by contamination of food chain. Allergenicity : Plants process proteins differently from animals or humans - Thus, some experts are concerned that a plant-produced “human” protein could be perceived as foreign by the body and elicit an allergic reaction, including life-threatening anaphylactic shock. Impact upon non-target organisms : this is a known concern related to GM crops, but is a more significant risk for biopharming since the introduced gene or its product may have negative effects on the natural environment. For example, wildlife feeding on the crop may ingest harmful levels of the PBP, or soil micro-organisms may be inhibited by decomposing crop residue or substances exuded from roots of PBP plants. • Exposure: Farm workers may be exposed to unhealthy levels of a biopharmaceutical by absorbing products from leaves through their skin, inhaling pollen, or breathing in dust at harvest. Inconsistent dosage : Variations between the levels of proteins and other products expressed mean that the dosage has to be quality controlled and administration supervised. Unexpected effects on drug : Unexpected toxins or residues of pesticides used on the crop may contaminate the final drug product . The production of pharmaceuticals in the milk of transgenic farm animals has raised some biosafety concerns b ecause the expression of a transgene can be unpredictable, there is the risk that the protein product could “leak” from the mammary gland and enter the animal’s blood circulation to cause harmful systemic effects. Meat contaminated with potentially harmful pharmaceuticals might enter the human food supply. Transgenic farm animals may also have harmful environmental effects if they escape or are released from captivity and mate with wild individuals of the same species.  Two incidents involving the same company, ProdiGene , in the US have shown these concerns to be a reality. In 2001, ProdiGene failed to eliminate volunteer biopharm plants from a soybean crop planted later in the same field (Fox, 2003). The company was fined by the US Department of Agriculture (USDA) and was required to reimburse the government for expenses related to the destruction of the potentially contaminated soybean harvest (Byrne, 2008). ProdiGene was involved in a similar event in 2004 where volunteer transgenic maize contaminated an oat crop which was harvested and baled for use as onfarm animal feed, and was also found growing and flowering in a nearby sorghum field (Rybicki, 2009c). As a result of these two incidents, there is an effective moratorium on vaccine pharming in edible crops worldwide.

44. SOLUTIONS TO RISKS 1. The risk of cross-pollination is dealt with by isolation zones, managed cooperatively at industry level by searching for, and destroying rogues, i.e. plants that have escaped into the wild. 2. Volunteers are dealt with by crop rotations, spray regimes, tillage techniques, and by rogueing, or manually weeding crops. 3. Machinery is cleaned thoroughly to avoid the mixing of seed, and cleaning is monitored by production companies to make sure protocols are being followed. Furthermore, for very high value seed production companies use specially designated machinery. 4. Post-harvest there are sophisticated traceability and testing procedures to reduce the possibility of contamination. 5. These practices and procedures are highly effective and allow growers and production companies to consistently produce uncontaminated crops. 6. It is this experience of success that underlies grower and production company willingness to consider growing bio-pharm crops and their confidence in their ability to grow such crops with as great a degree of safety as is possible

45. ETHICAL ISSUES Concerns about escape of transgene. Should patents be allowed on transgenic animals? Limits data and animal sharing. Risk of escape of transgene viral vector. Welfare of other life forms. Ecological concerns. The use of farm animals for the production of human pharmaceuticals raises difficult animal welfare issues.  Does the benefit of biopharming to humans justify the use of animals for this purpose? For example, animal-welfare advocates, such as the British group Uncaged , have raised strong ethical objections to the use of pigs for xenotransplantation . They note that pigs are highly intelligent and social animals, and that efforts to eliminate PERVs would require raising them in isolated, sterile environments that would cause the animals emotional and psychological suffering and would result in abnormal behavioral development.

46. WHY PLANTS OVER ANIMAL BIOPHARMING?

47. REASEARCH AND PROJECTS Genetically engineered Arabidopsis plants can sequester arsenic from the soil. (Dhankher et al. 2002 Nature Biotechnology ) Immunogenicity in human of an edible vaccine for hepatitis B (Thanavala et al., 2005. PNAS ) Expression of single-chain antibodies in transgenic plants. (Galeffi et al., 2005 Vaccine ) Plant based HIV-1 vaccine candidate: Tat protein produced in spinach. (Karasev et al. 2005 Vaccine) Plant-derived vaccines against diarrheal diseases. (Tacket. 2005 Vaccine ) The current situation in the biopharming industry is difficult to assess. It is a developing industry with a large number of companies entering and exiting. Biopharming is one area of a larger industry focused on producing biological compounds of pharmaceutical interest. In biopharming, these compounds are produced using crop plants or livestock. The two largest research groups focusing on the production of human and animal vaccines and therapeutic proteins using plants are situated at the Council for Scientific and Industrial Research (CSIR) and the University of Cape Town (UCT). For example, the CSIR has produced RabiVir – a plant-made antibody cocktail for rabies prophylaxis – and plant-made subunit animal vaccines. The UCT has shown the first proof of efficacy of a plant-produced papillomavirus vaccine for humans and is also involved in various plant-made subunit animal vaccines. Further, AzarGen Biotechnologies is a South African SME involved in therapeutic protein production in plants, with their leading candidate recombinant product being a human surfactant protein that increases the survivability of premature infants. AzarGen has partnered with iBio , a US commercial bio-manufacturer for plant-expressed protein production. However, if the South African biopharming industry continues with the momentum that it currently has, local biopharming manufacturing facilities are also likely to be established.

48. FUTURE PROSPECTS Science has developed genetically enhanced crops and has/can develop plant-made industrial and pharmaceuticals crops. The extent to which these crops will be further developed for commercial and/or humanitarian use will ultimately depend on….. Scientists already proved the successful multiplication of many pharmaceutical compounds and vaccines apart from beneficial proteins antibodies etc. within plant system successfully with low cost. The biggest ever challenge solved was multiplication of Ebola virus drug ZMapp (Kentucky Bioprocessing LLC) in transgenic tobacco plants. Now India patented the drug to cure Zica virus (February 2016, Bharat Biotech company, Hyderabad). So it is a big challenge for India to multiply it within a short time to prevent the virus quickly spreading in the western countries, which can be achieved through biopharming. The only task before us is the non-acceptance of transgenics by government as well as the society. Hope if biopharming is accepted there will be tremendous improvement in target substance multiplication in a better and safer way. Public perception of risk Regulation

49. SUMMARY At present, environmental degradation and the consistently growing population are two main problems on the planet earth. Fulfilling the needs of this growing population is quite difficult from the limited arable land available on the globe. Although there are legal, social and political barriers to the utilization of biotechnology, advances in this field have substantially improved agriculture and human life to a great extent. Biopharming involves genetically engineering plants and animals, typically with human gene constructs, to produce biopharmaceuticals. It has thus far received little attention within bioethics or among social scientists. The nature and scope of the potential opportunities represented by biopharming remain unclear. The potential hazards associated with biopharming are wide-ranging and vary according to the “platform” used. Regulation of biopharming has not kept up with technological development and is arguably under-specified. Biopharming raises ethical issues in relation to the performative effects of inflated benefit claims, the infliction of harm and potential harm on bio-pharm animals and other organisms (including humans), the opportunity to consider alternatives and the significance and distribution of cost savings when evaluating biopharming’s acceptability, the values embedded in regulatory frameworks, and the proper response to uncertainty regarding far-reaching effects.

50. THANK YOU