BANGLADESH MAKES A BEGINNING!

On 30^th December 2013, Bangladesh approved the official release of four genetically modified varieties of insect-resistant Bt Brinjal for initial commercialization. Subsequently, on January 22, 2014, the seedlings of four Bt Brinjal varieties designated as Bt Brijal-1, Bt Brijal-2, Bt Brijal-3 and Bt Brijal-4 were distributed by Ms. Motia Chowdhury, Honorable Minister of Agriculture, Bangladesh to twenty small brinjal farmers of Bangladesh to undertake production of Bt Brinjal in a total area of two hectares to start with. Interestingly, the Government of Bangladesh was piloting the propagation of Bt Brinjal.

The authorization for limited commercial cultivation was subjected to stringent conditions to preparation of fields, maintenance of isolation distance, management of border row by planting local and indigenous non-Bt varieties, planting of a structure refuge of 5% with non-Bt varieties around the Bt Brinjal plot, marketing of Bt Brinjal as per seed leveling etc. The commercial plantation sites would be under surveillance of National Committee on Biosafety (NCB) and Biosafety Core Committee (BCC) of Bangladesh.

Earlier, the Bt Brinjal varieties were developed by the Bangladesh Agricultural Research Institute (BARI) of the Ministry of Agriculture, Govt. of Bangladesh. The release of the Bt Brijal varieties by the Honorable Minister succeeds the recommendation and approval of the four varieties by the Bangladesh Agricultural Council (BARC), Ministry of Agriculture (MOA) of Bangladesh and the National Committee on Biosafety (NCB) of the Ministry of Environment of Bangladesh. The four Bt varieties developed by BARI was through back-crossing of non-Bt varieties locally known as Uttara, Kajla, Nayantara and Ishurdi/ISD006 respectively with Bt Brinjal Elite Event (EE1) obtained from the Indian seed company Maharashtra Hybrid Seeds Co. Ltd. (MAHYCO), Jalna (INDIA) through the US Cornell University-led Biotech Support Project II. BARI infiltrated the Bt genes of event EE-1 into locally adopted and commercially popular brinjals of Bangladesh through repeated back-crossing. The varieties chosen were Uttara, Kajla, Nayantara and Ishurdi/ISD006 as mentioned above.

MAHYCO donated the EE1 to BARI in 2005 in a public-private partnership arrangement. The Bt Brinjal EE1 contains Cry1Ac gene and expresses insecticidal protein cry1Ac in whole plant and fruit parts. This protein is toxic to fruit and shoot borers (FBS). In Brinjal cultivation, particularly the FBS Leucinodes orbonalis creates considerable loss to the plant and to the fruits, rendering the latter unsuitable for marketing. The Bt Brinjal developed by BARI effectively prevents attack from FBS Leucinodes orbonali.

Between the period from 2005 to 2013, extensive experimentation was carried out by the authorities of Bangladesh. From such studies, it was concluded that Bt Brinjal could elevate the yields by above 30% over the non-Bt Brinjals and would reduce the spray of insecticides by 70-90%. These benefits would result in substantial net economic gain to the growers.

After the seedlings of the Bt Brinjal varieties were distributed by the Minister of Agriculture of Bangladesh in January 2014, the produce has started to enter the Bangladesh market. Several of the twenty farmers who received the Bt seedlings have shown great satisfaction as they have started to gain economically. It has been calculated that the economic benefit could be as high as over US$ 1800 per hectare where the annual per capita income in Bangladesh is only US$ 700; the gain is therefore substantial!

It is anticipated that the initial landmark decision of the Government of Bangladesh to distribute seedlings of four Bt Brinjal varieties would go a long way and over the years more of Bt Brinjal would be grown. This is more so because the varieties are open pollinated and farmers can save seeds for re-sowing in the next seasons. If the results of the commercial cultivation started in a small area of two hectares show substantial benefits, there is no reason why this would not create a great impact in uplifting the economy of the poor cultivators of Bangladesh. Brinjal is stated to be grown in Bangladesh in about 50,000 hectares of arable land by about 150,000 farmers of the country.

Of all the diseases of Brinjal, infestation from FBS is a major cause of loss. However, the plant is also affected by several other diseases like bacterial wilt and little leaf diseases. It is anticipated that the experiment of Bangladesh started in a small way will make room for doing more research to develop varieties that are resistant to other diseases of Brinjal too.

If the above story succeeds, we can guess that Bt varieties would also be introduced in rice, sugarcane, potato, maize and several other vegetables thereby making the availability of plenty of food from the arable land.

The Bangladesh experiment shall be an eye-opener for many other countries all over the world.

Source:   
http://www.isaaa.org; http://www.isaaa.org/kc; Choudhary B, Nasiruddin KM and Gaur K, 2014, The Status of Commercialized Bt Brinjal in Bangladesh, ISAAA Brief No. 47, ISAAA: Ithaca, NY;  
http://www.fao.org/publications/sofi/en/;   http://www.bhookh.com/hunger_facts.php

http://gandipsbio.com/Articles/Papers/12_GM%20Plants_Ind_Agri_1997.pdf

KEY AREAS TO BOOST MODERN BIOTECH SECTOR IN INDIA TO EMERGE AS A MAJOR GLOBAL PLAYER

The Indian Biotechnology sector is expected to emerge as a global key player as India has its strong pool of engineers and scientists, profound institutional network and cost-competitive manufacturing outfits. In addition the national research laboratories with their scientists can develop innovative R&D and application-oriented materials. The biotech industry turnover is considered to be over USD 5 billion in FY 2013-14 and is poised to grow at 15-18% per year.

BIOPHARMACEUTICAL SECTOR

Biopharmaceutical sector holds the major chunk of the biotech industry. While a wide range of products are manufactured, in the global context there is a great gap between what is available globally and what is available in Indian market in the following sub-sectors:

•        Humanized Monoclonal Antibodies of diverse kinds
•        Molecular Diagnostics and Point of Care devices
•        Vaccines especially to treat tropical and poverty-linked diseases, some viral and bacterial        infections
•         Vaccines to treat systemic disorders, e.g. prostate ailments, hormonal disorders, certain          cancers etc.

Humanized Monoclonal Antibodies

These products are entering into the market with rapid speed from different parts of the world. India is making progress but at a much slower pace. Biologics or Biopharmaceuticals or Similar Biologics or Biosimilars are terms coined by different countries for biological substances produced by living organisms. Such products are generally produced by recombinant DNA technology utilizing microorganisms or eukaryotic cell lines, depending upon the complexity of the biologics. The products are also purified by complex processes. Because of these inherent complexities, no two biologics produced by two organizations are exactly similar, although there exist substantial resemblance. Since the biologics are complex biopolymers, existence of all the molecules in specific orientation is also another issue as the bio-activities are linked with ligand-receptor interactions where the intact structures of molecules in right orientation are extremely important. Even though a large number of biologics is getting patent-expired every year and therefore, other manufacturers would try to encash the opportunity for business gain, worldwide there are debates among the regulators, the manufacturers, the users and the vocal public on issues relating to efficacy and safety of similar biologics supplied by other manufacturers who are not the inventors. The following issues in this context require to be addressed and resolved:

Ø  There is a strong contention from some countries that non-inventor suppliers of similar biologics should compare the efficacy of their products against one reference product only and that the reference product should be the product manufactured and marketed by the inventor. The issues among others are how to get the authentic bulk materials of the inventors; at best the formulated materials could be available from the market. Here also, issues of restricted availability or non-marketing of products in Indian market could create hindrance. The debate is therefore whether there could be exceptions to such assumptions and if so, what alternate solutions could be put forward that are doable and acceptable by the regulators in India and abroad.

Ø  There is good agreement among different stakeholders that the similar biologics should conform to the general physico-chemical properties of the inventors’ product. There is however disagreement about how much variation on the “residues” be allowed. There is also disagreement about how much purity, measured by which method is acceptable for a similar biological to be accepted as equivalent to the inventors’ product. There is a need to develop standards to resolve this issue for each biosimilar products and that such standards should be acceptable to the regulatory authorities all over the world. The debate is who is going to develop such a standard and wherefrom the basic inputs of information be obtained.

Ø  While a similar biologic can be produced by use of different recombinant hosts/cell lines, which are different from those utilized by the inventor, there can be disagreement about the product equivalence of the manufactured similar biologic as there could be minor difference in the content of impurities in such similar biologics from the inventor’s biologic. Here also an agreement is to be arrived at on the extent of the presence of the impurities and their safety as well as efficacy issues. The debate is, how could an unanimity be arrived at which is also acceptable to the regulators. 

Ø  While biosimilar products or similar biologics are supposed to be therapeutically interchangeable for different approved applications, there are issues and argument for agreeing to “interchangeability concept” based on different kinds of factors such as change in the cell line, change in the downstream processing operations etc. although the similar biologics may conform to the general physico-chemical properties of the invented biologic product. We need to come out with solutions that are acceptable to the regulators.

Ø  For generating efficacy and safety information on similar biologics, the trials that are required to be conducted following establishment of safety of the formulated similar biologics in approved animal models, the number of human subjects are to be limited and also the sites of trials are to be in smaller in numbers, as enough efficacy and safety information had already been generated by the inventors. The numbers of human subjects to be considered and also the testing sites are also a subject matter on which there is no unanimity as yet.

There is a need to prepare and announce a policy paper in consultation with the industry to promote the introduction of Similar Biologicals faster into the Indian market.

Molecular Diagnostics and Point of Care devices

India is yet much behind in the actual use of techniques of Diagnosis at molecular level as the nucleic acid extraction kits are expensive, not easily made in India and that the DNA amplifying machines are also expensive. This is also true for all other kinds of Point of Care devices. While there is an urgent need to set up target oriented R&D projects, efforts are also to be made to pinpoint which equipment, devices and consumables must be made locally to compete with the world. The industry can team up with the National R&D laboratories and draw a White Paper to cover these aspects.

Vaccines of diverse kinds

India has made strong contribution to the health of the people in the world by producing cheapest vaccines for containing childhood diseases commonly occurring from bacterial and viral infections such as DPT, Polio, MMR, Hepatitis B etc.

The world is making phenomenal progress in containing several disease conditions through immunological interventions, ligand-receptor interactions and signal modulation methods. Vaccines are making great progress in containing not only certain microbial diseases but also several kinds of cancer, auto-immune disorders etc. The emphasis in research and development in this country has also to keep pace with such advancements. Specific programs can be drawn up by the industry to suggest application oriented research in national institutes for doable product development in specific areas. India is yet quite behind in knowledge and applications in this important emerging area.

Certain systemic disorders leading to diseases related to post-industrialization syndrome such as diabetes, hypertension and stress among the working class including laborers are fast increasing. These are resulting in cardio-vascular diseases, stroke and kidney disorders. Different kinds of cancer are also rapidly increasing. Diagnosis, treatment and cure are the areas where new products can be developed and introduced by the industry. There is a need for encouragement and facilitation from the government in terms of policy support to promote diagnosis and therapy in these areas. There is a need to identify specific industry-related problems and prepare a white paper for a roadmap for future development.

Among the other areas in biopharmaceuticals requiring government and industry intervention are to treat cost effectively malnutrition, tuberculosis and certain viral diseases like HIV, HBV, HCV and HPV. Biotech inputs for the promotion of cost-effective products and services can be identified and specific government interventions for promoting such products in people-friendly programs can be thought about.

BIO-AGRICULTURE SEGMENT

GM seeds

In bio-agricultural sector including animal husbandry is another important area which needs promotion. Use of Bt-cotton technology in Indian agriculture made a sea change in increasing the production of better quality of cotton lint in the country and in promoting Indian textile industry in the global context. However, the GM technology for developing better seeds has been put to debate. This situation needs to be reversed. The industry should plead with the government to allow the development of GM seeds for a wide range of cereals, pulses, fruits and vegetables. The development in the Indian public sector institutions in GM research is inadequate compared to what such institutions have done in the development of quality hybrid seeds and varieties. Research needs to be intensified and extensive collaboration should be encouraged to develop GM technology in seed sector in the country. This is an area requiring extensive financial resources and the Indian government may like to take the lead. Industry can be active partners.

Bovine Somatotropin

Even though India produces largest quantities of milk in the world, the per-animal milk yield is yet very poor. Our dependence on buffalos for milk is very high and yet much needs to be done to improve the health of the animal. Moreover, the country also has a very large number of non-productive animals in all categories of mulching life forms. This situation can be tackled by using genetically modified bovine somatotropin to improve milk yield in mulching animals. The technology is doable and such products are already approved elsewhere in many countries. Milk yield can be substantially raised by use of bovine somatotropin.

GnRH

Increase in the fish production is constrained by several factors, one among them is the non-availability of adequate numbers of fingerlings. Different kinds of highly purified GnRH can be produced by recombinant DNA technology and these can be used to raise different kinds of fingerlings in proper seasons. Use of such fingerlings shall certainly contribute to increased production of fish.

BIOINDUSTRIAL SECTOR

Genetically Modified Enzymes

The consumption of enzymes in industry is rising at a galloping speed. In food, feed and fodder industry, a wide range of enzymes are being utilized. Proteases of various kinds, phytase, amylase, cellulose and lipase of a wide spectrum are being used for obtaining better quality of products. The dairy industry also is in need of various enzymes, especially for producing better quality of cheese. Rennet of different qualities is required for the industry. In detergent industry, the use of alkaline protease, lipases, amylases, cellulases and pectinases have also increased sizably. In leather, paper and textiles, the use of enzymes in various operations have also increased considerably. In order to meet the rising demand of enzymes, many countries have resorted to the use of genetically modified organisms for boosting production. In India the production is yet from non-recombinant organisms and therefore the yields are low. There is a need to relook at the whole operation and introduce genetically modified enzymes utilizing a wide range of GM organisms. This will not only boost the local industry but would also increase the availability of the enzymes considerably.

It is therefore suggested that the following factors and issues be considered in preference for preparing position papers by the country to promote the Indian Biotech sector during the coming years:

1.    All efforts should be made by the industry and the government jointly to ease the production of Similar Biologicals within the ambit of national and international laws.

2.   New and effective vaccines utilizing recombinant DNA technology should be promoted to develop newer therapies to treat a wide range of life-threatening conditions.

3.  Cheaper and cost-effective diagnostics based on nucleic acids need to be developed to diagnose and treat certain communicable diseases like tuberculosis, HIV, HBV, HCV and HPV. Besides, emphasis should be made to diagnose early systemic diseases such as diabetes, cardio-vascular ailments, diseases of kidney, arthritis and various types of cancer of different organs.

4.     Emphasis should be made promote the use of GM seeds in Indian agriculture.

5.   For increasing milk production, use of bovine somatotropin of various types need to be produced and utilized.

6.   For increasing fish production, the use of different kinds of purified GnRH should be intensified.

7.   Enzymes of various qualities required for the industry need to be produced by utilizing genetically modified organisms including E.coli, yeast and other microbial life forms.

8.    Industry and Government should work in close collaboration and utilize the public funded institutions to the maximum extent for generating new products and services in modern biotech sector. Where necessary, collaborations with knowledge intensive companies including the multinational corporations should also be promoted and intensified. Policy statements towards achieving such goals should be made on a faster mode.

NEED FOR EXTENSIVE USE OF GM SEEDS IN INDIAN AGRICULTURE

Indian agriculture is largely based on smallholder farmers; such farmers also make up for a large proportion of   undernourished people worldwide. But by the use of Bt-cotton technology in Indian agriculture, the economy has tended to bring about a change in the small holder farmers by contributing to an increase in their earnings (http://onlinelibrary.wiley.com/doi/10.1111/pbi.12155/pdf). India stood to become the second largest producer of cotton lint in the world by using the Bt- cotton technology, and is poised to become the largest producer of cotton in the world soon, beating China! Such is the contribution of this technology where small and medium holder farmers have also been immensely benefited. If cotton lint is available cheap in India, it would someday become the cheapest supplier of cotton garments to the world after it makes huge improvements in textiles and related technologies.

The latest report on “State of Food Insecurity in the World” mentions that about 842 million people (implying 1 in every 8 people in the world) suffered from chronic hunger in 2011-2013 (http://www.fao.org/publications/sofi/en/). One-third of such people live in India (http://www.bhookh.com/hunger_facts.php). The majority of these people live in the rural areas. The above figures are indicative of serious challenges to be met to increase production in agricultural sectors so as to enable increased income of rural poor. There is no doubt therefore that innovation in agricultural technologies requiring the use of new products and processes would play a key role in developing countries to face such challenges of food shortage.

Seeds are the most important contributors to agricultural productivities. The productivity of seeds is mainly contributed by the genetic makeup of plant cultivars/seeds (http://gandipsbio.com/Articles/Papers/12_GM%20Plants_Ind_Agri_1997.pdf). Use of modern biotechnology in agriculture to improve development of better seeds is certainly therefore one option in the hands of people to mitigate food shortage. The use of the tools of “modern biotechnology” provides insight for better understanding for the selection and multiplication of elite cultivars of varied types.

Use of plant tissue culture techniques for multiplication of clonal elites, followed by hardening of such elites in poly-houses and net houses has contributed to mass production of many plants of fruits and vegetables (http://nsdl.niscair.res.in/bitstream/123456789/668/1/revised+introduction+to+plant+biotechnology.pdf; India has been commercially using plant tissue culture techniques for the last two decades after activities and facilities set up for mass multiplication of elite plants by techniques of plant tissue culture were classified by the Indian Government as an industrial activity. Using tissue culture-raised elite plants, extensive increase in production of banana was possible. Banana cultivation is carried out majorly by the small and medium-scale farmers, utilizing purchased elite planting materials produced in tissue culture facilities. Banana occupies a distinct place in the national as well as in the household economy of Indians. Nutritionally, banana is rich in carbohydrates, vitamins and minerals. Cultivation of banana has provided a cash-income security to poor banana-growing farmers because it provides almost continuous income flow throughout the year, even under low input regimes (http://www.apcoab.org/uploads/files/1298295339pub_banana.pdf).

By use of "molecular marker-assisted” selection and combining this technique with “plant tissue culture” it is possible to identify, isolate and propagate stress-tolerant and highly productive cultivars. Using these techniques, several new hybrids have been invented such as pearl millet (hybrid HHB67) (http://www.icrisat.org/journal/bioinformatics/v2i1/v2i1teamwork.pdf) and rice (Swarna-Sub1 paddy seeds) (http://www.nature.com/srep/2013/131122/srep03315/full/srep03315.html), which have contributed to increased production, benefitting a large number of small  and medium land holders too, while making a considerable contribution to the economy of the country as a whole.

But there is more to it. By the application of genetically modified (GM) technology, combined with plant tissue culture techniques and molecular marker-assisted selection, the scope becomes enormously enhanced. The GM technology, according to Cartagena Protocol on Bio-safety (http://bch.cbd.int/protocol/publications/cartagena-protocol-en.pdf), is defined as the use of any “living modified organism” “that possesses a novel combination of genetic material obtained through the use of modern biotechnology”. By utilizing the GM technology, combined with the other two techniques, new GM plant cultivars and novel GM seeds can be developed. Using these new materials, the output in agriculture is expected to leapfrogging in progress as the integrated technology would provide benefits in several aspects to tackle pests and diseases while concomitantly enabling the usage of best cultivars for applications. Mother Nature has provided the varied genetic pool in her creativities. Intelligent recombination can be made by human to develop better combinations to benefit human kind. GM technology as is understood and developed at the present time worldwide provides opportunities for such new recombination although much requires to be understood about the technology. However, the technique as is in the hands of human kind can be used partly by precise knowledge and partly by empirically developed techniques to generate better seeds and more productive cultivars. The technique nevertheless provides great strength and opportunity to human for inventing new seeds and new plant development.

By utilizing GM technology combined with plant tissue culture and molecular marker assisted selection several countries have gone ahead to produce better seeds of cotton, corn, canola, soybean, papaya, potato etc. and that some 29 counties worldwide are being benefitted (http://www.isaaa.org/resources/publications/briefs/43/executivesummary/default.asp). In India, only Bt cotton technology is being commercially used and certainly more can be done.

Unfortunately, the use of this technology package is dominated by debate in many parts of the world especially in Europe even though the concerns have not yet been founded as actual in practice anywhere in the environment or to human and animal health. In India, by the use of Bt-cotton technology which is a GM technology, the country has enormously been benefitted in every respect including increase in total production, productivities and qualities of cotton lint as also in improving the economic benefits of the small and medium farmers. This was possible by the commitments and support of the Central and the State governments as also by partnerships/collaborations among national and international seed companies. There are also support from a wide section of the vocal public. But while the regulatory approval for the use of other inputs for supporting increased production of cotton such as the use of germ-plasms of elite cotton varieties and hybrids, fertilizers, electricity and water were already in place and the concerned Central and the State Ministries and their agencies were fully supportive to meet the needs of the Indian cultivators, the regulatory approval for the use of Bt-cotton technology was most crucial. After extensive evaluation, this approval was accorded by the Central Government in March 2002. Thus supports came about from all arms of the government and thereafter the results were magnanimous. Without an all-round support from all quarters, the results of Bt-cotton technology would not have been fructified in India.

It is believed that this is also true for being benefitted from the application of GM technology to tackle various stressful conditions in all other crops including cereals, pulses, vegetables, fruits and fibers. There is an urgent need to increase production and productivities in all such agricultural produce.

GM crops shall deliver products that are either cheaper or are nutritionally better or are more durable or can be grown is less friendly environment. GM crops can have multiple of such benefits.

But to a section of the vocal public, genetically modified crops technology is a controversy. This situation has to be changed by scientific reasoning, societal will and political desire if India wishes to address the food security and the broader economic issues of becoming more prosperous as a country.

The good news is that the National Committee on Bio-safety (NCB) in Bangladesh officially approved field release of four varieties of Bt-brinjal in October 2013 (http://cera-gmc.org/uploads/december_2013.pdf). Bangladesh became the first country in Asia to cultivate Bt-brinjal (egg plant), a product of a GM technology. The plants and their parts including the fruits of Bt-brinjal express Bt Cry1Ac protein and are therefore toxic to shoot borers, a destructive pest of the fruit. By cultivating Bt-brinjal, the yield of good qualities of eggplant is anticipated to substantially increase. It is expected that this announcement of Bangladesh will go a long way in enabling to adopt a whole range of GM technologies in many countries of the world and India would not remain an exception.

The Indian Public sector, which has contributed enormously to the developments in Indian agriculture, has contributed very little in GM–crops technology front. There is no dedicated Indian Public-Sector Institution for developing all aspects of GM–crops technology.

It is suggested that the new government, whoever may come, recognize the importance of GM technology and announce about setting up of a dedicated institution in the public sector, with a substantial outlay, to be spent over a period of years with detailed application-oriented programs to generate more basic understanding of GM-crop science and technology. The aim in one word should be to develop “better seeds” by application of modern biotechnology. Invention and innovations are the needs for the country in this very important area of agriculture.