Journal of Scientific & Industrial Research Vol. 60. ovcmbcr 200 I. pp 843-850

Biosafety: Problems and Prospects *

D Subrahmanyam ••

S Biotech. India

Advances in modern biotechnology arc being increasingly applied to product development for improved hcalthcarc. agricultural outputs and environment. The biotechnology industry has become a multi-bi lli on dollar industry. The extensive usc of recombinant DNA (rONA ) technology in industry, oft en entail s release of genetically modified organisms (GMOs) into the environment. There is a global concern that uncontrolled release of GMOs may bring about adverse effects on environment. and health of humans and animals. There is a strong support among nations that internationally binding biosafcty regulations arc needed for orderly application of biotechnology that ensures sa fety to health and env ironment. The nati onal and international initi atives towards th is goal have been ou tlined, discussed and the need for capacity strengt hening of developing countries. in this area. arc emphasized.

Introduction Traditional , biotechnology has been practiced for

millennia, in th e se lect ion of new plant va ri eti es, microorganisms and animals, for beneficial phenotypic characteristics and in production of fermented foods. Modern biotec hnology is essenti a ll y a c lu ster of tec hn olog ies enc ompassi ng ge nes, proteomics, recombin ant DNA (rONA), ce ll fusion and protein engineerin g. The advent of modern biotechnology, particularly in volving application of genetic engi neering, during the last over two decades , brought about an industrial revolution; it resulted in many high va lue added products that have great impact on health , agriculture and environment. Thus, biotechnology industry has become a multi -b illion dollar ventu re and a drivin g economic force. The enormous thrust made by th e industry using this technology brought in its wake concerns , regardin g safety to hea lth of humans and an imals, and to the environment. This paper dea ls with a brief rev iew of the advances occurring in this area; their actua l and presumed benefits; their potenti al impact on health , agriculture and envi ronment ; and the globa l approaches being devised to tack le the biosafety issues, including those under the United Nations system. The

·This paper is based, in pan, on a presentation at the Indian Science Congress. 2001 held at New Delhi, India in January 2001.

' 'Co rresponding author; address: A20. Swas thy a Villar. Delhi II 0 092, India; c_mail : subraml O@ hotmail.com.

problems and prospects of developing countries tn tackling biosafety issues are also outlined, and that may be the main purpose of the paper.

Applications of Biotechnology

(i) Healthcare

In the area of hea lthcare, application of modern biotechnology lead to sequencing of the human genome, and a better kn ow ledge of disease processes. The sequence databases, held in gene banks, together with advances in bioinformatics are li kely to change the face of biomedicine. Application of reco mbinan t gene technology facilitated (Table I ) rapid production of vi tal pharmaceutica ls 1

, diagnosti cs1, vaccines3 and opened up

new vistas in effectively tack ling genetic disord ers . Prod ucts such as humulin , e rythropoiet in , ti ssue plasminogen activator (TPA), human growth hormone, several mediators and clotting factors are already in the market (Tab le I ).

Table !-Impact of biotechnology on hcalthcarc

I Knowledge of di sease processes

2 Recombinant gene products

3 Diagnosti cs

4 Vaccmes 5 Gene therapy

X44 J SCI IND RES VOL 60 NOVEMBER 2001

Farm animals have also been used as bioreactors

to produce vital human medicines in large quantities. A new fie ld of pharmacogenomics has arise n, which

promises to y ield medicines tailored to specific altered

genes . Recombinant antigens, polymerase cha in reaction

(PCR) applications, DNA probes, and mon oc lonal

ant ibodies have revolutionized diagnostic tech no logy

(Table 2).

Vaccines are the first line of defe nse again s t

diseases, and currently, the available vacc ines prevent more than 3 million deaths an nua ll y among chi ldren.

Vaccination being the most cos t-effect ive, re lati vely

inexpensive and practical way of preventing infection ,

considerabl e progress has been made in this area by the app li ca tion of modern biotechnology. Advances in

geneti c engineering resulted in improvement of ex isting

vaccines, e limination of severa l vaccine-re lated untoward

reactions, development of s ingl e-dose delivery or

multiple protective epitopes, s low re lease formu lations, DNA vacc ines, and effic ient vectors for vaccine de li very.

More recent ly, plant-based edibl e vaccines are being

developed wh ich offe r great pro mise in combating infec tions, rang ing from bacterial to viral in o ri g in ~ 5

(Table 3).

Long strides are being made to bring gene therapy

researc h on a sound foot ing. This a rea is ex tre mely

promising in correcting genetic disorders, rang ing from haemophilia , diabetes to cancersli. Techniques have been

developed in producing stem cell s, in large amounts fo r

therapeutic purposes.

(ii) Agriculture

The phenomenal annual increase in population o f

over I 00 million warrants en hanced food production , at

leas t @ 2 pe r cent/y. India a nd China , with th e ir

respective populati on currently exceeding one billion,

need to double the food production, in the nex t ten years. Application of modern biotechnol ogy to agriculture has added a new dimension in our ability to meet the ever­

increas ing need for food , consequent to popul a ti on explos ion7 . This technology offers promise (Tabl e 4) to transform from a condition of food scarcity to food security. In thi s co ntex t, cash c rops with improved agronomic traits that are res istant to pests such as viruses , insects and fun g i have been developed and fie ld- testedx. 9 . Genomic sequences of important plants are being

estab lished, which would provide important insights into the way plants cope with pes ts and diseases. It , in turn ,

2

3 4

Table 2-Diagnostie~

DNA rrobes on gene chi rs

PCR

Recombinant anti gen~ Monoclona l antibodies

Table 3-Ncw and improYcd vacc ines

Increase in potency

2 Oral vacc ines

3 Elimination of pathogenic components

4 Polyvalent vaccines

5 New vectors for delivery

6 D A vaccines 7 Edible vaccines

Table 4--lrnpact or biotechnology on agricu lture and animal

husba ndry

Pest resistance

2 Salinity and drought resi~tance

3 Embryo transfer

4 Tissue culture

5 Agronomic traits

6 utritiona l enrichment

7 Hybrid seed

8 Industrial chemicals

9 Monoclonal ant ibodies I 0 Edible vaccines

would facilitate development of be tter d isease-resis tant

pl ants 111• It is s ignificant in thi s context to note the recen t

accompli shment of dec iphe rin g full seq uence of the geno me of Arabidopsis thaliana 11

• Pl ants, which a re

herbicide res istant and tolerant to abiotic stress, are be ing cultivated . Gene tica lly modified (GM ) crop p lants that y ie ld products w ith improved quality and nutriti ona l value, have been developed. A new green revoluti on is in the offing, in development and comme rcia li za ti on of staple produc ts such as vitamin A-rich rice, droug ht­res istant wheat and corn , and vegetables and fruits with

longer shelf life .

Bes ides industrialized countries, many deve loping

countri es a re producing tra nsgen ic c rops for commerciali zation. Argentina is the third largest producer

SUBRA II MA YAM: BIOSAFETY-PROBLEMS & PROSPECTS X-+5

of biotechnology-based crops in the world. after USA

and Canada, and is a lso engaged in their exports. China

is among the fi rst to grow, commerciall y, GM-cotton and tobacco, bes ides other cash crops. Indi a is ac ti ve ly

developing a variety of transgenic plants such as cotton,

o il seeds, vegetable plants, tobacco and rice.

(i ii) Environment

Modern biotechnology is also be ing used for

cleaner env ironmental applications 12• Biopesticides.

biofertilizers, biodegradable plastics and bioleaching are

replacing the respect ive conventional, but polluting

processes. The techno logy is being increasingly app lied

for waste d isposa l and management ; waste water

purification and bioremediation (Table 5).

Concerns

The advent of rON A technology pro v id ed unprecedented opportunities for hori zontal and vertica l

transfer of genetic e lements, w hich underscored se ri ous

concerns (Table 6) of safety to human and animal hea lth

and to the envi ronment in lay publi c. environmentali sts,

decisi o n makers, and in even among some lead in g sc ientists. Application of genetically mod ified organi sms

(GMOs) for industrial deve lopment, often enta ils re lease of GMOs into the environment for fie ld-test ing and for eventua l use. Severa l such re leases have a lready taken

place in not onl y the developed countries but also in

developing countri es of Asia and the Far East, and in

Latin America. Considerable g lobal concerns have been

expressed that such a re lease of GMOs may result in

manifested dele te ri ous effects, such as co lonization of

non-indigenous organi sms, di smption of ecosystems 13,

and inadvertent evoluti on of pathogenic tra its.

It is pertinent to record here a few examples of such actual and perce ived ri sks.

Potential exists for out-c ross ing to a wild re lative

spec ies, that might coex ist w ith the transgenic c rop, creating super weeds 14

• Mon santo decided not to

pursue th e developme nt of he rbi c ide- res istant sorghum tha t outcrosses with a weed (Johnson grass) to avoid such a dangerous poss ibility. In a recent stud y, Wilkinson from U. K. observed that he rbic ide res istance could spread from genetica ll y

modified oilseed rape to its wild re lati ves like wild turnip. A case of accidental , and uninte nd e d

2

3

Table 5-Environmental applications

Waste water purification

2 Waste disposal and management

] Biodegradab le plastics

4 Bioleaching 5 Bioremediation

Table 6-Conccrns

Outcrossing to wild relatives

2 Generation or new pathogens

] Allergenic nove l proteins

4 Damage to non-target organisms

5 Development or resi stance

6 Loss or genetic diversi ty

7 Errects on animal and human health 8 Socioeconomic and eth ical concerns

acquisition of herb ic ide resistance was a lso noted.

Sugarbeets geneti ca lly mod ifi ed to res ist herbicide. g lu focinate, were fo und to acquire resistance to anot her herbic ide, g lyphosate.

Vector-med iated horizontal gene tran sfer, or vector reco mbination , may gene rate new path ogenic

bacteria, or new virulent strai ns of virus. A gene for res istance to a he rbicide introduced into rapeseed

was found in bacteria iso lated from the gut o f bees

that ate po ll e n from th e rapeseed . Rece ntl y,

Au stra li an sc ienti sts accidenta ll y c reated a more virulent stra in 15o f mou sepox virus when it was

modified to inc lude a gene for inte rl eukin 4 {IL-4).

which was intended to stimul ate greate r immune

response. In stead , the modified virus, that normally does not kill the strain of mice used , became lethal to the animals.

Modified plants may contain nove l prote in s th at may provoke allerg ic reactions. Recently, Avent is, USA withdrew Taco she ll s from the market, as it was conta minated with a Bt-protein , Cry9C, a potential a ll e rgen. which was not appro ved for

human consumption. More recentl y, Aventis found Cry9C in yet another variety of mai ze, the ori gin of which is unde r inves ti ga ti on. A case of c ross­pollination may be invol ved in it. There is a g reat need for strict control for segregation of geneti ca ll y­modified (GM) plants , particularl y those inte nded

J sel I\'D RES VOL «o ",OVUvlllER 2()OI

for USl: as foods. to prevent cross-pollination orplants. Certain plants. like rapeseed and canula.could be used both for production of roods as wellas for industrial chemicals, like lubricants. Thoseused for food purposes should be cff'cctivc lyseparated from the ones intended Ior production ofchemicals. which arc toxic.

4 Extensive Lise of Bt-tox in containing: crops GIn havepotentially negative impact on ecological processesand the non-target org;l!1isms. Pollen from maize.engineered to make Bt-inscctiridc. could killmonarch butterflies, thus causing ecol o g ic alimbalance. Heavy herbicide applications in a fieldresults in severe reduction in weeds that eventuallyaffect the bird population that live on them.

Insect pests develop resistance to crops with Bt-toxins.

6 Widespread and continuous use of a singletransgenic monoculti var may lead to loss of genet icdiversity. Genetic homogeneity causes greatervulnerability in plants to biotic and abiotic stresses.

Arapad Pusztai, from Scotland, reported in 1008that genetically modified potatoes when fed to ratsresulted in immune defects in the animals.

7

8 Socio-economic and ethical concerns arc alsoexpressed by developing countries. Overproductionof biotechnology-based products and productsubstitution are affecting the traditional agriculturaland industrial exports. Several examples urcirnmcdiate ly obvious, viz.. (i ) production of thesweetener, thaurnntin, affecting the sugar markets:(ii ) cloning oil palms alTecting groundnut farmersof Senega I and coconut fanners of Ph i Iippincx; ( i ii)production of aromatic cultures in biorcacror-, beillgperceived as a threat to vanilla, coffee and cocoaindusuies etc. Inadequate expertise ill adoption andpractice of new technologies lead to increasedm.ug i n a l ixut io n of small farmers and Ltil inemployment in their counuies.

Risk-benefit Analysis

In view of the benefits and concerns cnurncmtcdabove, one must we igh carefully whether it is prudcnt roreject a technology that could deliver rc l.u ivc lyinexpensive vaccines and medicines and help wean IIlL'wo rld off fossil fuels. The key c o ntri hut ion s ofbiotechnology, and risks of not availing its benefits, such

ax loss of rain forests. low food output and consequenthunger and malnutrition in ever expanding populations,inadequate new ton is tll fight diseases and environmentaldcgradat ion must be addressed before tak ing any stepsto limit its use. It should be realized that there is nothinglike zero risk in any new technology. However. thereseems to be a need for a careful analysis of risks. both

hypothetical and real. in till' application of biotechnologyfor industrial and economic dcvelopmcnt". One shoulddetermine acceptable rixk lc vc!s. in relation to thebenefits obtained from the application of a technology.Risk analysis should he clone step-by-step and Glsl'-hy-case, and it should be based on sound xc ic nt i licprinciples, and on the quality of the product rather th;1I1the process adopted.

Risk analysis comprises both risk assessment andrisk management. Risk assessment in the introductionof GMO should be carried out by identifying ha/ards,based on characteristics ofthe organism, familiarity. theintroduced trait, the environment in which introduced,its interaction with the environment. and the intendedapplication. Once, a hazard is predicted on introduction,other aspects such as, its magnitude. its likelihood ofoccurrence, quantitation of the risk, if possible, andevaluation of the risk, in terms of cost/benefit analysisshould be considered. Further considerations involvedin risk assessment arc (i) the stabi I it y of inserted gene inthe GMO, (ii) its impact on non-target species, (iii) itsadverse effect on health and the ecosystems, (i \.) itspotential for weediness, (v) its phenotypic expression(such as cornpcriti vcncsx, pathogen ic iIy and vi I'll lcncc).and (vi) its possibilities 01' inducing genL'lic altcrutionx.

Risk management must a dd re s s t h c Illoslappropriate measures 10 minimize identified risks :111r1methods to mitigate clfcctx ofri sk s. Potential risb mus:he compared with the bcnc l'itx. including cconomi«conxidcrntion«. before decisions arl' taken on thl' USl' ofGI'vIOs.

1\ational Initiati vex on Biosufctv

Countricx or \"llnh Arncrica and till' FurOpC;\I1Union have promulg.ucd hillsakty guidl'linl~s with riskperceptions, r;\I1ging lrom minimal t() high lcvcl-; inappl ic.u ion of CiM()s for indust rial development W hi lcthe govcmment and industry in the US Iccl. PII1dllctsmack through genetic enginl'l'rJng arc pructic.ill , IHldifferent Irorn similar ones mack by conventional

SUBRAHMANYAM: BIOSAFETY-PROBLEMS & PROSPECTS

methods, those in European Union and Switzerland areagainst the introduction of GM-crops. Currently, France,Italy, Germany, Denmark and Luxembourg preventintroduction of all new GM-products in the Europeanunion. In a recent survey, conducted in Europe, it wasfound that public perception on modern biotechnologywas generally opposed to GM-foods but was morefavourable towards medical and environmentalapplications ". Many of Europe's supermarkets andrestaurants display themselves as GM-frec. AxisGenetics of United Kingdom could not proceed withclinical trials of vaccines, developed in foods (ediblevaccines), against diseases such as hepatitis and choleradue to reluctance of venture capitalists to fund thedevelopment of such GM-foods. Support forbiotechnology is also declining in Japan".

Many countries of Asia and the Far East areapprehensive in the commercialization of GM-crops.Among these is Sri Lanka, which banned GM foods,pending further research. Brazil prohibited importationof GM-foods unless safety is documented. Even China,with its liberal attitudes towards GM-crops, requireslabeling of GM-seeds.

Several developing countries notably, Argentina,Brazil, Costa Rica and Mexico from Latin America;Egypt, South Africa, and Zimbabwe from Africa; China,India, Malaysia, Philippines and Thailand from Asia havedeveloped sound biosafety guidelines. In India, theMinistries of Environment and Forests, and Science andTechnology, oversee the biosafety matters with effectiveand comprehensive guidelines which were further revisedin 1998. The Genetic Engineering Approval Committee(GEAC) and the Review Committee on GeneticManipulation (RCGM) monitor adherence to thestatutory provisions laid down for research andapplication of GMOs. Extensive biosafety informationis sought from the proposer of field trials of GMOs inorder to assess risks involved, if any, and to ensure safetyto health and environment, before the trials are approvedby the government agencies. The biosafety guidelinesand their effectiveness have been elegantly reviewed justrecently".

International Initiatives on Biosafety

United Nations Industrial DevelopmentOrganization (UNIDO) at Vienna is one of the earliestinternational agencies, which realized the potential of

~47

modern biotechnology, and the benefits that could hederived on its application for industrial development.Having been actively involved since the early 70s, infostering biotechnology in developing countries, UNlDOrealized the need for orderly application of biotechnologythat ensures safety to health and environment. To thisend, UNIDO set itself certain objectives to promoteinternationally acceptable biosafcty policy andguidelines, and training and technical support to itsmember countries. UNIDO established an inter-agencyWorking Group on Biosafety (WGB) in 1983, incollaboration with the United Nations EnvironmentProgramme (UNEP) and the World Health Organization(WHO) to which Food and Agricultural Organizationlater joined as a member. Other organizations have comeup with biosafety guidelines. The Organization ofEconomic Cooperation and Development (OECD)published a document in 1986 on Recombinant DNASafety Considerations. The European Commission (EC)released its directives in 1990 on the contained use anddeliberate release into the environment of GMOs.

One of the aims of the WGB, of UNIDO/UNEP/WHOIFAO, was to promote environmental applicationsof GMOs for industrial development, in a safe andecologically sustainable manner. To this end, WGB tookseveral initiatives, vir, (i) release of a manual on aninternational approach to biotechnology safety, (ii)develop a Voluntary Code of Conduct (VCC) for releaseof GMOs, and its annotated version": (iii) organizeannual training programmes on biosafety; (iv) publish abiosafety guidebook on the release of GMOs; (v) help insetting up institutional (IBC) and national biosafetycommittees (NBC) in member countries; and (vi)establish Biosafety Information Network and AdvisoryServices (BINAS).

The VCC outlined responsibilities of researchers,national authorities, and industry, for safe application ofGMOs, and aimed at harmonization of biosafetyguidelines. BINAS provide information support withdatabases on regulations and guidelines adopted indifferent countries, on national authorities responsiblefor taking decisions for use of GMOS, list of expertpanels in risk assessment and management, field releases-taking place around the wor1cl-and their environmentalimpact. BINAS also provide advice to IBCs, NBCs andindustry, to facilitate safe application of GMOs andfacilitate consumer confidence in and acceptance ofproducts such technologies.

848 J SCIIND RES VOL 60 NOVEMBER 2001

Arising from these initiatives, in an expanded andimproved form, were the Anglo-Dutch proposals tosupport the development of voluntary guidelines forsafety in biotechnology. These guidelines were aimed toassist governments, to develop their own biosafetymechanisms, in line with international cooperation andharmonization.

Agenda 21

The need for an international framework onbiosafety was given due importance at the UnitedConference for Environment and Development"(UNCED) in 1992. The Agenda 21 of the UNCED,specifically endorsed the requirement forenvironmentally sound management of biotechnology.Chapter 16 of the Agenda 21 stated that there was needfor development of internationally agreed principles onrisk assessment and management of all aspects ofbiotechnology. Agenda 21 emphasized that whenadequate and transparent safety procedures are in place,the public would be able to analyze the potential benefitsand risks of biotechnology and derive maximum benefitsfrom the technology.

Convention on Biological Diversity

Parallel initiatives on biosafety were taken byUNEP's Convention on Biological Diversity" (CBD).The CBD, developed and ratified under the auspices ofUNEP, was intended to promote conservation ofbiological diversity, sustainable use of its components,and fair and equitable sharing of benefits, arising onutilization of these resources using relevant technologiesincluding biotechnology. CBD contained provisions foravoiding or minimizing possible risks from GMOs.Recognizing the potential for risks associated withbiotechnology applications, the CBD outlined, underarticles 8g, 19.3 and 19.4, steps to be taken by membercountries in matters relating to biosafety. These are toestablish or maintain means to regulate, manage, orcontrol the risks associated with the use, and release ofliving modified organisms (LMOs), which are likely tohave adverse impact on health and environment. TheCBD also suggested the need for a biosafety protocol,the modalities of which could include appropriateprocedures, such as, advanced information agreementin safe transfer, handling and use of LMOs.

Cartagena Protocol on Biosafety

Accordingly, an internationally binding safetystandards protocol, entitled Carte gena Protocol onBiosafety (CPB) was adopted" by the CBD in early 2000.The CPB has been proposed to regulate thetransboundary movement of specific categories of LMOs.LMOs intended for direct use as food, feed or forprocessing (LMO-FFP) are subjected to thePrecautionary Principle (PP), which allows action to betaken, if there is a suspicion of any potentialenvironmental damage, even without having fullscientific proof. Thus, PP shifts the burden of provingthe safety onto those who wish to release the GMOs.CPB enables setting up minimum standards for riskassessment and safety measures for the transboundarymovement of GMOs. As per the CPB, the party thatexports the GMO under the Advanced InformationAgreement (AlA) has to notify the importing party withinformation on the GMO, such as identification methods,centers of origin, or the risk assessment reports. Theimporting party has the right to decide on the importafter assessing the reports received on the GMO. Further,the LMO-FFP must be labeled appropriately, includingthat these are not intended for release into theenvironment. CPB also proposed development of aninternet-based Biosafety Clearing House (BCH), aninformation system on the GMOs and their movementthrough international trade. CPB further calls forresources, from member countries, for technicalassistance and capacity building in adoption ofbiosafetymeasures. It is pertinent to note that USA, one of threelargest countries producing and exporting GMOs is nota signatory to the CPB as the country has not yet ratifiedtheCBD.

Conclusions

The prospects for adoption of ecologicallysustainable biosafety measures, which are also safe tohealth and environment, seem bright. USA has long feltthat GMOs do not generally pose untoward, andinsurmountable safety problems because rDNAtechnology used in producing them is merely anextension of the traditional methods of geneticmodification with better precision. However, USA isreviewing its stand and questions on biosafety areconsidered legitimate. Although a majority of Citizensof USA remains supportive of modem biotechnology,the extent of opposition to it is on the rise". A proposal

SUBRAHMANYAM: BIOSAFETY-PROBLEMS & PROSPECfS 849

to enact Genetically Engineered Food and Safety Act(GEFSA), which subjects all transgenic components ofbioengineered foods to premarket review as foodadditives, is gaining momentum. FDA of USA also statesthat if bioengineering produces a material difference inthe product, it should be labeled. USA and EuropeanUnion recently established a Biotechnology ConsultativeForum (BSF). A committee constituted by the BCFrecommended a tighter control on GM-foods includingmandatory labeling and government approvals on safety.UK and Europe and Japan are proceeding cautiously inapproval of genetically engineered foods and adoptprecautionary principles with regard to GMOs. Anextensive debate on the safety of genetically modifiedfoods has recently been published". In the UK, anAdvisory Committee on Releases to the Environment(ACRE) submitted a report on how to minimize risks ofgene flow and reduce risks to biodiversity. Mostdeveloping countries are apprehensive on the release ofGMOs although many of them including China, Indiaand Thailand and few Latin American countries areactively testing them in the field. These countries arealso investing in establishing research facilities that canproduce GMOs within their countries. The developingcountries are now more confident on biosafety with theadoption of CPB.

Problems in ensuring biosafety continue to remainat large. CPB does not cover other LMOs, such as thoseused as pharmaceuticals. Biosafety evaluation stilldepends on the legal framework of individual countries.Many developing and least developing countries do notstill have national biosafety legislation or biosafetyguidelines, and necessary expertise and resources fordecision-making on proposals for the introduction ofGMOs for industrial development. The protocol also doesnot address liability and compensation issues arising outof any damage caused to the environment and healthrelating to handling, transport and use of GMOs. Theinternational organizations, NGOs and industrializedcountries should consider providing resources andsupport in capacity building in these countries and instillconfidence in them in using the frontier technologies insafe and ecologically sustainable manner for theeconomic development.

Notwithstanding the above, with national, regionaland international organizations working in tandemtowards harmonization of biosafety guidelines andbuilding expertise in risk 'assessment and management,

prospects for safe use of modem biotechnology forindustrial and economic development worldwide,appears promising.

ReferencesHodgson J, Business and regulatory news, Nature Biotech, 14(1996) 560.

2 Green E, Metabolic and molecular basis of inherited disease, inThe human genome project and its impact on the study of humandisease edited by C R Scriver, 81h ed (McGraw-Hill) 2000.

3 World vaccines and immunization (WHO/UNICEF Publication,Geneva) 1996.

4 Mason H S & Arntzen C J, Transgenic plants as vaccineproduction systems, Trends Biotech, 3 (1995) 388.

5 Richter L J, Thanavala Y, Arntzen C J &Mason H S, Productionof hepatitis B surface antigen in transgenic plants for oralimmunization, Nature Biotech, 18 (2001) 1167-1171.

6 Verma N & Somia N, Gene therapy - promises, problems andprospects, Nature, 389 (1997) 239-242.

7 BorJaug N, in Meeting the challenges of population, environmentand resources: The costs of inaction (World Bank Publication)1996.

8 Tu J, Zhang G, Datta K, Xu C, He Y, Zhang Q, Khush G S &Datta S K, Field performance of transgenic elite commercialhybrid rice expressing Bacillus thuringiensis delta toxin, NatureBiotech, 18 (200 I) 110I-II 04.

9 Moellenbeck D J, Peters M L, Bing J W, Rouse J, Higgins S,Sims Y, Nevshemal T, Li et al.lnsecticidal proteins from Bacillusthuringiensis protect corn from corn rootworms, Nature Biotech,19 (2001) 668-672.

10 Stuiver M H & Custers J H H V, Engineering disease resistancein plants, Nature, 411 (2001) 865-868.

II The Arabidopsis Genome Initiative, Analysis of the genomesequence of the flowering plant Arabidopsis thaliana, Nature,408 (2000) 796-815.

12 Loveley D R & Lloyd J R, Microbes with a mettle forbioremediation, Nature Biotech, 18 (2000) 600-601.

13 Wolfenbarger L L & Phifer P R, The ecological risks and benefitsof genetically engineered plants, Science, 290 (2000) 2088-2093.

14 Mikkelsen T R, Andersen B & Jorgensen R B, The risk of croptransgene spread, Nature, 380 (1996) 31-32.

15 Jackson R J, Ramsay A J, Christensen C D. Beaton S, Hall D F& Ramshaw I A. Expression of mouse interleukin-4 by arecombinant ectomelia virus suppresses cytolytic lymphocyteresponses, J Virology. 75 (2001) 1205-1210.

16 Levin M A & Straus H S, Risk assessment ill genetic engineering(McGraw Hill) 1991.

17 Gaskell G, Allum N, Bauer M, Durant J, Allonsdottir A.Bonfadelli H et aI, Biotechnology and the European public.Nature Biotech. 18 (2000) 935-938.

850 J SCIIND .RES VOL 60 NOVEMBER 2001

I 8 Macer D & Ng M A C, Changing attitudes to biotechnology in Japan, Nature Biotech , 18 (2000) 945-948.

19 Ghosh P K & Ramanaiah T V, Indi an rules, regulati ons and procedures for handling transgenic plants, J Sci lnd Res. 59 (2000) 114-1 20.

20 Subrahmanyam D, Annotated voluntarv code of conduct ./(n release of genetically modified 0/~fian isms (U ni ted Nations Industrial Development Organi za tion Publicat ion) 1992.

21 Proceedings of United Nations conference 011 environment and development, Res Rep No. 55 (U CEO, Unit ed Nations Publication) 1992.

Abbreviations Used

rONA, recombinant DNA GMOs, geneti cally modified organi sms LMOs. living modified organ isms TPA, ti ssue plasminogen acti va tor PCR, po lymerase chain reaction GM, genetically modified Bt , Bacilltu thuri11giensis GEAC, Genetic Engi neering Approval Committee RCGM , Review Committee on geneti c manipulati on Ul\100, United Nations Industrial Development Organization UI\EP, United Nations Environment Programme WHO, World Health Organizatio n FAO, Food and Agriculture Organi zation

22 Convention on biological diversity (Uni ted ations Environment Programme Publication, UNEP) 1992.

23 (i) The editors, Working towards a strong protocol, Biotecluwl Dev Mon, No. 43. (2000) 2-3, and (ii ) Meyer H, The Cartagena protocol on biosafety. Biotechnol Develop Mon. No. 43 (2000) 2-7, www.hiotcch-mnnitnr.nl

24 Pri est S H, US public opini on divided over biotechnology. Nature Biotech, 18 (2000) 938-942.

25 Genetically modified foods: Are they safe~ (a series of artic les).

Sci Am, 284 (4) (200 I) 50-65. www.sc i :.~m.com

OECD, Organi zation of Economic Cooperation and Development NBC, National Biosafety Committee IBC, Instituti onal Biosafcty Committee BIN AS. Biosafcty Informat ion Network and Advisory Service VCC, Voluntary Code of Conduct WGB , Working Group on Biosafety UNCED, United Nations Conference on Environment and Development CBD, Conventi on on Biodiversity CPB , Cartegcna Protocol on Biosafety AlA , Advanced In formati on Agreement FFP, Food, Feed or for Processing BCH, Biosafety Clearing House GEFSA . Geneticall y Engineered Food and Safety Act BCF. Biotechnology Consu lt ative Forum FDA, Food and Drug Adminis tration