DEVELOPMENTS IN BIOTECHNOLOGY: PROGRESS, PROBLEMS AND PROSPECTS

: The clevelopment of Biotechnology in Lanlta is reviewed in the context ol similar developments elsewl~ere, with special reference to India, Brazil ancl developccl countries. Support for Biotechnology from overseas research funding agencies and the Natural Resources, Energy ilnd Science Authority (NARESA) the National Science Founrlation (NSF) 1 is outlined.


INTRODUCTION
Biotechnology in its broadest sense is the use of other organisms for producing the needs of human beings. In such a context, biotechnology is as old as human civilisation'. For example, wild grass varieties were selected and grown as wheat in the Middle East in 9000 BC, and as rice in South and East Asia in 4500 BC. Cotton was cultivated in the I~ldus val.ley by 3000 BC. Alcohol.ic beverages have been pr-oduced by ftrrnentation since recorded history. Recent advances in cellular and molecular biology have however dramatically enhanced our ability to manipulate cells, micr-oorganisms and indeed human beings and otl~er mammals. Some landmark discoveries made in this century include the demonstration in 1941 by Beadle & Tatum that a single gene codes for a single protein, Avery's proof in 1944 that DNA is the genetic material, elucidation of DNA structure in 1953 by Watson & Crick, the discoveries of restriction enzymes, DNA polymerase, reverse transcriptase etc., that permitted gene cloning, the productjon of' monoclonal antibodies in 1975 by Kohler & Milstein and more recetltly the discovery of the polymerase chain reaction to amplify specific regions of DNA molecules. Considering the recent scientific discoveries and technological advances, the European Federation of Biotechnology in 1981 adopl;ed a useful working definition of biotechnology as "the i~ztegrated use of biochenzist7-y, micl-obiology cirtd clremical engilleerilzg to achieve tlzc tecl1,17.ological! applications of the capacities of microbes and c z~l t~~r e d cells ".

DEVELOPMENTS IN BIOTECHNOLOGY IN OTHER COUNTRIES
The impact of biotechnology on the economy, health, agriculture, industi-ial production and the environment was recognised very early in Japan and countries in North America and Europe. This was due to their advanced industrial 1 economic forecasting and planning capabiIitics. A few other countries, notably Argentina, Australia, B1-azil, India, and Thailand were also able to grasp, a t a relatively early stage, tbe possibilities inherent in biotcchnology. As R ~. e s i~l t , tilesc countries could set up thc ncccssary il~fi*astructu~-e to plan a n d devclop human resources, institutions and funding early enough to take advantag(! of t l~c s u b s c q u c~~t rapid expansion in biotechnology that took plt~ce jn the 1980s and 1990s. For a long time inIndia, the only institutes engaged in advanced experimeutal biological research were theIndian Institute ofscience-Bangalore, the National Chcmical Laboratory -Pune and the Department of Applied Chemistry -Calcutta. In 1981 the Centre fbr Cellular nndMolecular Biology ( CCMB ) was set up in Hydcrabad by the Council of'Scientific and Industrial Rescarch and a fkw years 1ai;cr tbc National Iilstitutc of Imrnui~ology [NII) \vr?s O~C I I C C~ i n New Dcil~i by thc Depnrtme~lt of'scjence and Technology. In the Illdia116;th iivc yczudcvclopmcnt plan (1980)(1981)(1982)(1983)(1984)(1985) priority arcas for research irl iilh sciences, including Biotechnology, w e i t explicitly incl~ded.'~ In the 7th pian ( 1986-1990 ), i cmphasis in thesc areas was shifted to human rbcsoul-ccs dcvclopmcnt, pryjects iilvolving several discipli~~es and oesearcll and devclopnlent into biotcch.nology derived products. Ambitious programmes in biotechnology were also included intlie 8 t h f ve-year plan( 1991-1996 1. As early as 1982, aNation~lBiotccl~nology Board t NBTB ) was set u p in India for which the Department of Sciei~ce and / Technology provided sccr-ebarial services. The aim of this initiative was to 1; coordinate the research and dcvelopmcnt carried out in various ministries or scl-vices e.g. the Department of Science and Technology, the India11 Council oi' Medical Research, the Indian Council ol' Agl.icultura1 licseu~~ch a n d tllc Universi1;y G~. n n t s Commission. The NBTB drew u p a long tel.nl ])la11 fbr the developmcllL ol'Biotecknology in India bascd on acl>icvi\~g food scli-sufiicie~lcy, better health a~c i hygiene, ctlvironmental protection a n d industrial growth. A few years after its creation, in 1986, the NBTB was replaced by a separate government department, the Department of Biotechnology (DBT), heacled by a Secretary who reported directly to the Prime Minister. Dr. S. Ramachaadran who headed the new Department, played a Bey role in the subsequent farrcaching achievements of India in the field of Biotechnology. Among its 1.ecent acco~nplishments was negotiating the locatioll of' a part of the I~ltcrllational Centre for Genetic Engineering and Biotcchnology (ICGEB) in New Delhi. The ICGEB Iabol~atories functioned for several years in laboratories provided by the NII, belbre moving. to their ow11 campus nearby in 1997. l'he ICGER is anCicjpatcd to play a major role in the development of Biotechnology iin India. Tllc budget for the DBT in t h e 7th five-year plan was U.S. $200 million. Among the programmes supportedby DBT that have since made substantial accompl~shments are: -development of larval ii~secticides against mosquitoes extraction of low grade copper ore by bacterial leaching tissue culture propagation of bamboo, coconut and cardamom optimisiilg ethanol production increased production of' antibiotics locally production of insulin Large agribusiness firms such a s Agroceres SA were involved in biotechilology research and developn~ellt c.g. hybrid seeds, diseasc fi-ee potato tubers etc. Regional cooperation i n Biotechnol.ogy has been strong with the cstablishn~ent of the AT-gcntina-Brazil Centre fbl. Biotecllnology that initially dealt wit11 application of imlnobilised enzymes fur illdustrial production. Several institutions throughout the country, some fhndcd. by States, and others by the Federal Govcrnrner~t, have beell engaged in biotecl~nolugy research and development. h Bio-Rio Science-Industry Park was set u p in 1989 in Rio de Janeiro, supported by the Federal Government, the city of Rio and private sources. The P a r k aimed to generate U.S.$250 million worth of annual sales in the year 2000. The main objectives of the Park werc: -integration of basic and applied research in biotechnology technology developmcnt and transfer development of bio-industry with priority to health, agriculture, cocl.gy and the envil.onment manpower training promotion oi'tcclu~ology based joint vcntul-es The private sector in Brazil h a s been very active in Biotechnology. For example, Agroccres SA, a large agro-industrial corporation created i n 1945 is presently engaged in plant genetics research, the production of hybrid seeds, animal breeding and development of animal feedstuffs among other biotechnology activities.
In t h e U.S., E u r o p e and J a p a n , private sector cornpallies llavc m u s h~o o o l e d t o t a k e a d v a n t a g e of t h e major new discoveric?~ being m a d e j,n u~~i v~r s i t i e s and i.eson~.ch institutes. O f k n t l~c s e have been f'ou~~dcd by the reseax-cilcrs invol.ved i u making h e discove~*ies. Biotech1101 ogy con1 panics such a s Genetech achieved listing on the stock exchange to illcrease thcir assets and capabilities. These companies in t u r n began to fund research relevant to Biotcchr~ology in their own laboratories and sometimcs in univcrsities. Such research activity in private firms h a s developed into a major sour.cc of new products for Biotechnology. However, the governments in these countries have col~tinued to support t h e dcvclopment of' Biotecl~nology through public sector funding. In th.e U.K. for example, t h e abolishnlc~lt of the old Scicncc Research Cour~cil was accompanied by the creation of' a Biotcchnology and Biological Sciences Rescarch Coullcil to fir~ld academic research in t h e co~ultry. Them is intensc competition anlollg compauies to patent comme~'cially usc/'ul findings and t h e P a t e n t Offices h a v e sometimes not been able to 11nncIle t h c complications. This isillustratedfor examplc by the current legal battle over the comrncrcial use of the breast canccr related antigens, BRCAl and BItCA2, in the U.S. between the companies Oncormed and Myriad ."Advances i n Biotechnology have also led to heateddebates on ethical aspects e.g, t h e patentability ofhuman gene sequences or the experimental use of techniques t h a t might lead to cloning of h u m a n beings, a n d c~~v i r o i l n z e n t a l safety e.g. t h e development of cereals carrying genes ibr herbicide resistance that allow a n casy way of eliminating weeds in the crop but which might also allow the transf'e~. of' thc resistance gcnc to related wild relatives of' the genetically engincc~~ecl plant. Eiotcchnology has also reccntly nli~deiul-oads into the more traditional chernic:il industl.ies. T11.e use of' micr.oorganisms and plailts ibr removi tlg e u v i r o i~m e~~t a l pollutauts ranging from heavy metal ions to complex aromatic compounds i s becom-ing commolzplace. Microorganisms are also being used to conceiitrate gold From lo\v'-grade ort:s. to facilitate subsequent purification of' tllc metal.

BIOTECHNOLOGY IN SRI LANKA
Biotecbnolog~cal activities concerned with breeding rice have beell carried. out for many years in the Research Centres of the Agriculture Depal-tment. Several high yiclding varieties, developed mainly by coi~vel~tional breeding techniques, now account fbr more t11~111 95% of the rice grown in the island.' Vaccine production a t the Medjcal lZescarcli Institute, h o d technology at thc Ceylon Institute of'Scientific and Industrial Resea:~*ch and brewi1.1.g of' beet. may al.so be rcjisn-clecl. as fi-inge biotcchnology activities that have been ongoing (01: scvcral clecacles. Plant tissuc'cult~~re was initiated as a biotcchnology activily in 1976 by the Dcpartrnei~l; ol' Ag~.iculture for the clonal propagation of' ol.chicIs ant1 arlthui-ium. In 1984 a tissue culture laboratory was established at; the Central Agricultural Research Institute with the assistance of the Food and Agri cu.1 tural Organisation f'or the micropropagation bf fi-uit crops such as pineappl.e, citlws, banana, passion fruit and papaya4. Mass micropropagation of potato using mel-istem culture of disease fisee plants has been undertaken a t the Regional Agricultu~.al Rescardl Ccntrc at Bandarawela since 1987. The Plant Genetic Kesour.ces Ccntrc establiutled with Japancse assistance in 1958 I) as advanced facjiitics to u~ldcl~talte biotcc1:lnology research. 11.1 uitro co~lservatio~~, oI'1,oot ancl tuber crops, callus cu.ltu~.c and plant regeneration studies on rjcc arc sutne work undertaken at this ccntre. Some of'thesc recommendatiotls have become feasible because a loan has reccntly been made available for the development of biotecbnology from the Aslan Devcloprnent Bank (ADB). The 1997 ADB corlsultative rcport" also drew attention to shortcomings in the teaching of Biotechnologyrelated subjects a t universities, the need for training scientists and the requirement for large scale infusion of government funds to stimulate biotechnology in the country. The Committee recognised that equipment needed for Biotechnology are, in general, scarce and expensive. Also reagents for Molecular Biology such as restriction enzymes are unusually expensive materials. Therefbre the average Biotechnology grant involves greater expenditure than grants in other fields. In 1995, the funding fbr research in Biotechnology increased substantially over the previous three years ( Figure 2 ). This was made possible because of a general. increase in funding made available to NARESA consequent to the representations made over several years to different governments. In allocating funds for different projects the Committee was guided by the fact that Biotechnology had to be established almost from scratch, and therefore, in the beginning a t least, some flexibility was needed in interpreting a project as Biotechnology. As expertise and interest i n Biotechnology increased, the criteria for selection would progressively become more focussed on' developing new processes and products. I11 this context, projects with a significant component of' molecular biology techi~iyues have sometimes been referred by other NARESA Steering Committees to the Biotechnology Committee for funding purposes due to an absence of the required molecular biological expertise in such Committees.
Research funding for Biotechno!ogy In conclusion it may be said that the NARESA Steering Conlmjttec on Biotechnology has had a very significant effect on establishing thjs important field in universities and research institutes. Thjs is evident from the large number of presentations made i n recent years by grantees a t various scientific meetings, notably a t the Sri Lanka Associatiol~ for the Advancement of Scierlce annual sessions. At least five papers have also been published 111 jouruals such as Biochemical Biophysical Research Communications, Biochimica Biophysica Acta, Bulletinof Entomological Research, International Journal of Biochemistry and Cell Biology, and the Journal of the National Science Council of Sri Lanka. Six research projects have been completed to-date and this has resulted in the award of two PhD degrees based on work supported by NARESA grants.

PROBLEMS AND PROSPECTS
The Steering Committee has addressed many issues related to the safety and ethical aspects of Biotechnology work. Since there is no government body a t present with expertise to monitor the import of genetically modified organisms, the Committee agreed to do this as a n interim measure. The import of microorganisms from foreign countries for biological treatment of waste poses certain problems that the committee discussed often. Thc Committee also advised on the establishment of' new quarantine regulations and proposed that a new quarantiize service modelled on the Australian Quaralltinc service be sct up to moilitor importlexport of all plant, anilnal and microbial material, including genetically moddied organ] sms.
The Committee also advised on developing guidelines for collaborative research with foreign scientists involving local biological material .that could have implications for ii~tellectual property matters. Ex-pert advice on intel.lectual property rights in Biotechnology will assume greater importance in the future. Attempts have been made recently in the U.S. to patent plant products that have been traditionally used for centuries in South Asian countries for the same purposes. For example, scientists in the University of'Mississi.ppi were granted a US patent ill 1995 on the use of turmel-ic for healing wounds, wllen it; had been used in Ayurvedic medicine for this purpose for centuries i11 South and Southeist Asia. The patent was withdrawn after its novelty was subsequently challenged by the Ind.ian Couilcil for Scientific and Industrial 12esearch.
The development of techniques for cloning sheep and other mammals from embryonic and differentiated cells in 1996-1997 again provoked world.wide consternation about similar techniques being used to clone human beings. This is not an issue fhcing Biotechnology in Sri Lanka in tke near future since facilities and resources using this technology are presently not available. However, theNARESASteering Committee on Biotechnology Ilas to be prepared to face this and other similar issues in the long tcrm. The face of Uiotechnology is changiug-rapiclly, perhaps more so than in any other academic-industl-y ii~terf'ace. To keep abreast ol' these, to advise government through NARESA, according1.y requires that Committee members keep abreast of the latest developments. After many years of effort, membership of the ICGEB was achieved in 1994 for Sri Lanka. ICGEB is a fully fledged UN body. Membership provides access for local scientists to aninternational database inBiotechnolo~y, expertise of well-known scientists, training opportunities and regular update meeti.ngs. Furthermore the ICGEB helps member countries draft legislatioli on iiltellectual property, release of genetically modified organisms etc. that are of illcreasing relevance to this country. NARESA is the focal point for the ICGER i11 Sri Lanlta and the NARESA Steering Committee on Biotechnology is a critical feature of this link.