Plant Biotech Blog

C Kameswara Rao
Foundation for Biotechnology Awareness and Education
Bangalore 560004, India
pbtkrao@gmail.com

The US Food and Drug Administration (FDA) routinely and stringently used the ‘Principle of Substantial Equivalence’ (PSE) for decades to assure the public of the safety of foods and drugs marketed in the US. PSE refers only to the product and not the process of its production. On account of the high standards of FDA’s regulatory oversight, most other countries generally approve drugs and pharmaceuticals on the basis of FDA’s approval.

In the context of modern agricultural biotechnology, antitech activists have repeatedly made PSE an issue of serious concern.

Efforts are made in every country to demonstrate that a genetically engineered (GE) variety (transgenic) and its products are ‘substantially equivalent’ (SE) to its conventional variety (isogenic) and its products, but for the new genes (transgenes) in the transgenic variety and the consequent expected products of the transgenes. Once SE is established, the FDA requires no further regulatory review.

Under the ‘provision for voluntary consultation’, the US biotech companies seek SE certification by FDA, of all GE varieties and their products they intend to market. The product developers submit to the FDA, voluminous dossiers on the safety and risk analysis of the GE varieties and their products developed by them. These data are usually confined to the comparative study of proteins, carbohydrates and other components of nutritional significance. The focus is on determining whether the new GE varieties and their products are toxic or allergenic. If some GE products contain miniscule quantities of a few additional components that are a) broken down during food processing or digestion or b) if they occur below acceptable independently determined threshold levels, the products are regarded as ‘Generally Recognized As Safe’ (GRAS).

The presence of new genes that would code for fats, proteins or carbohydrates in the GE products that may be toxic or may cause allergies or may adversely affect the nutritional value of the product, prevents certification as SE or GRAS, without additional appropriate and adequate testing.

Products from GE soybean, tomato, corn, cotton, etc., on the US markets have been tested extensively, much more than any conventional foods, and judged SE to their conventional counterparts and so are safe food and feed.

The policy of the FDA did not result in any health concerns and over 350 million US citizens who have been consuming GE food products for about 13 years are a living testimony of their safety. Nevertheless, the FDA policy has been criticized on account of, a) the FDA itself has a mandatory process for approving transgenic animals, b) the US Environment Protection Agency (EPA) and the US States Department of Agriculture (USDA) have a mandatory and open process for evaluating the biosafety of GE crops, and c) the data are provided by the product developers.

Labelling GE products as SE or GRAS is not mandatory in the US, but there are persistent demands for labelling in several other parts of the world. This leads to considerable confusion and controversies, more so if PSE has to be applied to all products of GE, including livestock feed, and worse if SE has to be established for different transgenic varieties of the same crop with the same transgene, as demanded by some activist groups.

In the application of PSE, the comparison should only be between the GE variety and its
isogenic, which is the basic variety into which a new gene was inserted, but not any and every variety of the same crop. The certification is to the effect that the GE crop variety is substantially equivalent to its isogenic, in genotype, marked characteristics and performance, but for the transgenes and their anticipated products and characteristics. If the isogenic were safe, the transgenic would be equally safe, provided that the newly introduced transgenes do not exercise any adverse effects by themselves or through altering the expression of any other genes of the isogenic in the new status which may happen very very rarely. Such an assurance requires scientific evaluation of the crop variety and its products, which involves additional effort, time and expense, that escalate consumer costs.

The US practice of agricultural biotechnology companies voluntarily submitting detailed dossiers on the safety and risk analysis of the GEOs and their products, developed by them before they are marketed should be global, although the activists look down upon data provided by the product developers themselves, even when gathered by different recognized laboratories outside the companies. When testing standards and procedures in different countries were reasonably uniform, what is considered safe in one country should also be considered so in the other countries. This will eliminate the need for repeating the same and every test in every country, saving time and expense.

At no time, transgenics can be wholly SE to their isogenics in their entire genotypes and this is not related to transgenic technology. Even to start with, members of the same population are not entirely genetically identical. In addition, mutations occur naturally and randomly, involving different genes. Lethal mutations are naturally eliminated. Mutations of the genes of the desired characteristics are eliminated in the process of selection, but those that do not affect the desired characteristics escape attention and accumulate. After a certain number of generations, a critical genetic analysis will contravene SE, although SE can be established for the genes of the desired characteristics. Such a situation would cause problems in some countries, where the
regulatory authorities apply the principle of SE more in letter than in spirit, and a lot
more strictly than in other countries.

The official consensus of the European Union (EU) is that, SE should only be used to inform of basic safety assessments and so GE products require further confirmatory analysis by sophisticated methods. The EU safety regulations, based on this premise, are so stringent that they raised doubts whether any GE product will at all qualify to be considered safe.

The Codex Alimentarius Commission (CAC) is the international organization established in 1963, jointly by the FAO and WHO, under the Food Standards Programme to set international guidelines for food standards and safety. Comprised of 165 member countries, the CAC sees SE as a starting point in the regulatory process rather than as the end point.

Notwithstanding the importance given to PSE, it has been criticized as vague, ill defined,
flexible, malleable, open to interpretation, unscientific and arbitrary.

In the debate on SE it is often held that,

a) the focus of SE has been well known nutritionally significant components, occurring in significant quantities,
b) the studies employed routine food safety testing methods which are not sensitive enough to detect all components and are not detailed total critical analyses,
c) that more sophisticated and deep analytical approaches may reveal chemical compounds hither to unexpected and unknown, which may make the GE products unsafe for human consumption, and
d) in the US, SE data were generated not by independent entities but by the product developers themselves (and so suspect) and largely remained in the private domain, not easy for others to access for evaluation.

Metabolomics is an area of sophisticated but complex ‘fingerprinting’ procedures that provide for a detailed profiling of all products of metabolism in a cell. Metabolomic studies by Catchpole Gareth and 11 others in 2005 demonstrated that, apart from targeted changes, field grown GE potatoes and their traditional cultivars were SE to each other. The minor differences that were found between the GE and the non-GE varieties were of the same kind and magnitude of such differences among the non-GE varieties, that occur on account of natural variation in gene expression. None of these differences are significant in the context of the safety of the GE potatoes for human consumption. This study is safe from all reasonable criticism.

Some activists groups demand sophisticated and complex procedures to establish SE, but such procedures entail time and money escalating consumer costs and so cannot be routine methods of establishing SE. They should be used only if there was justification, perceived from standard analyses, to go for more intensive methods.

Invoking SE, which relates only to food and feed, in issues of non-target organisms such as the aquatic arthropod Daphnia magna with reference to MON 810 Bt corn, as was done last year, is tantamount to shifting goal posts. There are other mandatory procedures to assess the impact of GE crops and products on non-target organisms and the environment.

There is a dire need for a uniform and harmonized international policy on SE. On account of the concerns raised, the PSE should be re-examined, for re-defining its applicability to GE crop plants and their products, laying emphasis on a reasonable application of the principle, addressing only those genes and their products that are relevant to the objectives of developing a particular transgenic variety or product.

At the moment, there is no evidence that SE is an issue that adversely affects the safety of GE crops or their products as food and feed.

C Kameswara Rao
Foundation for Biotechnology Awareness and Education
Bangalore, India
pbtkrao@gmail.com

Presently, Bt cotton containing the Cry 1 Ac gene from the bacterium Bacillus thuringiensis is the only commercialized genetically engineered (GE) crop in India. As per a report on the ‘Global Status of Commercialized Biotech/GM Crops:2008’ published by the International Service for the Acquisition of Agri-biotech Applications, the cultivation of Bt cotton in India has increased from 0.5 mill ha in 2002 to 7.6 mill ha in 2008, which strongly indicates that the Indian farmers have ignored the activist noises and accepted the technology for its benefits. In the period from 2002 to 2008, Indian Bt cotton scenario changed rapidly in terms of the number of Bt farmers, approved hybrids (three to about 150), transgenic events (one to five) and seed companies (one to over 30). During this period, farmer profits increased between 50 to 110 per cent, yield increased between 30 to 60 per cent and the pesticide use reduced by over 50 per cent, benefiting about five million resource poor farmers. The country has greatly enhanced its cotton production and export.

The antitech activists have now sensed the loss of their protracted battle against Bt cotton, and shifted the focus to Bt brinjal (aubergine, egg plant) and other GE vegetable crops. Bt brinjal containing the same Bt gene Cry 1 Ac as in cotton is developed against the shoot and fruit borer of brinjal that causes enormous losses both to the farmer and the consumer. Bt brinjal is awaiting the approval of the Genetic Engineering Approval Committee (GEAC) for commercial release. If Bt brinjal is successful and finds favour with the farmers and the consumers, several other Bt crops now in advanced stages of development would be commercialized and the major battle to prevent GE food crops from becoming an important component in the Indian agriculture would be lost.

The activist groups have filed two ‘Writ Petitions’ (WP) in the Supreme Court of India (SCI), demanding a moratorium against the development of GE crops. The activists intend to halt the regulatory process, so that this will preclude commercial release, not just for the period of moratorium if sanctioned by the SCI but several years after it was lifted later. They also insist on implementation of regulatory tests, designed by one of their science faces, which was said to take some 20 years to complete, so that the process of GE crop development in India would be halted for over a quarter of a century. In either case it would be a death knell for GE crops in India which is certainly against the interests of the country.

The stand of the activists smacks of double standards, as they have not been visibly against biotechnology in pharmaceutical or other industries which constitute an influential segment.

Fortunately, the SCI has adopted a balanced view and earlier permitted field trials of certain GE crops. During the hearing of the WPs on April 29, 2009, the Bench observed that ‘GM seeds could possibly be a means to eradicate hunger and poverty. Poverty is probably more dangerous than the side effects of GM seeds’.

On the submission by the Petitioners, the SCI Bench suggested an intense working of the existing regulatory regime and asked the Government to consider setting up of a National Centre for Assessment of GMOs. The Government rightly replied that ‘there are already several laboratories set up in various Universities (and research institutions) which are doing research work on GM’. Over a dozen public sector and other institutions are involved in biosafety evaluation of GE crops, supervised by the Review Committee for Genetic Manipulation (RCGM) before the GEAC takes the final decisions on the open field trials and commercialization. It is impossible for any single centre to handle the entire biosafety regulatory process as it requires diverse areas of expertise.

The Petitioners seem to have also suggested constituting an expert committee on lines of a 1997 Committee for the regulation of hazardous wastes constituted on the orders of the SCI, but this is superfluous and wholly irrelevant to GE crops.

Activists also constitute political pressure groups as politicians consider them as vote banks. Obviously disappointed with the results of their anti-GM campaigns, which have not so far yielded the desired results, the activists sought the support of the political parties, taking advantage of the recent general elections. As reported widely in the Indian Press on April 30, 2009, except for the Congress party, the leading member of the outgoing United Progressive Alliance (UPA) Government, all the other parties fell in and expressed anti-GE sentiments in their election manifestoes. The political parties might have considered it expedient to accede to the activist demands in return for electoral support. In an extremely volatile electoral situation where no party was confident of its poll prospects, the chances of coming to power and to be bound to a pre-poll promise were bleak. The statements of the political parties do not sound total opposition, but that GE crops would not be allowed ‘without full scientific data on long term effects on soil, production and biological impact on consumers’, as the Bharathiya Janatha Party, the lead member of the National Democratic Alliance (NDA) proclaimed. This implies the lack of scientific data on the safety of GE crops in development, which is not true and reflects the ignorance or deliberate indifference of these parties to the biosafety regulatory process in India which is among the very stringent regimes in the world. Then how long is a ‘long term’? Even now biosafety evaluation takes a minimum of nine years, which is actually longer than necessary. The major objective of current procedures of biosafety evaluation is to ensure that GE products are safe to the consumers and the environment. How does one assess long term impact on consumers directly? Some parties demand labeling of GE foods, which is not a bad idea even if it is difficult to implement in a country dominated by scientific illiterates, which includes the activists, the politicians and the media.

The Communist parties are more retrogressive. The Communist Party of India (Marxist-Leninist; CPI M-L) said that no GE crops should be introduced and field trials should be halted immediately. The Communist Party of India (CPI) wanted a moratorium on GE crops and favours organic farming, which would take the country backwards by some 50 years. Both the Communist Party of India (Marxist; CPM) and CPI would scrap the India-US Knowledge Initiative on Agriculture, if they come to power, which is a dream, when they lost their position as pressure groups which they enjoyed with the UPA Government, till the show down on the Indo-US Nuclear Agreement last year and now totally out of reckoning. The Indian Communist parties seem to forget how strongly China, the life spring of their ideology, is committed to GE in agriculture to a great advantage, which for no valid reason the leftists want India to lose.

The miniscule regional parties in Tamil Nadu joined the chorus of ‘no GE crops’, reflecting localized ignorance.

The glaring dishonesty of the political parties lies in that they have been coalition partners in the earlier NDA Government or the outgoing UPA Government or both, and under the Principle of Collective Responsibility of the Cabinet or as supporting partners of the respective coalitions, they have been a party to promoting research and development of GE crops in the country for over a decade. For political gains they now sing a different tune.

By providence all the parties that declared an anti-GE stand lost in the elections (of course not for that reason) taking the wind out of their stated opposition to GE crops. In the reconstituted UPA Government Agriculture stays with the same Minister who supported modern agricultural biotechnology. The Ministers for Science and Technology, Environment and Forests, Health and Family Welfare, and Commerce and Industries, concerned with biotechnology in one or the other way, are all from the Congress party, giving hope for a continued promotion of GE crops, though it is difficult to predict the swing of the political pendulum to the other side.

For one thing, soon the National Biotechnology Regulatory Authority (NBRA) Bill will sail safe through the Parliament to become a Law, which will inspire public, political, professional and media confidence. The NBRA will also convince the SCI against imposing a moratorium on GE crops. But the activists would continue their tirade even after losing, so long as funding would be available.

A country’s science policy should be framed by its scientific fraternity and managed jointly by the relevant scientific institutions and the appropriate departments of the Government but not by vested interest that uses junk science to pursue inept politics, often with support from foreign agencies. The new Government should ensure this.

C Kameswara Rao
Foundation for Biotechnology Awareness and Education
Bangalore, India
pbtkrao@gmail.com

The theme of the recent conference of the Biotechnology Industry Organization (BIO) in Atlanta, USA (May 18-21, 2009) with about 14,500 participants, was ‘Heal, Fuel, Feed the World’ where over a dozen diverse sessions were organized on biotechnology in food and agriculture, which did not leave many concerned with agricultural biotechnology wholly satisfied.

The BIO annual International Conventions are the largest global event for the biotechnology industry ‘to provide insights and inspiration on the major biotech trends, technological innovations and policy issues that affect the industry’.

Basing on the experience of the earlier BIO conferences, Henry Miller and Gregory Conko wrote in June 2004 that in the BIO conferences ‘the biopharmaceutical sector is for the most part robust, (but) biotechnology applied to agriculture, food production and environmental problems has a long row to hoe’. The Indian situation now seems to be much worse.

Bangalore Bio (BB), an annual event since 2001, organized by the Karnataka Vision Group on Biotechnology (KVGB), the main pillar of BB, with solid patronage from the Government of Karnataka, is a poor imitation of BIO conventions. The Association of Biotechnology Led Enterprises (ABLE), which in its own words a ‘collective face of Indian biotech industry’ is a powerful supporter of BB.

BIO works throughout the year to create a policy environment that enables the industry to continue to fulfill its vision of bettering the world through biotechnology innovation, while BB wakes up only to organize the annual ceremony.

BB did have some conspicuous component of agribiotech on its programme during the previous years. There were well received Public Lectures on agribiotech which were missing from 2006 and onwards. Even at the 2008 BB meetings there was an ‘Agribiotech Day’ focusing on four areas, with Avesthagen, Metahelix and Indian Council of Agricultural Research as partners.

The BB’s 2009 brochure proclaims ‘Biotechnology beyond boundaries–the promise of India’. and ‘India’s biggest biotech show’. Yet, disturbingly, agribiotech has gone out of the sights of the KVGB and is totally missing from the 2009 programme of BB as also the agribiotech partners of earlier years, chiefly Avesthagen and Metahelix (Monsanto has withdrawn from BB conferences some years ago).

ABLE is heavily biased towards the pharma and industrial biotech sectors. Biospectrum, a much visible biotech business magazine is also heavily skewed towards the pharmaceutical industry, but Biospectrum cannot be charged with a total neglect of agribiotech.

The 7th Biospectrum-BLE Biotech Industry Surveylisted 282 biotech companies (Biospectrum June 2009). There are 30 agribiotech and 53 plant biotech (whatever this means) companies. There is only one nanobiotechnology (an area of genuine modern biotechnology) company, and stem cell research companies were not identified. Thirty eight companies are involved in bioinformatics, an area of biotech only by extension. Some one should explain how 53 companies that do only clinical research and trials qualify to be classified as biotech companies, unless the hiccup is in the use of the terms ‘biotech’ and ‘life sciences’, which cannot be used interchangeably. How many of the remaining 107 companies qualify to be classified as truly biotech, meaning modern biotechnological concepts, protocols and tools? Dr Krishna Ella said that ‘by strict definition of biotech, which is recombinant, the Indian vaccine market is only about Rs. 1,000 to 1,600 crore, including the sales of the MNCs’ (Biospectrum Juy 2008). Obviously, the majority of the pharmaceutical and industrial sector companies operate on the basis of age old technologies but jumped on the bandwagon of biotechnology to garner publicity and benefits. Against this, one wonders why AMUL and United Breweries find no place among biotech companies, when they are heavily into fermentation technology.

During 2008-09, of the top 10 Indian biotech companies two (Rasi Seeds and Nuziweedu Seeds) are agribiotech. During 2007-08, vaccines contributed to about 47 per cent (Rs. 3,265 crore out of the total biopharma revenue of Rs. 6,900 crore), while therapeutics (36 per cent) and diagnostics (17 per cent) constituted the rest of pharma market and all this is not from legitimate biotech. In comparison the market share of agribioetch was about Rs. 1,200 crore, which is certainly considerable, though the vast majority of the agribiotech companies are sub-licensees of the gene constructs and only very few are actually involved in R & D.

It is a serious lapse on the part of BB 2009 to ignore agribiotech, an important component of the Indian biotech enterprise.

The agribiotech industry has not been projecting itself adequately and has to take considerable blame if it is ignored. The All India Crop Biotechnology Association (AICBA) comprised of agribiotech companies is comatose and never did anything visible or effective in support of the agribiotech sector. The handling of antitech activism by the agribiotech industry has been very sloppy. They should have impleaded in the Supreme Court of India in the two Writ Petitions that are seeking a moratorium on GE crops India, which would have supported the Government’s efforts to oppose the petitions. As the companies were not made a party in the WPs, they did not bother.

“Miss it! If you don’t belong to Biotech sector”, the organizers of BB 2009 said. Agribiotech missed it. Is it because the KVGB and ABLE, are finally convinced that agribiotech does not belong to the biotech sector?

Why did not the agribiotech companies stand up against this insult or do they see only diminishing returns from their investment in BB and kept quiet, if the decision was theirs?

This is unfortunate, at a time when the agribiotech sector is facing severe problems, which the pharma and industrial sectors do not. This is the time for the unity of all biotech sectors in the country and not for divisive politics. Together they can address several important issues like getting the National Biotechnology Regulatory Authority on the book and standing up to the ill considered opinions being expressed by the new Minister for Environment and Forests against genetically engineered food crops such as Bt brinjal.