genetic engineering

The battle of the transgenics

Controversy about RR soybeans heats debate about biotechnology

EDUARDO CESAREmbrapa owns the technology of the IMI soya that has a gene from BasfEDUARDO CESAR

There are signs that the controversy over allowing the planting of transgenic soybeans for the 2003/2004 crop, in Rio Grande do Sul, are already endangering the enormous potential for the development of biotechnology in the country. The debate, impassioned and heated, does not distinguish between the product – in this case, Roundup Ready (RR) soybeans, from Monsanto – and the technology for producing genetically modified organisms (GMOs). Nor does it take into account that this same technology is, for example, the basis for the production of the insulin widely used by diabetics, of the vaccine for type B hepatitis, of growth hormones that stimulate infant development and up to 80% of the cheese available on the domestic market, since chymosin, an essential component of curds, is obtained by modifying the Escherichia coli bacterium, just to mention a few examples. “The polemics condemn technology as a whole”, warns Fernando Reinach, the president of Alellyx, a Brazilian biotechnology company, linked to the Votorantim group.The GMOs – amongst them, RR soybeans – are organisms whose genetic material has been modified by the introduction of one or more genes from another species, previously selected and with a specific goal: conferring advantages on the product. The RR soybeans, for example, the star of the season, was modified by the introduction of the cp4-epsps protein, which, incorporated into the plants genetic code, endows it with tolerance to glyphosate herbicide, reducing the need for using this agrochemical and lowering costs for the producer.

The same technology is used in the production of insulin for the treatment of diabetes, a disease that affects 6% of the world population. “Producing insulin from the pancreas of cattle and pigs would not be able to meet the demand, and the product cloned by transferring the human gene to a bacterium makes it possible to produce human insulin in great quantities at lower prices, and even to get modified insulins that are more effective”, says Isaias Raw, the president of the Butantan Institute Foundation. “And diabetics are not complaining about the transgenic insulin that saves their lives.”The same occurs with the vaccine against type B hepatitis, Raw notes. The natural vaccine used to be produced from the few defective viruses, without DNA, that appear in the blood of the victims. “It would be rash to guarantee that this vaccine does not transmit hepatitis”, he observes. Today, it is possible to produce the protein wrapping of the virus, without DNA – and hence incapable of reproducing and causing the disease -, in transgenic yeast. The Butantan Institute produces this vaccine, which is given, free of charge, to all Brazilian newborns and youngsters. “This means 34 million doses produced, which prevent new infections that nowadays affect over 3 million Brazilians”, he stresses. The vaccine against type B hepatitis, from the Butantan Institute, opens the way to new vaccines and medicines. “If a vaccine against Aids arises, it will certainly be transgenic”, he forecasts.

Transgenics against short stature
Also transgenic is the growth hormone (hGH) against short stature, a condition that affects 10,000 Brazilian children. The gene that encodes the molecule of the hormone produced by the pituitary gland, located at the base of the brain, is cloned and modified, to be introduced into a bacterium, usually Escherichia coli. A sequence is taken out and inserted into a molecule of bacterial DNA, the plasmid, which starts to produce the hGH in the bacterium. The result (see Pesquisa FAPESP 82) is a hormone identical to the one made naturally by the human organism, according to Paolo Bartolini, a partner in Hormogen – the company that holds the Brazilian patent of the hGH, supported by FAPESP, under the Small Business Innovation Research Program (PIPE) – and head of the Molecular Biology Center of the Institute of Nuclear Energy and Research (Ipen).

Biotechnology is now used in the United States, Canada and the European Union to produce the coagulation factor – known as Factor VIII, fundamental in the treatment of hemophiliacs – exempt from contamination, using mammal cells. Brazil still imports the Factor VIII produced by means of the purification and fractionating of human plasma, at an annual cost of US$ 120 million. “This method brings risks that have to be eliminated in tests on the plasmas of origin”, explains Marco Antonio Zago, from USP’s Ribeirão Preto School of Medicine and the coordinator of the Cell Therapy Center, one of the ten Research, Innovation and Diffusion Centers (Cepids) maintained by FAPESP. “We have expectations that Brazil will shortly be ready to produce this coagulation factor.” On the list of transgenic products used in medical practice, Zago also adds erythropoietin, a hormone used in the treatment of anemia, which, until recently, had to be isolated from urine and nowadays can be produced using genetic engineering.The efficiency and success of transgenics in the medical area prompts a query from Raw: “Why is it that vaccines, hormones and enzymes, administered to the great majority of the population, are not questioned? Why soybeans? What is the rationality in that?”

Beans immune to viruses
In agriculture, biotechnology and GMO technology have an enormous field. The Brazilian Agricultural Research Corporation (Embrapa) is developing various lines of research with transgenic plants, with the objective of offering producers alternatives for reducing costs and achieving greater competitiveness. The list of products at the research stage is immense: it ranges from genetically modified cotton immune to insects – like the caterpillars and weevils -, then to corn, potatoes and papaya, and on to beans that are resistant to viruses, which devour the crops and the farmers income. In the case of beans, the main beneficiary is the small farmer. “The planting of beans is being abandoned, because the producers do not make any money”, explains Elíbio Rech, a researcher from Embrapa.

In universities and research institutes all over the country, the examples are multiplying. In the Federal University of Rio de Janeiro (UFRJ), researchers are investigating the genetic improvement of rice, with the objective of increasing its tolerance to pests, diseases, and adverse conditions of soil and climate. The Biotechnology Department of the Federal University of Rio Grande do Sul (UFRGS) is trying to identify antigens with potential for making up a recombinant vaccine against Boophilus microplus, a tick that reduces the production of milk and meat in herds of cattle and is a transmitter of the protozoa Babesia bovis and B. bigemina and of the rickettsia Anaplasma marginale , which causes tristeza or texas fever.

At the Luiz de Queiroz College of Agriculture, of the University of São Paulo (USP), they are studying a genetically modified variety of eucalyptus that had a pea gene inserted in its genetic code, which leads the plant to produce more biomass, increasing the yield of pulp. The research is of direct interest to Companhia Suzano de Papel e Celulose, a partner in the project, carried on in the ambit of FAPESP’s Partnership for Technological Innovation Program (PITE), in that the genetically modified eucalyptus, being more productive, may reduce the need for deforestation.

From this same perspective of investigation, FAPESP, in partnership with the Fund for Citrus Plant Protection (Fundecitrus), supported the project that deciphered the genetic material of Xylella fastidiosa, responsible for the yellowing disease – a feat celebrated by the Brazilian and international press -, funded the sequencing of the Xanthomonas citri bacterium, which causes citrus canker, sponsored the identification of 50,000 sugarcane genes, and, together with the Bela Vista Bovine Genetics Center, has started the Bovine Functional Genome project. As one knows, genome research is the first step towards implanting competence in the area of biotechnology, and it opens the way towards developing transgenic plants and animals, immune to diseases.

Research slowing down
The commotion that has been stirred up about RR soybeans, though, is endangering the advancement of Brazilian biotechnology. Embrapa’s project for improving beans is now well advanced, since there have now been three and a half years of intense work. But in spite of having the authorization of the National Technical Biosafety Commission (CTNBio) to go ahead with the studies, the researchers are not succeeding in getting from the other ministries documents required for carrying out field tests, the Temporary Registration (Ret) or the Operating License for Areas of Research (Loape). An identical obstacle is preventing the advancement of studies with potatoes. Recently, Embrapa was able to get the Loape, granted by the Brazilian Institute for the Environment and Renewable Natural Resources (Ibama), to carry on with its researches into the papaya.

Researches with grains have not met the same good fortune. Embrapa has slowed down its researches on IMI soya, another herbicide resistant transgenic plant that had been seven years under development, in partnership with Basf. “The IMI is in an improvement program, but the prospect for marketing it is a medium term one, on account of the lack of regulations”, Rech regrets. In the case of the IMI, Embrapa is the owner of the technology. Under the agreement, the Brazilian company participates with the germplasm, and Basf with the gene. “The plants are generated in Brazil with seeds from Embrapa. It is Brazilian technology with their genes”, Rech stresses.

In cooperation with Monsanto, Embrapa is also doing the tropicalization of the RR soya – since the multinational company’s product is only compatible with the soil and the climate of Southern Brazil, and does not adapt to other regions of the country. When it is possible to conclude the research, the tropicalized seed will be patented by Embrapa. “The technological importance of this contract lies in producing seeds that are going to bring down the production cost and guarantee sustainability on the foreign market for all the Brazilian producers of soybeans”, Rech emphasizes.The researchers from Esalq are facing similar difficulties. They will only manage to carry out field tests with the transgenic eucalyptus in the municipality of Anhembi, in São Paulo, after complying with a requirement of the Ministry of the Environment (MMA) and making a detailed assessment of its impact on the local flora, fauna and population. “This is not viable”, says Carlos Alberto Labate, from Esalq’s Genetics Department. “At this rate, we are going to end up having to import technology”, he foresees.

The price of falling behind
Slowing down the pace of research may cost the country dear. “We will have the genetically modified molecules, but without any tests. If the country allows the planting of transgenics, the producers are going to end up having to buy seeds from the foreign companies and pay them royalties for them. This is actually is what is now happening with the RR soybeans: the producers are paying royalties to Monsanto, while Embrapa now has herbicide resistant soybean seeds, without the possibility of testing them”, says Maria Lucia Carneiro Vieira, from Esalq’s Genetics Department, who is coordinating a group of researchers that is developing a transgenic passionflower that is resistant to the Xanthomonas bacterium and to the virus that causes the fruit to harden.

This “undeclared moratorium”, as Labate calls it, decreed by the absence of regulations, has been dragging on since 1998, in spite of the fact that Brazil has had, since 1996, a Law on Biosafety – number 8974 – regarded as one of the most advanced in the world, in the assessment of Reginaldo Minare, a lawyer specialized in biotechnology. The law lays down standards for the techniques of biotechnology, genetic engineering and the production of GMOs, with the objective of “protecting the life and the health of man, animals and plants, as well as of the environment”.

The country also has a qualified team, the CTNBio, created by Provisional Measure 2191, of August 23, 2001, whose responsibility it is to advise the federal government on the formulation and implementation of the National Policy for Biosafety relating to GMOs, to establish technical standards, and to issue “conclusive technical reports referring to the protection of human health, of living organisms and of the environment” for activities involving constructing, experimenting, cultivating, manipulating, transporting, marketing, consuming, storing and disposing of GMOs and their by-products. The CTNBio is made up of 36 members – 18 sitting and 18 substitutes – amongst them eight specials “of eminent scientific and technical learning”, besides having representatives of the Ministries of Science and Technology, Health, Environment, Education, Agriculture, Livestock and Supply, and of legally constituted consumer defense bodies, biotechnology companies and workers.

Report under suspicion
The commotion over GMOs started when the Consumer Defense Institute (Idec) filed a public civil lawsuit with the 6th Court of Federal Justice in Brasilia, contesting the competence of the CTNBio to waive the Environmental Impact Study (EIA) of the genetically modified soya, tolerant to the Roundup Ready herbicide, before allowing it to be planted. The lawsuit invoked the Law on the Environment, which, the argument ran, conferred this authority on the Ministry of the Environment. The lawsuit was ruled in Idec’s favor, and this meant the suspension of the CTNBio’s Report – published in Communiqué nº 54 – in which the commission concluded that there was “no evidence of environmental risk or risk to human or animal health” arising from the use of genetically modified soya, for which reason it decided to waive the EIA and manifest itself favorably for it to be marketed. Monsanto appealed against the court’s decision and obtained a favorable vote from the examiner of the proceedings in the Federal Regional Court, in a chamber made up of three judges. The assessment of the other two judges is still awaited.

Still being waged, the battle has opened up a legal hiatus that has ended up casting the soybean producers outside the law. And, to boot, it has disorganized the seed market, as it has become impossible to make a forecast of demand. In the 2002/2003 crop, for example, there was a shortage of soya seeds. The producers from Rio Grande do Sul turned to Argentina, where transgenic soya has been legalized: they imported and planted RR soya. At the beginning of this year, the harvesting and marketing of something like 10 million tons of soybeans had to be authorized by means of a provisional measure, since the production of transgenics had been suspended by a decision of the courts.The federal government – whose team, incidentally, is also split with regard to allowing GMOs -, then set up a commission made up by nine ministries, commanded by the Civil Office, to analyze the question of biosafety and formulate a draft law intended to put an end to the polemics over transgenics.

But even before the bill being forwarded to Congress, the government had to yield to the injunctions of reality – and to the pressure of the producers from Rio Grande do Sul who were threatening civil disobedience – and published a new provisional measure, this time authorizing the 2003/2004 crop to be planted. “This year, the area planted will be even larger”, foresees Antonio Sartori, the president of Brasoja, a grain broking company in Rio Grande do Sul.The legal imbroglio is far from being settled: the general public prosecutor of the Republic, Cláudio Fonteles, presented to the Supreme Federal Court (STF) a direct lawsuit alleging the unconstitutionality of the provisional measure that allowed the planting of the current crop, on the grounds that it infringes five principles of the Constitution.

Another two lawsuits were also presented to the STF: one from the Green Party (PV), and the other from the National Confederation of Workers in Agriculture (Contag). On the hypothesis – regarded by many as remote – of the Supreme Court considering the measure of the Executive as unconstitutional and banning the planting of this crop, the federal government will have to indemnify the producers: after all, the crop is protected by the provisional measure.The impasse is going to resolved in the courts or in the National Congress, which, at the beginning of November, is to vote the measure that authorized the planting of the RR soya, and then start to examine the draft law on transgenics that is being drawn up by the federal government.

From the vanguard to illegality
A quick balance of this long period of debates comes to the inevitable finding: the country has lost five years of research into GMOs. Ernesto Paterniani, full professor of genetics at Esalq, who in 1998 was a member of the CTNBio’s team of scientists, recalls that, at the time, besides analyzing the documentation presented by Monsanto, examining the nature of the protein and of the molecule of the RR soya and carrying out safety tests at the Jaboticabal School of Veterinary and Agrarian Sciences, of the São Paulo State University (Unesp) and at USP, the commission also recommended the monitoring of the areas to be planted for a period of five years. This measure, by the way, was accompanied by the European Union (EU), which is also assessing the planting of GMOs. But in the midst of the legal commotion, Brazil has left a position regarded as being in the vanguard to become entangled in a mistake: transgenic soya was planted illegally and is being marketed without any monitoring of the company that supplies the grain and without any inspection by the competent bodies, be they the CTNBio, the MMA or any other. “The country has passed from a situation of legality to another one, of illegality”, Reinach regrets.

Brazil has already proved that it has the competence, human resources and knowledge to stand out in the area of biotechnology of plants and animals, a technology that is being implemented in several countries, with the objective of improving the quality and resistance of the product and reducing production costs. Genetically modified products are a viable option for development, above all for Brazil, whose list of exports feature ten agricultural products, soybeans amongst them. “GMOs are, without a doubt, an important component in the cost of production, besides having as a target a reduction in the impact of agrochemicals and resulting in plants that are more resistant to drought and with a lower level of allergenic proteins, amongst other benefits”, argues Rech, from Embrapa.

The RR soya, for example, does not fight with weeds for nutrients from the soil, which guarantees the farmer greater productivity per hectare. Without the presence of these intruders, the combine gets clogged less, speeding up the pace of the harvest. More than this: when the seeds are mixed up with weeds, they get more humid, which obliges the producers to pay for the soybeans to be dried. Also: “The plants are more resistant and suitable for being planted straight away, without any need for plowing or turning over the soil. After the harvest, the organic matter remains in the soil, which, being more fertile, increases the population of worms and microorganisms”, Paterniani explains. And all this without, apparently, offering any risk to the environment: according to a report by CTNBio, soya is a predominantly autogamous species, whose rate of cross-pollination is about 1%, besides which it does not have any sexually compatible uncultivated parents in Brazil.

It is important to recall that Brazil produces 52.5 million tons of soybeans, a product that is also one of the highlights of the list of exports. The domestic market consumes something like 10 million tons, a little more than 30 million tons is crushed, and the other 21.5 million tons of the grain are exported. In the 2003/2004 crop, the production of the soya complex – grains, oil and meal – should come to 36.9 million tons, surpassing the American crop (34.6 million) and the Argentinean one (35.5 million), according to Sartori, from Brasoja. Exports will add up to US$ 8 billion, and Brazil’s participation in the world market has good prospects for growth. The tendency is for an increase in business with Asia, in particular with China, which, last year, imported more than 20 million tons of this grain, of which 40% from the United States and 34% from Brazil. “There is a market for soybeans that are transgenic, non-transgenic and organic”, Sartori notes. China, for example, buys any kind of soybeans, but it demands the product to be labeled. Business with Brazil, which does not use labeling, is guaranteed by an agreement that expires in April next year and which has a provision that the soybeans are to be identified from that date onwards. “Unless it lays down regulations, Brazil loses the Chinese market”, Sartori foresees.

Advantages for the producer
In the United States, according to data from the United States Department of Agriculture (USDA), roughly 80% of the soybeans, 38% of the corn and 70% of the cotton produced in 2003 is biotechnologically modified. In Argentina, Canada and China, the planting of transgenics has grown in the last few years. The National Center for Food and Agricultural Policy calculated the advantages of using GMOs for the producers: those who adopted the RR variety of soya failed to use 13,000 tons of herbicides and saved US$ 1.1 billion a year in production costs. In the case of Bt cotton, the reduction in the use of herbicides came to 862,000 tons, and at the same time production recorded an increase of 84,000 tons a year. In the case of varieties of Bt corn as well, there was a fall in the use of pesticides, while annual production saw an increase of 1.6 million tons.

The increase in productivity, observed in the case of corn and cotton, and the rise in the producer’s income, in the case of soybeans, can be a good alternative for developing countries. This should also contribute towards bringing closer together the curves of the growth of the world population and of grain production. According to the World Bank, the world production of grains between 1950 and 1995 accompanied the curve of population growth, while the area under cultivation remained practically unchanged (please see graph 1). Since 1985, though, it can be seen that the productivity gain remained unchanged, at around 2,500 kg per hectare, on account of the fall in the efficiency of the action of the fertilizers (see graph 2). This means that the grain/inhabitant ratio has been in decline since 1985, falling from 350 kg to 300 kg per inhabitant in 1995. In 2050, when the planet is inhabited by 9 billion persons, the hope is that science will have found a good answer for guaranteeing an efficient productionof food.

Let it be said in passing that, whatever the solution adopted for increasing food production – expanding the planted area, intensifying the use of herbicides, or adopting transgenic plants -, there will be an impact on the environment. “People forget that agriculture is one of the greatest destroyers of biodiversity. But we have to live with agriculture. The population is growing and people ought to be concerned with the development of agricultural techniques”, Reinach reckons.The doubts with regard to the production of transgenics are not exclusively a Brazilian concern. The International Council for Science (ICSU) – – analyzed 50 articles and scientific publications on GMOs published between 2000 and 2003, to ascertain the degree of consensus and the divergences of the authors over transgenics.

The conclusion was that there was consensus with regard to the safety of the transgenic foods available on the market and that, up until that moment, no evidence had been adduced as to any adverse effects arising from the consumption of these products. On the contrary: these crops are less exposed to chemical products, as they use less pesticide. The ICSU also encountered unanimity on the need for the GMOs to be studied case by case, on scientific bases, before being cultivated and taken onto the market. The divergences are related to the scope of the current methods of risk analysis and, in particular, to the use of the principle of precaution. “The precautionary approach for dealing with uncertainties calls for new technologies to demonstrate an absence of danger. As biological systems never produce certainties, zero risk is an unattainable standard”, the ICSU study observes. “The significance of laboratory studies is arguable, since it is difficult to extrapolate from the laboratory to field studies andto foresee effects of commercial use. And what constitutes an adverse environmental impact?”, the ICSU asks.

Precautionary processes are commonly used by science. Before a new product for human use is launched on the market which is the case of medicines and vaccines, for example , exhaustive tests are carried out on animals and, afterwards, on human beings, with growing samples, throughout the four stages of the experiment. But, in spite of this, the proof of absolute certainty that the medicine or the vaccine will not cause any damage to anyone, science will never be able to give. “All medicines are dangerous. They are used the risk associated with the disease to be lowered”, says Zago. The doubt that assails scientists is: what is the period for applying the precautionary principle? It would be irrational for it to be infinite. The reply to this question is crucial for science not to be paralyzed, and to guarantee the advance of research.Besides the ICSU, the Royal Society also made public a report, in February last year, presented to the British Government’s GM Science Review Panel ( gmplants), in which it concluded that the use of genetically modified plants can generate enormous benefits for farming practices, more quality in food, and bring benefits for human nutrition and health. It made a proviso that the possibility of occurrence of unforeseeable harmful alterations to the nutritional status of food is identical to those that may possibly be observed in the conventional processes for improvement. And it stressed that, up until that moment, there is no proof that GMOs cause any allergic reactions, and that this risk would be no greater than those imposed by conventional farm crops.

In another document, signed by academies of sciences of seven countries, among them the Brazilian Academy of Sciences (ABC), made public in 2000, it is claimed that genetically modified food can be more nutritive and bring benefits for the consumers, and that joint efforts ought to be made to investigate their effects on the environment. The suggestion is that the signatory countries should implant regulatory systems for identifying and monitoring adverse effects, and that private sector companies and research institutions should share genetic modification technologies that are currently covered by very restrictive agreements with patents and licenses. “There isn’t any association of scientists that declares itself in favor of allowing all and every transgenic to be used. They all recommend that a case by case analysis should be carried out”, emphasizes Hernan Chaimovich, the director of USP’s Chemistry and a member of the ABC and of the ICSU.

Basic principle of biosafety
Case by case analysis, advocated in all scientific manifestations, is a basic principle of biosafety, and it should guide the course of the researches. And, as scientific research can reduce the risks associated with the use of genetically modified products, how can one explain the population’s perplexity and doubts with regard to transgenic food Because the debate on transgenics omits the position of science on the subject, Chaimovich reckons. “The media haven’t given any room for the importance of the scientists”, he observes. “Those who appear most are the seed companies, which defend transgenics, and a few nongovernmental organizations, which attribute risks and catastrophes to biotechnology. Scientific entities have to show studies, and the media have to give space to them.”

One is also compelled to recognize that scientists have failed in their attempts to keep society informed about the progress, the risks and the advantages of the researches with GMOs. “Society needs to be much better informed, so as to take up a more balanced position with regard to something that has to do with its daily life, with the environment and with its health”, observes José Fernando Perez, FAPESP’s scientific director. “The scientific community is waking up to a responsibility from which it cannot escape. It is fundamental for there to be a communication channel for a more efficient dialog with society, making it possible for citizens to inform themselves about the potentialities and the limitations of science.”

When all is said and done – and in the light of the evidence that GMOs do not necessarily constitute a threat to human health and to the environment – the last word will lie with the consumer, since, with the rules for their production reestablished, the genetically modified products must be identified and labeled.It will not be the first time in the history of Brazil for there to be hesitation in adopting a product that is the result of the progress of science. In 1904, when the country was beginning to harmonize with the terms of the new world economic order instituted by the Scientific-Technological Revolution, in Rio de Janeiro, then the federal capital, the Brazilians rose up against the campaign for obligatory vaccination against smallpox. The campaign, decided by the presidency of the Republic, was commanded by Oswaldo Cruz, head of the General Directorate for Public Health.

In that same year, in just six months, the official records showed over 1,800 people had been hospitalized in St. Sebastian Hospital, in the Federal District, and the total of deaths had come to 4,201, according to Nicolau Sevcenko, in his book A Revolta da Vacina – Mentes Insanas em Corpos Rebeldes [The Vaccine Revolt – Unsound Minds in Rebellious Bodies]. The opposition argued that the methods for applying the decree on vaccination were truculent, the vaccines and those who applied them were hardly trustworthy, and the officials, nurses and inspectors “showed brutal instincts and dubious morality”. The government revoked the obligatory application of the anti-smallpox vaccine, and the movement ebbed. But science slowly overcame the disease.