What Will Synthetic Biology Deliver?

Suman Sahai

The behaviour of bioengineered systems remains unpredictable, a function of the fact that genetic circuits that have been created artificially tend to mutate rapidly and frequently and often become non-functional.Synthetic microorganisms should undoubtedly be treated as dangerous till proven to be otherwise.

In 2005 , scientists at the US Center for Disease Control and Prevention succeeded in synthesising the virus responsible for the Spanish Influenza , the pandemic which killed almost 100 million people between 1918 and 1919.

“Learning from gene therapy, we should imagine the worst case scenarios and protect against them” George Church, Nature, 2005

Synthetic biology is one of the new biologies. Not really a biology in the classical sense, synthetic biology is a mixture of engineering , biology , chemistry and physics which together aims to reconstruct life at the genetic level.

The era of synthetic biology has been described as an era in which significantly new gene

arrangements can be constructed and evaluated for a diverse range of applications. Craig Venter, the scientist who raced ahead of the multigovernment Human Genome Project in 2000 to crack the human genome first, is also in the forefront of the most recent breakthrough in synthetic biology. Venter’s group created a new organism, which they have termed Mycoplasma laboratorium. Starting with the bacterium Mycoplasma genitalium, the Venter group stripped the bacterium of most of its original DNA and built up a new genome using pieces of DNA synthesised in the lab. The Mycoplasma with the

largely artificial genome synthesised in the lab, has been named Mycoplasma laboratorium.

Most of the work on synthetic biology is happening in the US, with scientists at the Craig Venter Institute in Maryland taking the lead. There are other research groups also working in Europe, Japan , Israel and to some extent in India, where the National Center for Biological Science (NCBS) seems to be in the forefront. Synthetic biology is likely to expand as a discipline as more labs take up this research, specially those where genetic engineering is already established.

Although similar in many ways, there is a fundamental difference between the two disciplines. Whereas genetic engineering deals with shifting individual (natural) genes from one species to another, synthetic biology seeks to assemble new genes from bits of DNA that can be synthesised in the lab, and now increasingly, even just bought from companies selling custom made bits of DNA, called oligonuleotides.

Actually, assembling commercially available oligonucleotides to create artificial semi life forms started even before Venter’s newest achievement. In 2002, a virologist Eckard Wimmer and his research team at the University of New York, announced that they had succeeded in assembling a live, infectious polio virus from oligonucleotides bought from a commercial supplier and using as a blueprint, a map of the viral genome that they downloaded from the internet.

Going a step further, scientists at the US Center for Disease Control and Prevention managed, in a similar way, to synthesise the virus responsible for the Spanish Influenza , the pandemic which killed almost 100 million people just after World War I. Those concerned with bioterrorism, have something to worry about!

The promises of synthetic biology are many but so are its many potential risks. Synthetic biology is projected to go far ahead of genetic engineering and perform many functions

which are almost unimaginable today. Artificially constructed systems made through synthetic biology, in effect, organisms that have been constructed like Venter’s new bacterium, but far more precisely, are being projected to produce cheap drugs for malaria as also other medically useful chemicals.

Other applications are the production of industrial chemicals, cellulosic ethanol for use as a biofuel and microorganisms equipped with artificial biochemical pathways aimed to attack specific pollutants and detoxify the environment. Along with the promise of bioremediation, synthetic biology also offers more far-fetched promises like making bacterial films that can distinguish light and shade such that visual patterns can be recorded, almost like photographs. This property could have value in diagnostic tools in medicine, for detecting mineral deposits and for mapping the earth’s surface from close up.

Despite its promise and the fact that synthetic biology has grown extremely rapidly as a discipline, there are quite a few fundamental bottlenecks that still remain unresolved. One major problem is that the behaviour of bioengineered systems remains unpredictable, a function of the fact that genetic circuits that have been created artificially tend to mutate rapidly and frequently and often become non-functional. This has echoes in the phenomenon of gene silencing, encountered after genetic engineering. Silencing happens

when certain genes get switched off and stop functioning.

Drew Endy, of MIT in the US, one of the leaders in the field, has spoken often that synthetic biology will not deliver unless scientists can accurately predict how a new genetic circuit will behave once it is put into a living cell. This is the same problem as obtains in genetic engineering.

Scientists cannot predict the exact performance of a new gene once it is introduced into a living plant or animal. This explains why we see most of the problems arising, with the new genetically modified plants producing allergens and toxins. Until scientists are in a position to understand and reliably predict the molecular processes in a cell before and after intervention, the engineering of biological systems either through genetic engineering or through synthetic biology will remain ad hoc and undependable, ultimately even dangerous. It is to be hoped that the proponents of synthetic biology do not adopt the reckless path chosen by the powers that have pushed genetically engineered products prematurely onto the market , often disregarding the caution that was sounded

on safety.

With respect to potential risks, even though genetic engineering and synthetic biology are different, there is a fundamental similarity, leading to a similar approximation of risks in

both instances. In both cases, the nature and magnitude of the risk is defined by two key properties that demarcate these fields as different from those where classical risk is encountered, for instance, with hazardous waste.

One of these properties is the fact that new organisms generated either by synthetic biology or by genetic engineering are self replicating and capable of evolution. The other is that the outcome of both processes is ultimately unpredictable and so many of the risks

associated with synthetic biology (and genetic engineering) remain indefinable and unpredictable at present. The potential risks associated with synthetic biology are essentially those related to biosafety and to biosecurity.

BIOSAFETY

The risk of unintended release is as real for products made from synthetic biology as for genetic engineering but they could have graver consequences. Synthetic genomes that are entirely artificial have no genetic pedigree, so to speak. They come from nowhere recognizable and hence their properties cannot be predicted. What’s more, they could have emergent properties that could result from complex interactions between the constituent genes. The risks associated with the ‘escape’ of such organisms into natural ecosystems would be difficult to assess, nor would it be possible to foresee the kinds of damage this would unleash. The precautionary approach would dictate that synthetic microorganisms should be treated as dangerous till proven to be otherwise.

BIOTERRORISM

Scientists have found it very easy to put together DNA pieces bought from commercial suppliers and reconstitute the polio virus and the Spanish flu virus. There is reason to be concerned in these times of terrorism, that bioterrorists can add more deadly weapons to their arsenal in the form of virulent new organisms, particularly of a kind not known to humans and against which humans would have no immunological defence. Sophisticated scientific laboratories exist in many places which feed terror and it is not unthinkable that

such laboratories could produce novel microorganisms and infectious agents using the sophisticated tools of the new biologies. The threat of bioterrorism certainly increases with the development of technologies like synthetic biology. Introducing and implementing regulatory control is a challenge that governments will have to think about but a realistic appraisal would indicate that this is almost certainly impossible to enforce. The scenario of dangerous microorganisms in the ‘wrong’ hands is all too real and in my view, out of the possibility of control. Scientists must do serious introspection to see whether this research should continue.

US Forces Changes In India's GM Policy

Suman Sahai

The Government of India had issued a notification on August 23,2007,which came into effect on September 11,2007,withdrawing all existing regulatory oversight over the import of GE foods. Now, GE foods can be imported without having to take any permission from regulatory agencies, as has been the case so far. The new notification exempts importing agencies from even informing the government.

Gene Campaign filed a writ petition in the Supreme Court challenging the notification issued by the government. It appealed to the Court to strike down the notification since it is "unconstitutional, being violative of Articles 14 and 21 of the Constitution"; it had further requested the Court to strike down the new provisions since these give uncanalised power to the government which power is likely to be abused and is therefore

violative of Article 14 of the Constitution.

The Supreme Court heard the matter on November 19 and issued a notice to the Government of India. The Court issued a further notice on Gene Campaign's application that a stay be granted on the notification till the issue is finally decided. This means that the government has been put on alert that the Supreme Court was now watching the deregulation of GM foods.

Until now, in view of the known health risks associated with GE foods, government guidelines required that import of GE foods can only take place with the express permission of the apex regulatory body in India, the GEAC (Genetic Engineering Approval Committee).Further, any handling of GM foods was to be done only after these were labelled as such.

The regulatory oversight that existed prior to the new notification was necessary and appropriate since it had allowed India to monitor the entry of food products produced by a new technology that is known to produce toxic and allergic compounds. It also allowed India to maintain vigil that food products rejected by other countries in Europe, Africa and Middle East are not in fact being dumped on us. The arbitrary withdrawal of the regulatory oversight without any scientific reason and without any consultation with a range of stakeholders that are engaged with GE technology and policies associated with it, is a dangerous development. It will benefit the producers and exporters of GM foods, like the US, and pose health dangers to the Indian population.

The move is all the more inexplicable, at a time when scientific evidence is mounting from laboratory tests in various parts of the world, that GE foods can in fact cause serious damage to health. Confronted with this scientific data, we need to upgrade our food testing systems and make them more stringent and comprehensive, not dismantle them, as the government is doing. It is incomprehensible that instead of strengthening our systems to ensure that foods which have the potential to damage health do not reach the market, the government has decided to withdraw all opportunities to test and regulate such novel and controversial foods.

It is also a matter of considerable concern that unfettered access to unknown foodstuffs is being allowed in the absence of a legal regime for liability and redress. India has still not introduced a law on liability for this sector, even though it is required to do so by the Cartagena Protocol on Biosafety. This means there is no law in the country that can fix responsibility and claim compensation if something should go wrong with the environment or with animal and human health, from the cultivation and consumption of GE crops and foods.

The new notification of the Ministry of Environment and Forests will in effect provide unrestricted entry to untested foods of dubious origins, especially since the imported GM food does not have to be labelled. This denies consumers the right to exercise free choice in the matter of the food they wish to eat. This is in violation of the Consumer Protection Act that grants consumers the right of informed choice.

The government's notification also goes against India's commitment to mandatory labelling of GE foods, a position the Indian delegation has consistently maintained in international negotiations, particularly at the WHO-FAO led Codex Committee on Food Labelling. Both the dilution of India's position on mandatory labelling and the curious deregulation of the GM food sector appear to be the result of increasing American interference in Indian policy. The move to deregulate the GM crops and foods sector appears to be linked to the Indo-US deal on Agriculture. It is truly ironic that the future of the Indo-US nuclear deal, the reason why India gave concessions in the agriculture sector, is uncertain, but the agriculture deal is moving ahead, securing gains for the US GM industry at the cost of public health in India

Novartis Shown Its Place

Suman Sahai

In one of the first challenges posed to the Indian courts on the award of patents in the pharmaceutical sector, it is heartening to note that judges of the Chennai High Court have spoken in favour of the Indian people and their right to affordable health care. The case

refers to the patent filed by the Swiss drug multinational Novartis in 1998,for its cancer drug Glivec. Under the mailbox provision provided during the transition from the Uruguay GATT round at the end of 1994 and the time that countries amended their patent acts to introduce both process and product patents, Novartis had enjoyed several years of Exclusive Marketing Rights (EMR)on Glivec.

The Chennai Patent Office rejected the Novartis ’ application in 2006 on the grounds that it was not innovative enough. The patent office said that the new claim was for different forms of the same drug (salt and crystalline)and did not involve any inventive steps,

hence did not merit a patent. In order to block the efforts of pharma giants to ‘evergreen ’ their patents by extending the patent period by introducing frivolous changes, the Indian Patent Act has incorporated a provision under Section 3(d)according to which slight

variations of the original product are not patentable unless there is a significant difference in the efficacy of the drug as a result of the small change. This was not the case with the Novartis drug.

On being denied the patent, Novartis took the unprecedented step of moving the Chennai High Court against the order of the Chennai Patent Office.If this was not brazen enough, it challenged the validity of the Indian Patent Act itself, saying that it was not compliant

with WTO/TRIPS. Then it went one step further and challenged the constitutionality of Section 3(d),further accused India of not meeting the ‘agreed ’ deadline to become compliant with TRIPS (Trade Related Intellectual Property Rights),that is,not changing its Patent Act early enough. After this, for good measure, Novartis came up with another bald faced idea and challenged the appointment of Sri C Chandrashekhar to the Indian Patent Appellate Board (IPAB),accusing him of being biased and suggesting his decisions would be unfair. And if all this was not brazen enough, Novartis began to issue threats that it would move its business out of India and deny India life-saving drugs because of its actions in not acceding to all of Novartis ’s indefensible claims.

The Novartis example is a good test case since it offered up almost the entire repertoire of threats and intimidations that corporations are known to indulge in to get their way with developing country governments. In this case, Novartis had no hesitation in breaching the (sometimes thinly held)limits normally maintained by outside agencies that must steer very clear of interfering in the affairs of a sovereign nation.

It is to the credit of the Chennai Bench that heard the Novartis case which instead of being persuaded by the aggressive onslaught,as has sometimes been witnessed in the past, they stood up clearly on the side of justice and the side of the poor.Not only did they uphold the appointment of Sri Chandrashekhar, Justices R Balasubramanian and Prabha Sridevan summarily rejected the audacious challenge made by Novartis and told the company to seek relief in the WTO dispute process for its complaints about India ’s compliance or lack of it with the WTO provisions. The Bench also dismissed the attempts to interfere in India ’s Patent Act (with reference to Section 3(d),stating that the Indian law was the law of a sovereign nation; it was in consonance with the country ’s constitutional obligations and invoking Section 3(d)to restrict the ever greening of patents to achieve the goals of justice.

I would add a final chapter to the Novartis saga. That is to issue the threat of banning products made by Novartis so that a message goes out to other corporations who have such intimidating tactics in mind. Many years ago ,when I was a researcher at the Human Genetics Institute in Heidelberg, an issue came up about enforcing the patent on a very basic technique used in all genetics labs, the Polymerase Chain Reaction (PCR). The patent on PCR was held by another Swiss multinational called Hoffman La Roche which was also a pharmaceutical company. Enforcing their patent on the use of PCR would mean that no genetics research could be conducted without paying royalties to Hoffman La Roche.The genetics research institutions in Heidelberg took a decision that if Hoffman La Roche actually enforced their patent and tried to extract royalties from every genetics lab, the university hospitals would retaliate by banning drugs produced by the company. The message must have been conveyed. Roche never enforced the PCR patent!

Novartis Shown Its Place

Suman Sahai

In one of the first challenges posed to the Indian courts on the award of patents in the pharmaceutical sector, it is heartening to note that judges of the Chennai High Court have spoken in favour of the Indian people and their right to affordable health care. The case

refers to the patent filed by the Swiss drug multinational Novartis in 1998,for its cancer drug Glivec. Under the mailbox provision provided during the transition from the Uruguay GATT round at the end of 1994 and the time that countries amended their patent acts to introduce both process and product patents, Novartis had enjoyed several years of Exclusive Marketing Rights (EMR)on Glivec.

The Chennai Patent Office rejected the Novartis ’ application in 2006 on the grounds that it was not innovative enough. The patent office said that the new claim was for different forms of the same drug (salt and crystalline)and did not involve any inventive steps,

hence did not merit a patent. In order to block the efforts of pharma giants to ‘evergreen ’ their patents by extending the patent period by introducing frivolous changes, the Indian Patent Act has incorporated a provision under Section 3(d)according to which slight

variations of the original product are not patentable unless there is a significant difference in the efficacy of the drug as a result of the small change. This was not the case with the Novartis drug.

On being denied the patent, Novartis took the unprecedented step of moving the Chennai High Court against the order of the Chennai Patent Office.If this was not brazen enough, it challenged the validity of the Indian Patent Act itself, saying that it was not compliant

with WTO/TRIPS. Then it went one step further and challenged the constitutionality of Section 3(d),further accused India of not meeting the ‘agreed ’ deadline to become compliant with TRIPS (Trade Related Intellectual Property Rights),that is,not changing its Patent Act early enough. After this, for good measure, Novartis came up with another bald faced idea and challenged the appointment of Sri C Chandrashekhar to the Indian Patent Appellate Board (IPAB),accusing him of being biased and suggesting his decisions would be unfair. And if all this was not brazen enough, Novartis began to issue threats that it would move its business out of India and deny India life-saving drugs because of its actions in not acceding to all of Novartis ’s indefensible claims.

The Novartis example is a good test case since it offered up almost the entire repertoire of threats and intimidations that corporations are known to indulge in to get their way with developing country governments. In this case, Novartis had no hesitation in breaching the (sometimes thinly held)limits normally maintained by outside agencies that must steer very clear of interfering in the affairs of a sovereign nation.

It is to the credit of the Chennai Bench that heard the Novartis case which instead of being persuaded by the aggressive onslaught,as has sometimes been witnessed in the past, they stood up clearly on the side of justice and the side of the poor.Not only did they uphold the appointment of Sri Chandrashekhar, Justices R Balasubramanian and Prabha Sridevan summarily rejected the audacious challenge made by Novartis and told the company to seek relief in the WTO dispute process for its complaints about India ’s compliance or lack of it with the WTO provisions. The Bench also dismissed the attempts to interfere in India ’s Patent Act (with reference to Section 3(d),stating that the Indian law was the law of a sovereign nation; it was in consonance with the country ’s constitutional obligations and invoking Section 3(d)to restrict the ever greening of patents to achieve the goals of justice.

I would add a final chapter to the Novartis saga. That is to issue the threat of banning products made by Novartis so that a message goes out to other corporations who have such intimidating tactics in mind. Many years ago ,when I was a researcher at the Human Genetics Institute in Heidelberg, an issue came up about enforcing the patent on a very basic technique used in all genetics labs, the Polymerase Chain Reaction (PCR). The patent on PCR was held by another Swiss multinational called Hoffman La Roche which was also a pharmaceutical company. Enforcing their patent on the use of PCR would mean that no genetics research could be conducted without paying royalties to Hoffman La Roche.The genetics research institutions in Heidelberg took a decision that if Hoffman La Roche actually enforced their patent and tried to extract royalties from every genetics lab, the university hospitals would retaliate by banning drugs produced by the company. The message must have been conveyed. Roche never enforced the PCR patent!

PATENTS Inventiveness Redefined

Suman Sahai

The recent landmark judgment by the US Supreme Court in KSR vs. Teleflex case, has come at the right time to take care of the incessant granting of patents. The court has sought to redefine inventiveness/obviousness which is one of the core issues of patenting.

Invention as a human activity is much older than the concept of intellectual property. Of late, the concept of “inventiveness ” has come under much discussion with the rate at which patents are being granted all over the world.

Inventiveness in simple terms is defined as the power of creative imagination while a more technical definition for inventiveness would be its not being obvious to a person skilled in the technological field of the invention at the time an invention is made.

Scientists and legal experts have been racking their brains to define this term while granting patents. But often the nuances are ignored through oversight which results in turning out patents which are legally incorrect and which serve to override the efforts and utility of the pre-existing patents.Such has been the case in the US where US Patents and Trademarks Office (USPTO) has been granting patents incessantly till it decided to put a stop to this process. The rapid increase in patenting in the last decade or so is also indicative of a shift in how organisations do research.

The recent landmark judgement by the US Supreme Court in KSR vs. Teleflex case, has

come at the right time to take care of the situation in a bid to redefine inventiveness/obviousness which is one of the core issues of patenting.

This patent case involves computerised adjustable gas pedals instead of a manual pedal.In a conventional automobile, a driver presses the gas pedal to control the quantity of fuel to be delivered to the engine while in the new one there is a computerised pedal for controlling fuel supply to the engine of an automobile.

This advancement first of all is incremental and the type of pedal is apparently no new invention as it points to the same use of a known art. The courts in the US have held for many years that the requirement of inventiveness is not satisfied if there is no change in the respective functions.

Defining obviousness

In its recent decision in KSR v. Teleflex ,the US Supreme Court unanimously rejected the rigid application of the previous "teaching, suggestion, motivation "test (TSM test as used in Graham ’s case, see box)and has clarified confusions prevailing in regard to non-obviousness of an invention with new inputs to look at this issue. The US Supreme Court said that when a court transforms the general principle into a rigid rule (for eg, TSM rule),it limits the obviousness inquiry. A vested interest in patent law and the ease of obtaining patents are at the centre of the case.

The requirement for inventiveness was already there in the patent laws created in the US in 1952.The law states that a patent shall not be granted if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which the subject matter pertains.

The US codified the “obviousness ” test for patentability in 1952 but unfortunately it did

not provide any specific guidelines as to what its meaning was. It was left to the courts to interpret the idea. Since then, the attempts have been quite experimental with different tests over the years, ranging from the requirement that a patentable invention must result from one ’s innate imagination to the more recent Court of Appeals for the Federal Circuit (CAFC)test of ‘teaching, suggestion, or motivation ’ (TSM).

The US Supreme Court has made it clear that the courts must ask whether the improvement is more than the known use of prior art elements according to their established functions. Some of the more important statements of the US Supreme Court in the KSR v. Teleflex case are that:

• An ordinary person has also common sense and creativity to understand the underlying scientific principles.
• The court can look at interelated teachings, market forces, common knowledge skill and creativity of a person of ordinary skill before taking a decision on inventiveness
• in a patent.
• Obviousness can be shown by any need or problem known in the field which provides a reason to combine known elements in the prior art;
• Obvious uses of familiar items, beyond their primary purpose, may be fit together by a person of ordinary skill like pieces of a puzzle, and such a person is not limited only to the primary uses of these items;
• A patent claim can be obvious if the combination of elements was obvious and easy to try; and,
• The combination of old elements with no change in their respective functions according to known methods is likely obvious when it does no more than yield predictable results.
• The new policy rather seems to emphasise that “ordinary innovation ” is not entitled to a patent..

Conclusion

The message conveyed to the outside world through this US court decision is that patents for mere increment tal improvements are to be denied or invalidated. Patents that involve real innovation, cutting-edge ideas, have a spark of genius and pass the possibly strict scrutiny of the patent offices and the courts will only be entitled for patenting.

The decision by the patent offices on raising the standards of inventiveness is a welcome move as it will serve as a lesson for the developing countries. A case in point is the recent move by the Chennai High Court in India which denied the patent over the cancer drug Glivec filed by pharma giant Novartis ’ on the ground of obviousness.. The modification in the new drug was deemed as just an incremental advancement over the pre-existing elements. Though this case is still going on,the verdict so far is laudable in the sense that pharmaceutical companies in order to maintain their competitive advantage in the market would now have to redefine their concept of inventiveness within the purview of the legal status

of patenting.

The other impact of this decision is that there will be less cases of infringement of patents and consequently less appeals.This development at the least calls for a clearer mandate on the legal status of patents.

Nevertheless,this redefining of inventiveness no doubt raises a number of questions.These include:

• Will patents become less or more valuable because of this decision?

• What exactly is a “real innovation ” that should be patentable?
• If only unpredictable development is to be patented how would one know that it was unpredictable?
• Will patent examiners now find more inventions obvious, or refuse the patent, withhold the patents?
• Will more appeals have to be filed?
• What effect will all this development have on the cost and time involved in filing patents?
• Will this make patenting more competitive?

These questions will only be answered on a case-to- case basis with the passage of time.

THE GRAHAM FACTORS

A notable case in the US patent history was the Supreme Court’s attempt to determine obviousness and nonobviousness in Graham et al v. John Deere Co. of Kansas City et al, (1966). These are commonly referred to as the "Graham factors". The court held that obviousness should be determined by looking at the following three things.

• the scope and content of the prior art;
• objective evidence of nonobviousness; and
• the differences between the claimed invention and the prior art. Along with these, the court outlined examples of factors that show "objective evidence of non-obviousness". They are:
• commercial success in the market; long-felt but unsolved needs; and
• failure of others to solve a particular field.

EPO'S PROBLEM-SOLUTION APPROACH

The basic assumption of the European Patents Office is that every invention is a solution to a technical problem and this promotes the view that the inventive step corresponds to the step from the problem to the solution. The Problem-Solution Approach method comprises of three basic stages.

PRIOR ART

The most relevant and the closest prior art in that particular case had to be defined. Consequent to this, a thorough comparison has to be made between what is being claimed and what is there in the prior art. The differences between the matter claimed and the subject matter in the prior art is very important in deciding the obviousness state of the concerned invention.

THE OBJECTIVE PROBLEM

The identification of a real problem is another major aim. Then, whether the claimed invention solves the problem or not is another major task.

IS THE INVENTION OBVIOUS?

In the last stage, an assessment is made on the basis of existing differences between the most relevant prior art and the invention claimed, that whether the prior art offers a solution to the problem identified in the second invention.

Biofuel vs. Food Security

Suman Sahai

The natural question arising from the diversion of arable land to bio-energy crops is what impact is this likely to have on food production and food security

Not to be left behind in the current global craze about biofuels, India has begun biofuel programmes and is in the process of preparing a policy aimed at accelerating the development of the sector. The proposed policy will cover research and development, capacity building, setting up a minimum support price for Jatropha and other non-edible oilseeds, norms for purchases and registration for enabling biofuel use. The plan is to start with a blending proportion of 5 per cent (5 per cent biofuel with 95 per cent petroleum) by 2012, 10 per cent by 2017 and over 10 per cent after 2017.

The research focus is to improve oil content of oil seeds, increase crop yields, and reduce the environmental impact of biofuels’ use. The first is significant because the Jatropha species being used in India, Jatropha curcas, is low yielding, giving one tonne of seeds per hectare under optimal conditions.

With a seed price of Rs 5 per kg, the farmer would make only Rs 5,000 per hectare per year. This makes it a loss making venture. In any case, the overall desirability and economics of biofuel has been questioned by Mark Anslow in a recent issue of the Ecologist. Pimentel and Patzek of Berkley have done research that shows that biofuels give out less energy when burnt than was used in their manufacture.

According to them, 6,597 kilocalories of non-renewable energy are required to produce a litre of ethanol from corn, which contains only 5,130 kilocalories of energy, which is a 22 per cent deficit.

On top of this, biofuels are more expensive that petrol. In the US, a litre of petrol costs roughly 33 cents to produce; a litre of ethanol can cost up to $1.88. At present, this difference is covered by subsidies. Germany subsidises biofuels to the value of 47 cents per litre, and France to the value of 33 cents per litre. If these subsidies were to be removed, would biofuels become competitive? And at this pricing, would biofuels be an energy efficient option for developing countries that cannot offer equally high subsidies? And will this really make a dent in the use of petroleumbased fuels?

A research study published by the OECD (Organisation for Economic Cooperation and Development) shows that more than 70 per cent of Europe’s farmland would be required for biofuel crops to account for even 10 per cent of road transport fuel! Other figures suggest that even if high yield bio-energy crops were grown on all the arable land on earth, the biofuel produced would cater to only 20 per cent of current demand.

Opening the door to GE crops?

Many commentators are of the view that the biotech lobby is using the alleged environmental bonus of cropbased agro-fuels to push the case of genetically engineered (GE) crops which are fiercely resisted as food in many parts of the world.

The leading biotechnology corporation Syngenta has applied for permission to import GE maize into Europe for processing into fuel. The particular GE maize has been engineered to express an enzyme that shortens the time it takes to ferment the feedstock into alcohol. The companies are developing a GE cassava to produce agro-fuel and large amounts of GE corn in the US are being cultivated as agro-fuel feedstock.

The genetic engineering industry is keen to use acceptance of biofuel as a strategy to speed up acceptance of GE crops in Africa, and the industry is working on a number of GM biofuel crops tailored for African conditions. Many African nations are opposed to GE crops and most have not yet developed biosafety policies. The industry is trying to push with what they think will be more acceptable energy crops rather than food crops, to prompt policy making that would open the door to other GE crops in the future.

Impact on food prices

The natural question arising from the diversion of arable land from food production to bio-energy crops, is what impact is this likely to have on food production and food security. Biofuel proponents, and there is already a vocal ‘biofuel lobby’, argue that bio-energy crops would only be grown on degraded or wasteland, not fertile land.

COMPARING THE BIOFUEL AGENDAS
INDIA	EU	BRAZIL	THAILAND	CANADA
Substitution of 10% of oil requirements by 2032	By 2020, 10% of transport fuel used will be green	Biodiesel will make for 5% by 2013	Biofuel to meet 2% of its total energy needs by 2010	By 2010, 45% automotive fuel sold will 10% doping

But, if the wasteland is capable of supporting Jatropha cultivation, should it not be used for the cultivation of selected cereal or oil crops, or if not that, then fodder grasses? India and all of South Asia have large livestock populations, which serve as additional support for local food security. The region is deficient in fodder and all kinds of non-arable land should be diverted to fodder grasses, not crops to produce agrofuels.

The agro-fuel story shows up another dimension: the hypocrisy of the biotech lobby that does not tire of making the point that GE crops are necessary to produce more food for the growing world population, which according to them, cannot be fed from existing crop varieties. They make the case that relying on non-GE crop varieties would create food deficits and lead to forests being cleared for cultivation, to meet the burgeoning food demand. Yet the same companies think nothing of diverting limited agricultural land to produce crops, not to support food security, but to produce agro-fuel.

Critics fear that the growth of the agro-fuel sector will be detrimental to food production. The impact on food prices of diverting food crops to ethanol production is already becoming visible. Pork prices in China have begun to rise as a result of rising costs of animal feed consisting principally of corn and soybean, both crops that the US is diverting to its biofuel programmes. Less US corn and soybean on the market means higher prices for animal feed and so higher prices for meat. Beijing is slowing down China’s ethanol production drive after increase in corn prices world wide prompted concern about inflation and food security at home. China is the world’s number-three ethanol producer, after the US and Brazil, manufacturing 1.2 million tonnes of ethanol from corn and wheat feedstock. Chinese officials are waking up to the fact that they will not be able to produce enough corn to supply domestic food needs and support a biofuel programme. These officials realise that they cannot buy enough corn from the world market either, with the US, the world’s largest corn supplier, hoarding its corn and soybean for its own ethanol programme.

Warning signals about the consequences of the USled biofuel fad on food and feed availability are being sent by the FAO. A report prepared by the World Food Organization and the OECD predicts that the current trend will take land out of food production and increase the price of commodities such as sugar, maize and palm oils.

The report anticipates that this will lead to a rise in food prices over the next ten years. While higher food prices will be profitable for food exporting countries and large farmers, they will threaten the economies of food importing countries, the livelihoods of their farmers as well as the food available to the urban poor in these countries.

The global rush to switch from oil to energy derived from plants is being led by the rich countries who want to see energy plants grown extensively for fuel as a way to reduce their own climate changing emissions. The UN is urging governments to beware the human and environmental consequences of the agro-fuel trend, some of which could be irreversible. They warn that taking the current agro-fuel route will lead to deforestation, push small farmers off the land, and lead to serious food shortages and increased poverty. India should review its biofuel policy and examine our natural advantages to see what kinds of strategies are viable for producing supplementary energy.

New Research Rocks Base of Agbiotech

Suman Sahai

A paper published in June 2007 by a consortium of scientists from 80 research organisations has provided evidence that genes do not necessarily behave in a linear fashion with information flowing one way, from DNA to RNA to protein, as was thought till now. This central dogma that has been the bedrock of genetics and the foundation on which the genetic engineering industry is based, has been challenged by a growing collection of data but scientists have been reluctant to revise the scientific principles established by the Watson-Crick discovery of the structure of DNA and the subsequent understanding of gene function.

Now, unequivocal evidence comes from research organised by the US National Human Genome Research Institute, which has found that the human genome is not really a clear and organised set of genes but rather a tangle of overlapping, interacting genetic material that functions as a complex network, with highly nuanced gene regulation. Almost none of these mechanisms are understood. Not being able to predict how genes will behave strikes at the very basis of using genetic engineering as a tool to create new products. The biotechnology industry is built on the linear model of the “one gene, one protein” principle, postulated by scientists who created recombinant DNA in the 1970s. Earlier, it was thought that genes had clearly defined functions, therefore a gene from any organism could fit neatly and predictably into any other organism, however unrelated, and carry on its prescribed business. In this way, the Bt gene that produces a toxin in a soil bacterium is presumed to perform exactly the same function when inserted into cotton, or rice plants.

The new research shows that this assumption cannot be upheld. The use of genetic engineering to create new products rests on the presumption that there is a universal, genetic code that sets the rules for creating proteins from DNA and that the rules are virtually identical across all organisms. Even before this research on the human genome, the theory of a uniform system for making new proteins was challenged by a number of

scientific discoveries like the presence of large amounts of ‘junk DNA’ in all organisms and the fact that the highly complex human organism was found to have just 30,000 genes, a fairly small number considering the myriad functions a human being performs.

The new research casts the spotlight on the role of ‘junk DNA’, the large amounts of DNA detected during genome sequencing for which no clear functions can be ascribed. It is now accepted that the so-called “junk” DNA has a key regulatory role and it is of critical importance in regulating gene expression in organisms, a process about which there is as yet little understanding.

Apart from the new evidence and the presence of junk DNA, there are other findings that challenge the one gene-one protein foundation of agricultural biotechnology. One of these is the discovery that DNA is not the sole hereditary material and not the only means of transmitting information for new protein synthesis.

Understanding of the Mad Cow Disease and its link with the human Jakob-Creutzfeldt disease shows that both diseases can be passed from generation to generation not via genes, but via a protein molecule called a ‘prion’. Pioneering work done in the US by Stanley Prusiner, Susan Lindquist and Eric Kandel indicates that prions mediate a form of protein-based information flow, which seems to be important in a variety of biological processes. To all this, if we add what is being discovered about the other ways in which RNA acts and the process of RNA interference, the reliability of genetic engineering becomes questionable. RNA’s normal role is to carry a message from the DNA to the cytoplasm where it provides the direction for making proteins. Now it appears that ordinary RNA can enter a cell, seek out a gene’s protein making template and then destroy it. This process is called RNA interference.

A complex, interactive network of genetic material incorporating so-called ‘junk DNA’, prions as units of heredity and the phenomenon of RNA interference, invalidates the premise on which agricultural (and other) biotechnology has been founded. Evidence that gene expression is complex and non-linear begins to explain why so many things go wrong during the process of genetic engineering and why predicting its outcome remains a gamble. This opens up the question about the extent to which genetic engineering can be considered accurate and predictable as a ‘manufacturing process’. What else is transmitted along with genes and how do these factors determine the outcome? How do genes actually function in the new environment and can one ever hope to control the complex regulatory mechanisms that come into play once a gene, or many genes, are engineered into another background?

Regulate Cord Blood Banks

Suman Sahai

India is emerging as one of the leading centres for cord blood banks, which can provide stem cells for regenerative medicine. These are essentially blood banks, which collect, process and store umbilical cord blood for transplants. Umbilical cord blood is blood from the placenta and is rich in stem cells. Cord blood is collected after the umbilical cord has been detached from the newborn, and utilised as a source of stem cells for transplantation. Umbilical cord blood is playing an increasingly important role in the treatment of leukemia and other life-threatening diseases. More easily accessed than embryonic stem cells and more flexible than adult stem cells, the stem cells recovered from the blood in the umbilical cord provide a non-controversial treatment option for a range of diseases.

India opened its first cord blood bank in Chennai in 2004, with a drive to collect and store umbilical cord blood in a private bank. Twelve pregnant women registered with the private bank called Life Cell to store their baby’s umbilical cord blood. LifeCell guarantees that the stem cells gained from the cord blood will be stored for 21 years at a cost ranging from Rs 30,000 to Rs 60,000. Since then, several other cord blood banks have come up in India, many with international collaboration, all with similar price tags. Large private banks like Life Cell, TIFR (Tata Institute of Fundamental Research) and Cryostem Karnataka Pvt Ltd are entering the international market and will bid for international funds to conduct research on embryonal stem cells. All three are recognised by the National Institute of Health (NIH) in the US, which paves the way for their international operations.

India is seen a desirable destination for setting up cord blood banks because of its large, young population of ethnically and genetically diverse potential donors. The use of stem cell therapy in a number of life threatening diseases promises to be a money spinner in the medical sector. The cord blood storage market is currently estimated to be about US$2 billion, with every prospect of substantial growth in the coming years. As in all other fields of medical treatment, the question here is also that of regulation and equitable use. So far, the only countries that have put in place regulations for stem cell research and development, are the US, China, Singapore, Israel, Belgium and UK.

India has prepared some guidelines but these are not official yet. Broadly, these guidelines allow work on cord blood, adult and embryonic stem cells but prohibit the use of adult stem cells to create a new zygote, in other words, a new embryo. A nodal body, the National Apex Committee for Stem Cell Research and Therapy, has been proposed where all researchers and institutions working on stem cells will have to register. Permission from this body will be required for all applications of stem cells, including research. All stem cell lines that have been established, along with the source of the original material, will also have to be registered with the apex body. Given its potential for use and abuse, a regulatory system governing the use of cord blood stem cells will have to be vigilant in ensuring that not just private players but also public banks are set up for cord blood, which can be accessed by the public.

New technologies cannot be such that they shut out the poor because they are expensive and unaffordable. Even with stringent regulations, there are outstanding ethical and practical dilemmas associated with this promising but radical technology. At the simplest level, is the question of the facilities themselves: how reliable is the infrastructure for reliable and safe storage; what will be the accepted methodologies of processing and transport of such materials; and, how will the integrity of the stem cells be ensured. There is no law yet, for instance, to govern ownership of tissues like the umbilical cord or the stem cell line generated from the cord blood. What kind of intellectual property regime will we allow on aterial, which belongs to individuals but has been processed by researchers and institutions? What kind of liability laws will govern this field if things go wrong and accidents happen? How will awareness be created among the public about the availability of this facility, so that its use does not remain restricted to only those who can afford private cord blood banks. Necessary policy will need to be formulated to ensure a sufficient number of public cord blood banks and investment must be made to ensure that the public, specially the poor, can also bring their babies for cord blood storage in the hope of treating future diseases.

Regulate Cord Blood Banks

Suman Sahai

India is emerging as one of the leading centres for cord blood banks, which can provide stem cells for regenerative medicine. These are essentially blood banks, which collect, process and store umbilical cord blood for transplants. Umbilical cord blood is blood from the placenta and is rich in stem cells. Cord blood is collected after the umbilical cord has been detached from the newborn, and utilised as a source of stem cells for transplantation. Umbilical cord blood is playing an increasingly important role in the treatment of leukemia and other life-threatening diseases. More easily accessed than embryonic stem cells and more flexible than adult stem cells, the stem cells recovered from the blood in the umbilical cord provide a non-controversial treatment option for a range of diseases.

India opened its first cord blood bank in Chennai in 2004, with a drive to collect and store umbilical cord blood in a private bank. Twelve pregnant women registered with the private bank called Life Cell to store their baby’s umbilical cord blood. LifeCell guarantees that the stem cells gained from the cord blood will be stored for 21 years at a cost ranging from Rs 30,000 to Rs 60,000. Since then, several other cord blood banks have come up in India, many with international collaboration, all with similar price tags. Large private banks like Life Cell, TIFR (Tata Institute of Fundamental Research) and Cryostem Karnataka Pvt Ltd are entering the international market and will bid for international funds to conduct research on embryonal stem cells. All three are recognised by the National Institute of Health (NIH) in the US, which paves the way for their international operations.

India is seen a desirable destination for setting up cord blood banks because of its large, young population of ethnically and genetically diverse potential donors. The use of stem cell therapy in a number of life threatening diseases promises to be a money spinner in the medical sector. The cord blood storage market is currently estimated to be about US$2 billion, with every prospect of substantial growth in the coming years. As in all other fields of medical treatment, the question here is also that of regulation and equitable use. So far, the only countries that have put in place regulations for stem cell research and development, are the US, China, Singapore, Israel, Belgium and UK.

India has prepared some guidelines but these are not official yet. Broadly, these guidelines allow work on cord blood, adult and embryonic stem cells but prohibit the use of adult stem cells to create a new zygote, in other words, a new embryo. A nodal body, the National Apex Committee for Stem Cell Research and Therapy, has been proposed where all researchers and institutions working on stem cells will have to register. Permission from this body will be required for all applications of stem cells, including research. All stem cell lines that have been established, along with the source of the original material, will also have to be registered with the apex body. Given its potential for use and abuse, a regulatory system governing the use of cord blood stem cells will have to be vigilant in ensuring that not just private players but also public banks are set up for cord blood, which can be accessed by the public.

New technologies cannot be such that they shut out the poor because they are expensive and unaffordable. Even with stringent regulations, there are outstanding ethical and practical dilemmas associated with this promising but radical technology. At the simplest level, is the question of the facilities themselves: how reliable is the infrastructure for reliable and safe storage; what will be the accepted methodologies of processing and transport of such materials; and, how will the integrity of the stem cells be ensured. There is no law yet, for instance, to govern ownership of tissues like the umbilical cord or the stem cell line generated from the cord blood. What kind of intellectual property regime will we allow on aterial, which belongs to individuals but has been processed by researchers and institutions? What kind of liability laws will govern this field if things go wrong and accidents happen? How will awareness be created among the public about the availability of this facility, so that its use does not remain restricted to only those who can afford private cord blood banks. Necessary policy will need to be formulated to ensure a sufficient number of public cord blood banks and investment must be made to ensure that the public, specially the poor, can also bring their babies for cord blood storage in the hope of treating future diseases.

Agricultural Biotechnology Growing, Unregulated

Suman Sahai

The government admits that the regulatory framework is not in consonance with biosafety requirements and the way that biotechnology is being adopted in India, yet , policies andregulatory structures have not changed.

There is no national policy on biotechnology in India to guide the adoption of genetically engineered products. Research and product development is proceeding rapidly in both agriculture and pharmaceuticals in the absence of a guiding policy document. Despite demands from several official and non-official quarters, a national policy for biotechnology has yet to be developed. The legislative framework on agro-biotechnol-ogy is provided under the Environment (Protection) Act. The Rules for the Manufacture, Use/Import/Export and Storage of Hazardous Micro Organisms/Genetically Modified Organisms or Cells formulated under the Environment (Protection) Act provides for a multi-tiered regulatory framework.

The procedures under the Rules for the Manufacture, Use/Import/Export and Storage of Hazardous Micro Organisms/Genetically Modified Organisms or Cells, are lengthy and inadequate regarding biosafety. The govern-ment admits that the regulatory framework is not in consonance with biosafety requirements and the way that biotechnology is being adopted, yet, policies and regula-tory structures have not changed.

Bowing to public demand for better and more trans-parent governance, the government finally constituted two task forces on biotechnology, one to make recom-mendations in agriculture, chaired by Dr MS Swaminathan; the other to make recommendations for streamlining the regulatory framework for recombinant pharma, chaired by Dr RA Mashelkar. The mandate was to formulate a long-term policy on applications of biotechnology in agriculture and pharmaceuticals, and suggest modifications in existing administrative and procedural arrangements. Both task forces have found the regulatory system to be cumbersome, ambiguous and inadequate to deal with the challenges of transgenic technology in agriculture as well as pharmaceuticals. Their recommendations have not yet been acted upon.

The lack of transparency in the execution of agbiotechnology has frustrated civil society organizations for a number of years. The government does not provide any information on transgenic research, field trials or biosafety, despite persistent enquiries. There is neither interface with the public nor any consultations with it. Only after the passage of the Right to Information ( RTI) Act, has it become possible at least for some groups to try to access information. Most often, however relevant information is not provided or it is denied outright under the clause of ‘confidential business information’. Organisations like Gene Campaign and Greenpeace are in the forefront of trying to loosen up the provisions of the RTI Act by contesting and challenging the government’s responses. Progress is slow so far An Expert Committee was constituted in 2004 to frame a National Policy on Biotechnology. The constitution of this Committee and the process it adopted has been widely criticised as unrepresentative and non-trans-parent.

The foremost critic has been this writer (a member of the Expert Committee) who has spoken out against the absence of any consultative process and the presentation of a draft report of which the authorship is unknown. No further consultation has taken place on the draft National Biotechnology Policy, nor is the further course of action known with regard to this document.

The government has not yet implemented a policy for segregation, traceability and labelling of GE crops and foods, although large-scale field trials for brinjal, rice and okra are being conducted as a prelude to commercial cultivation. A number of food imports have been allowed under open

license and several processed foods are being imported, particularly from the US and SE Asia, which could contain GE ingredients. There is no mechanism to regulate imports nor is there a policy for labeling these products. Traders have no idea about GE crops and foods, what labelling is and how or why it should be done. There is very poor aware-ness about the nature of genetic engineering and GE crops and foods across, so labelling is unlikely to be meaningful or an instrument of choice for farmers and consumers.

Agbiotech politics

India has followed the US model of regulation but lacks the scientific experience and stringency of the US system where biosafety is conducted under a voluntary, not mandatory regime. As a member of the US led ABSP I and II programmes (Agriculture Biotechnology Support Programme), India’s agenda and policy is heavily influenced by the US with respect to key concepts like substantial equivalence, precautionary principle, science based evidence vs socio economic impacts, centres of origin, liability and redressal regimes, etc. Even the initial policy on mandatory labelling of transgenic products sometimes shows signs of flagging.

Civil society groups like Gene Campaign have been pressing for a Europe style system based on the precautionary principle and strong public participation in decision making, with little effect so far. The government is even less likely to respond to such suggestions now given that it is strengthening its partnership in this field with the US. Recently (in March 2006), along with the agreement on nuclear technology, India has concluded an agreement on agriculture with the US called the ‘Indo-US Knowledge Initiative in Agricultural Research and Education’ to promote the so-called “Second Green Revolution” with its focus on developing transgenic technologies and products in agriculture. This agreement was concluded in great secrecy and without consultation with even key actors like the National Academy of Agricultural Sciences or the scientific cadre of the Indian Council of Agricultural Research. Political involvement in decision-making in agbiotechnology is practically non-existent. Bureaucrats and technocrats run the programmes arbitrarily, handing out grants and approving projects with no visible peer review process.

Against this, a successful campaign by agbiotech promoters has succeeded in associating the Gene Revolution with the Green Revolution, projecting it as an improved version of the same thing. This results in the political leadership viewing agbiotechnology as favourably as it does the Green Revolution which is perceived very positively for its contribution to end food imports and making India food sufficient. There is little understanding of the critical difference between the two, the former was a public technology, the latter is an entirely private technology, with complex and excluding IPR regimes.

Research agenda

Research on transgenic technology in India is continuing in both private and public sectors. Since there is no biotechnology policy, nor any process for setting research goals, there seems to be little coherence in the research

objectives. For instance, the Cry9c gene known to elicit allergic reactions and the reason why Starlink corn was banned for human use in the US, is allowed for use in research programmes. Approximately 40 per cent of research projects in the public and private sector are based on the Bt gene.

This will result in the presence of Bt containing crops in all sea-sons and it is likely that pest resistance will develop much faster than if a more judicious and restricted use were made of the Bt gene. All Bt cotton in India is being produced by the private sector and all as hybrids so that the farmer cannot save seed. India is the only Bt cotton cultivating country where it is being produced as hybrids; everywhere else, it is produced as true breeding varieties.

Why are the Bees Dying?

Suman Sahai

When I was at my university in Heidelberg this summer, the hot topic of discussion everywhere was the disappearance of honeybees. Media talked incessantly about the impending doom that would befall mankind if honeybees were to die. The quote of the month was Einstein’s …”If the bee disappeared off the surface of the globe, then man would have only four years of life left. . “No more bees, no more pollination, no more plants, no more animals, no more man.” The immediate fact is that millions of bees have simply vanished. Over the last few months bees are dying in the US at an alarming rate. Beehives are emptying out as bees are disappearing in hordes. The problem is so severe that it has been called the Colony Collapse Disorder (CCD).

In most cases, the hives are empty and the dead bees are nowhere to be found .The bees exhibit a set of symptoms, which scientists say does not match anything in the known literature. In many hives, evidence of almost all known bee viruses were found in the few surviving bees. Some had five or six infections at the same time and were infested with fungi -- a sign, experts say, that the insects' immune system may have collapsed. Curiously, other insects that would normally raid abandoned hives for honey and pollen stores, do not go near the hives exhibiting CCD. This suggests that there is something toxic in the colony itself, which is repelling other insects.

The estimated economic value that bees generate, by pollinating fruit and vegetable plants, almond trees and animal feed like clover, is more than $14 billion. Media reports on the extent of damage that will be caused to US agriculture if bees died out, has finally brought national recognition to a problem that beekeepers have been worried about for some time.

There is no understanding why the bees are dying. Several theories are mooted one being the varroa mite, introduced from Asia, another is the widespread practice in agriculture of spraying wildflowers with herbicides and practicing monoculture. Another possible cause, according to beekeepers is the controversial and growing use of genetic engineering in agriculture.

Walter Haefeker, Vice President of the European Professional Beekeepers Association speculates that besides a number of other factors, the fact that genetically modified, insect-resistant plants are now used in 40 percent of cornfields in the United States could be playing a role. The figure is much lower in Germany — only 0.06 percent. So the areas where the bees have disappeared are areas cultivating a lot of Bt crops. This is unlikely to be a coincidence.

A study conducted at the University of Jena from 2001 to 2004 provided evidence that bees infested with parasites and fed with Bt pollen were affected by the pollen and died at a high rate. In the Jena study researchers studied the effects of pollen from a variety of Bt corn on bees. The study found that the pollen of Bt corn had no impact on healthy honeybee populations. But when the bees used in the experiments were infected with a parasite, they died in large numbers. It is possible that the parasitic infection either lowered the immunity of honeybees or altered the surface of the bees’ intestine such that they became vulnerable to the Bt toxin.

The pest control strategy using the Bt gene is based on the action of the Bt endotoxin on the gut of pests like the bollworm. The Bt toxins kill the larvae of certain species of insects after being ingested by the larvae. These Bt toxins cause death by attaching to specific receptors in the larval gut, eventually rupturing the gut and killing the larvae in a few days. Bt toxins are thought to kill only the target pests because only the target pests contain the necessary binding receptors. However the experience of increased mortality in Monarch butterflies and lacewing beetles that were fed Bt pollen , show that what are considered non-target pests can also be susceptible to the Bt toxins.

US scientists working on transgenic crops are less willing to buy the theory of Bt pollen being responsible for the dying honeybees. Tracking the crisis of dying honeybees, scientists at the University of Maryland are of the view that the current use of Bt corn is not associated with CCD but concede that this possibility cannot be ruled out. They further admit that although there is no evidence so far of any lethal or sub-lethal effects of the currently used Bt endotoxins on honey bees, insecticidal products expressed by other transgenes in crops may need extended field testing to assess the longer term consequences of sub-lethal changes in colonies and subtle modifications in bee behavior. This kind of testing should be extended to other kinds of insects as well.