Code Number:AU99016

Huge potential of genetically improved plants outweighs hypothetical risks
CS Prakash, Tuskegee University, Alabama, US email: prakash@tusk.edu

Looking at the recent developments in India from a Centre for Plant Biotechnology Research that I head in an American campus (and there are many like me in biotechnology in US academia and the biotech industry), I am struck by how a small group of Indian activists (with strong Western connections) opposed to biotechnology have been making headlines virtually unopposed. They are on the warpath against genetically improved crops. And through well-orchestrated campaigns are sowing the seeds of fear in the minds of the Indian public.

Their goal is clearly to intimidate policy makers by twisting facts about biotechnology and vilifying its proponents. Fields trials of genetically improved crops have been burnt without regard to the views of their farmer-owners and some of the most absurd and wild rumours about the risks of biotechnology have been meticulously spread with appropriate sound bites. Strangely, neither the media nor intellectuals from outside the scientific community have chosen to challenge the basis of such claims. Risk is essentially a function of the nature of a product, and not the process employed in developing the product, according to Andre de Kathan of the University of Hanover, Germany.

Products from biotechnology are no less safe than traditionally bred crops. In fact, they may even be safer as they represent small, precise alterations with the introduction of genes whose biology is well understood. Often these genes are derived from other food crops.

Genetically improved products are subjected to intensive testing, while conventional varieties have never been subjected to any such regulation for food safety or environmental impact. Traditional methods of developing crops involve wild crosses with weedy relatives of crop plants. Hundreds of unknown genes, of whose traits we have little knowledge, are introduced into these food crops through these conventional plant breeding methods.

Many characteristics such as disease and pest resistance have been routinely introduced into crop plants from their weedy and distant relatives over hundreds of years. These have posed no serious threat to the environment in terms of crop invasiveness, gene flow to weeds or the biodiversity. Yet, some of these fears are invoked for genetically-improved crops which possess similar traits, but are developed through a rapid genetic modification processes.

Thousands of new plants have been introduced into India since Vasco da Gama, and no one now questions the invaluable impact these exotic introductions have made on Indian agriculture, food habits and the economy. These include chilli, wheat, potato, tomato, cabbage, groundnut, cowpea, apple, grape, eucalyptus, rose and countless ornamentals. Genetically improved crops, on the other hand, do not involve any such wholesale introduction of thousands of new genes through new plants, only alteration of just one or two genes with known traits in the already popular Indian crop varieties.

There is, therefore, a far greater risk to the Indian society from the non-acceptance of biotechnology when compared to the minuscule risks posed by genetically improved crops. The enormous potential benefits from these crops therefore far outweigh any hypothetical risks posed by their use. Genetically improved plants are safe Thousands of field tests conducted so far on various genetically improved crops with more than one hundred new traits, or their commercial planting on 28 million hectares world-wide have failed to provide any serious evidence of food safety or environmental concern. Gene altered corn and soyabean products, including baby food, have now found their way into nearly 4,000 food products in American supermarkets. Yet, not a single issue of food safety has been reported. It should be pointed out that American standards of food safety are the highest in the world. The regulatory agency, the Food and Drug Administration (FDA), has one of the world's strictest standards and thus enjoys considerable public trust.Many genes used in genetically improved crops, such including the Bt gene isolated from soil bacteria, have a long history of perfect safety and ecological record. Further, many genes introduced into crop plants (such as those used to develop slow ripening tomato) are derived essentially from the same crop but inserted in a reverse manner to silence the undesirable genes, so as to slow down the ripening in tomato or prevent cyanide production in cassava.

This is not to say that genetically improved crops will not have any unforeseen effects. But the possible negative effects of each crop should be scientifically evaluated on a case-by-case basis, and the regulatory system should evolve over time based on new knowledge. As India is the centre of the origin of many crop plants with many wild relatives, we should be prudent to minimise any potential gene transfer to weedy relatives.

Many of these concerns are technical issues that could be addressed through appropriate research, and not through emotive debates or militant activism. A frequent fear invoked against the use of genetically improved crops is their possible impact on the environment. What can be more environmentally friendly than a crop variety that requires little or no pesticide? How can a crop variety that is three-fold productive, and thus decreases the pressure to cut down forest lands for agricultural expansion, be against nature? Yet, one hears that `biotechnology is incompatible with nature' and is `not natural'. We need to remember that agriculture is inherently an unnatural activity. Human beings since the dawn of civilisation have been meddling with nature to provide the needed food, fibre and shelter for the sustenance of humankind. None of our present day crops resemble their weedy relatives. Nor would they survive in the wild as they have all been altered substantially through selection by farmers over thousands of years to be more adaptable and productive.

A similar situation exists with livestock and poultry and, for that matter, even our pets like dogs and cats. Genetically improved crops are a logical extension of this human activity, and thus are no more unnatural than what has been practiced for aeons. Suman Sahai of Gene Campaign, New Delhi has rightly reminded us that we should harvest the power of science and technology to improve the living conditions of our people and our most ethical drive is in alleviating poverty, hunger and starvation death.

What the experts say

Norman Borlaug, Nobel Laureate and `Father' of Green Revolution: "The world has the technologyeither available or well-advanced in the research pipelineto feed a population of 10 billion people. The more pertinent question today is whether farmers and ranchers will be permitted to use this technology. Extremists in the environmental movement from rich nations seem to be doing everything they can to stop scientific progress in its tracks."

Jimmy Carter, ex-President of the USA: "Instead of reaping the benefits of decades of discovery and research, people from Africa and South-east Asia will remain prisoners of outdated technology. Their countries could suffer greatly for years to come. It is crucial that they reject the propaganda of extremist groups before it is too late."

Ismail Serageldin, World Bank, CGIAR: "Biotechnology will be a crucial part of expanding agricultural productivity in the 21st century. If safely deployed, it could be a tremendous help in meeting the challenge of feeding an additional three billion human beings, 95 percent of them in the poor developing countries, on the same amount of land and water currently available."

The World Bank Panel that included Prof MS Swaminathan: "Transgenic crops that are developed and used wisely can be very helpful, and may prove essential, to world food production and agricultural sustainability".

Suman Sahai, Gene Campaign, New Delhi: "Keeping pace with the growing importance of biotechnology and its potential to address some of our urgent food and health care needs, a spurious and somewhat bogus debate on bioethics has been started in India. This debate with its plagiarised metaphors and rhetoric borrowed from the West is not Indian in context or substance, and far from relevant."

G Padmanabhan, Ex-Director, Indian Institute of Science: "Transgenic technology and conventional wisdom need not be considered as mutually exclusive. The country needs dynamic entrepreneurship leadership in agriculture and no one needs to feel exploited. There is a need for scientists, enlightened administrators, progressive farmers and people's representatives to come together to spread the correct message about transgenic technology."

(The author is professor and director of the Centre for Plant Biotechnology Research at Tuskegee University, Alabama, USA. He is the founder of the `Society for Biotechnology' in Bangalore, and is among the founding members of an Internet-based network called PBASIO the `Plant Biotechnologists and Agricultural Scientists of Indian Origin' which has more than 800 members and promotes discussion on agbiotech related issues concerning India.) 

Scientists in both research and commercial environments suffer the competing pressures of the need for early publication to establish or solidify their career, and the legal requirement not to publicly disclose the invention until a patent application has been filed. However, in order to file a valid patent application, the applicant must provide information (which may require substantial time consuming experimentation) in exchange for the monopoly provided by a patent. This legal requirement conflicts with the interest of the applicant to obtain the earliest possible filing date to establish the priority of the inventor's rights. This is of particular concern in highly competitive and fast moving fields. This article seeks to identify the mechanisms and difficulties associated with including information after the initial application in Australia, and the major jurisdictions of Europe and the US.

Typically, inventors feel that once they have filed a provisional application, they are free to disclose the invention. However, after the provisional is filed, the inventor normally still does research to further refine the invention, and therefore generates data of relevance to the application. Consider a novel protein, which has been identified and has been shown to have in vitro activity thought to be of benefit in particular diseases. The inventor may wish to publish his work, and will therefore request the filing of a provisional application, followed 12 months later by filing of a complete application. Naturally, the inventor wishes to gain protection for the protein when used as a human or animal therapeutic. It is a legal requirement that the information in the patent application is sufficient to enable a person skilled in the relevant field to carry out the invention (sufficiency), and must adequately demonstrate that the invention is useful for the purpose disclosed (utility). As a result, filing an application too early, when there is not sufficient data to demonstrate sufficiency or utility, may adversely affect the validity of any patent granted on the application. Generally experiments which demonstrate first principle in vitro are not considered sufficient to support a claim to a therapeutic pharmaceutical, in animals or humans, in any major jurisdiction. Pre clinical tests in animals are usually considered sufficient disclosure on which to base a claim to a human therapeutic. Therefore, patent offices in various jurisdictions will usually require this type of disclosure to grant a patent having claims to a human therapeutic.

There are two major issues affecting an inventor filing an application containing only in vitro data. Firstly, the risk of invalidating the application by publicly disclosing later results which may not be considered "fairly based" on the data included in the application. Secondly, the issue of whether data can be added during prosecution of the application, to support claims to a therapeutic.

What information can be publicly disclosed after filing?

An inventor must be careful when filing limited information in a provisional application, then disclosing further results prior to the filing the "complete" application. If the information disclosed between the filings is not "fairly based" on the information in the provisional, the disclosure may invalidate any patent granted on the application. Using the above example of a novel protein, if new properties are identified, or the in vivo properties are "surprising" in light of the in vitro properties disclosed in the provisional application, these properties are unlikely to be fairly based on the provisional application. Disclosing the data publicly (eg at a conference) prior to the filing of the complete application may invalidate any patent granted on the application. A similar problem arises in respect of a complete application, if data which is publicly disclosed did not form part of the original application, but is added later. The exception is the US where, provided an application covering the contents of the disclosure is filed within 1 year, the disclosure will not invalidate any US patent granted on the application.

What data can be added later?

The issue of adding data to a complete application will be discussed with respect to Australia, the US and Europe.

For example, in Australia when a complete application is filed with only in vitro results, it is relatively easy to amend the specification, particularly during prosecution, and add further examples to support the claim to a therapeutic. Provided the new matter is "fairly based" on the matter as filed (that is, generally shows the expected results), the priority date will not change. However, some concerns regarding the validity of the application may remain as the original disclosure may not have sufficiently disclosed the use of the molecule as a therapeutic. If the results in vivo would not have been predicted from the in vitro results, it would be best to file a separate application, otherwise the priority date of the application will change to the date of the addition of the matter.

In the US, new data can be added as a continuation in part (CIP) application of the original. Again provided the new data does not show anything surprising above the matter as originally filed, the priority date of the CIP will remain the same. However, the priority date will be different if the new data added is surprising over the original disclosure. One disadvantage of adding data in a CIP, is that the filing of a CIP will delay grant of a patent, and therefore delay the opportunity to initiate an infringement action based on the patent. There may also be concerns regarding the validity of the application, as the original disclosure may not sufficiently describe a therapeutic use of the molecule.

In Europe, no new matter can be added after filing. As a result, when an application is filed with in vitro data only, an applicant who wishes to claim a therapeutic must rely on evidence of a high correlation between the in vivo and in vitro results. This strategy will carry some risk that the application does not adequately describe the invention both in terms of demonstrating the utility as a therapeutic, as well as sufficiently describing the use as a therapeutic. No further patent application disclosing in vivo results can be filed because, unless the in vivo results are surprising, the claims to a therapeutic will not be inventive over the original specification. Accordingly, the consequence of filing a patent application without adequate supporting data is most serious in Europe where doubts about the validity of the specification will remain and no new matter can be added.

The conflict between an inventor's legitimate requirement to file an application as early as possible, and the relatively long lead times between the identification of a molecule with therapeutic potential and the demonstration of this potential in animals, is a continuing issue which requires individual consideration. Particular consideration must be given to each jurisdiction of importance.

Copyright 1999 Australian Biotechnology Association Ltd.