Biotechnology regulation at the crossroads

The biotechnology industry was jubilant when its calls for a relaxation of regulations on the contained use and deliberate release of genetically modified organisms (GMOs) were endorsed in October by a report from the House of Lords Select Committee on Science and Technology.1 The report's outspoken recommendations in favour of cutting red tape in order to unleash the industry's promised wealth-creating potential have perplexed regulators who say they were already doing most of what it recommends. And some scientists are unhappy at the way in which the Committee dismissed as "conjectural" the concerns about GMOs' potential to damage the environment voiced by the Royal Commission on Environmental Pollution (RCEP) four years ago.

The potential risks associated with genetic modification have been exercising scientists, industrialists and regulators since the early 1970s. In a reversal of the history of other technological developments, scientists themselves called for a moratorium on certain aspects of experimentation as they became aware of biotechnology's startling potential - and its capacity to cause adverse consequences if adequate controls were not applied.

US moratorium
The call for a moratorium originated from the US National Academy of Science in 1974. In the UK, the Advisory Board for the Research Councils responded in 1975 by giving the go-ahead to the use of genetic modification techniques because of the important benefits they offered, but with the proviso that such research should be subject to rigorous controls.

That philosophy has essentially formed the basis for controls since then, with the introduction in 1987 of a statutory requirement for case by case notification to the Health and Safety Executive (HSE) and the Genetic Manipulation Advisory Group of any activities involving genetic manipulation. A relaxation of the notification rules followed in 1989 for activities perceived to be of low risk.

The HSE estimates that some 20,000 activities involving GMOs have been carried out in the UK since 1987. But the 1989 rules, like their predecessors, were established under the Health and Safety at Work Act, and their scope extended only to protection of humans rather than the environment.

RCEP urges caution
The risks associated with the release of GMOs to the environment were specifically addressed for the first time in 1989 by the Royal Commission on Environmental Pollution (RCEP). Its report argued for caution. "Concerns in the 1970s about the safety of genetic engineering work in laboratories led to stringent containment arrangements which have gradually been relaxed as confidence has increased," it said. "As large gaps still exist in knowledge about behaviour of organisms in the environment, an initially cautious approach, taking account of the ingenuity that scientists will apply in the development of new organisms, is the responsible way forward."

Among the possible adverse consequences highlighted by the RCEP were:

  • Genetically modified viruses developed as pesticides might inadvertently have their virulence altered or "attack" non-target species.

  • Plants engineered to kill insect pests might prompt the development of resistance among the target species to the particular toxin used.

  • Herbicide resistance genes in crop plants might be transfer-red to weeds, making them also resistant to the herbicide.

    The RCEP's key recommendation was that applications for consent to release GMOs to the environment should be scrutinised on a case by case basis by an expert committee for every stage of release until regulators had gained confidence in the risk assessment procedures used (ENDS Report 174, pp 11-13). The Advisory Committee on Releases to the Environment (ACRE) was established in response to its recommendation, and new statutory powers to control releases of GMOs were incorporated in the Environmental Protection Act 1990.

    However, the RCEP foresaw a situation when "in the light of experience the licensing authorities may consider it to be safe to issue a release licence for a class or category of related GMOs" - a procedure which would enable consent to be granted without going through ACRE. The Department of the Environment (DoE) eventually responded to the report this summer (ENDS Report 222, pp 38-39 ).

    EC regulations
    Meanwhile, in 1990 two EC Directives on GMOs were adopted. One dealt with contained use of modified micro-organisms, the other with deliberate releases to the environment (ENDS Report 185, p 34). The Directives borrowed heavily from the risk assessment procedures formulated by the OECD in a 1986 report known as the "blue book". The report distinguished between low-risk activities involving inherently safe organisms and those involving more hazardous organisms and suggested guidelines for carrying out such work accordingly.

    The EC Directives were brought belatedly into force in the UK on 1 February this year. Both sets of regulations are enforced by the HSE, which acts on behalf of the Department of the Environment (DoE) on releases to the environment under the terms of a memorandum of understanding.

    These arrangements had hardly been given time to settle down before the Lords Committee embarked on its inquiry into biotechnology regulation (ENDS Reports 220, pp 27-28 , and 221, pp 33-34 ). Its focus was primarily on the two EC Directives and the general concept of whether products based on GMOs should be subject to a unique "horizontal" risk assessment procedure concerned with the process in addition to the "vertical" safety regulations already applied to specific product sectors.

    Industry allegations
    The spur for the inquiry, the Committee says, were the "allegations by industry that recent changes in the regulations governing biotechnology both in contained use and following deliberate release into the environment were likely to place UK industry at a competitive disadvantage," especially against firms in the USA and Japan.

    The report duly concludes that "the benefits of biotechnology are already well proven; biotechnology and products of biotechnology are with us to stay and these products are likely to yield enormous future benefits to mankind". But "regulation places UK biotechnology research and investment at a competitive disadvantage vis \'e0 vis our principal overseas competitors."

    In arriving at this conclusion, the Lords accepted the pleas of companies such as Zeneca, the biosciences firm created recently by amputation from its parent, ICI.

    In its evidence to the inquiry, Zeneca says that until the late 1980s the UK "was developing a regulatory system that protected both man and the environment while encouraging investment in research and industry." However, implementation of the two EC Directives "has impeded the conduct of research and development in both academic and industrial sectors and there is no evidence that safety has been increased. This is because the Directives appear to be based on the concept that genetic modification per se poses unique risks to man and the environment and therefore must be controlled in a unique manner. In addition to the damage to our academic and industrial competitiveness, the debate has done nothing to build public confidence in the regulatory system."

    Regulations panned
    The Committee swallowed this argument and uses colourful phraseology to describe the regulatory system. The deliberate release regulations are a "bureaucratic nightmare". Those on contained use are "fundamentally unscientific". And the RCEP's concerns about GMO releases are dismissed as being based on "conjectural" risks and "false analogies". By comparison with this terminology, though, the Lords' recommendations are moderate.

    On deliberate release, the key recommendations are that the EC Directive "be amended to enable certain activities, selected by a group of EC national experts, to be subject to a vastly accelerated and simplified procedure of notification on United States lines." The Government is also urged to press the European Commission to revise a questionnaire on the risk assessments carried out by applicants so that it is more specific to the type of organism proposed for release. And the DoE is urged to shorten the time taken to grant consents for plants so that applicants do not miss growing seasons.

    The Committee was pointed to the US regulatory system by numerous biotechnology businesses. There, the federal government decided from the outset that there was no need for new regulations specific to biotechnology. Instead, all products are controlled under existing statutes on plants, animals, pharmaceuticals, pesticides, toxic substances and the like.

    Perspectives on US system
    Biotechnology firms pointed enviously to a recent decision by the US Department of Agriculture to exempt six crops which have been genetically modified in specific ways from the need to obtain a prior consent for release. The USDA believes that it has enough experience with these from field trials to exempt them. The six crops, which are not indigenous to the USA and therefore pose little risk of transferring genes to weedy relatives, are potato, corn, tobacco, cotton, soya bean and tomato. Others are likely to be added to the list.

    What the Committee apparently did not delve into were the problems associated with the US system. One of these is that regulators have had difficulty in squeezing biotechnology products into existing regimes which do not always have sufficiently relevant risk assessment procedures. A case in point is the classification of plants carrying Bacillus thuringiensis toxin genes which make them toxic to insect pests as "pesticide plants" in order to bring them under existing pesticide regulation. Another example is the lack of any existing body of regulation to cover the release of genetically modified fish.

    Apart from criticising the superficiality of the Committee's comparison of the US and EC regulatory systems, the DoE has also been irritated by its failure to take note of action already in the pipeline to make the UK and EC controls more industry-friendly. Last year's White Paper on the environment promised "streamlined procedures to expedite the clearance of safer types of GMOs". And a "`fast-track' for no risk GMOs" was to be pursued at EC level.

    Streamlining initiatives
    These initiatives are well under way. The deliberate release Directive enables Member States to seek clearance from a committee of officials to introduce streamlined consent procedures for categories of GMO release on which sufficient experience has accumulated. In September, the committee agreed a set of criteria for judging such applications and is now ready to examine fast-track protocols submitted to it.

    The DoE says it is preparing recommendations for reducing the bureaucracy of the consent procedure and hopes to have these cleared by early next year. One suggestion under consideration would allow a single consent to be awarded in cases where a firm wants to release several GMOs at several sites, whereas at present two separate consents are needed to release one GMO at several sites or several GMOs at one site. The European Commission says it expects to receive proposals for fast-track procedures from a handful of Member States and says it hopes to persuade the others to adopt one of these as models in order to avoid 12 different fast-track systems.

    The Directive also provides for the amendment of its technical annexes using the same committee procedure. Member States have now almost agreed on a simplified risk assessment questionnaire for genetically modified plants. Similar moves are said to be under consideration for other organisms.

    Fast-track consents
    In the UK, the DoE is also planning to introduce a new category to its existing approval procedure in conjunction with ACRE which would provide a fast-track for low-risk releases "without diminution of environmental protection."

    The current position is that releases of organisms with which ACRE has no experience or which are judged to present a high risk would be submitted to it for full scrutiny, with a decision on the consent expected within the 90-day period laid down by the Directive. In cases where the organism is not of low hazard but is judged to present no or little risk if its release is well managed, ACRE gives its consent by means of a postal system with a target turn-around time of 50 days.

    The new procedure would require ACRE to decide on categories of organism considered to be intrinsically safe and issue generic advice on the management of their release, enabling a consent to be issued without consulting ACRE within a target time of 30 days. An example that might fall into this category would be genetically modified corn with no new allergenic or toxic properties. This new procedure would be similar to the USDA's fast-track approval system. Other, less radical initiatives are likely to be introduced within weeks to cut some of the paperwork and provide further guidance for applicants.

    Thus the Lords' recommendations were already being addressed, leaving DoE and European Commission somewhat bemused as to what more they are expected to do.

    Horizontal v vertical
    The need for across-the-board legislation for all uses and releases of genetically modified organisms - so-called "horizontal legislation" - was a major theme of the inquiry. The outcome is a series of recommendations from the Committee that the controls should rapidly be transferred from the horizontal to the vertical, as provided for in the two Directives; that horizontal legislation should be retained only for research and development in "limited areas where regulation is required", such as deliberate releases of GMOs outside the low to negligible risk category; and that work on any further horizontal EC Directives "should cease forthwith."

    The report also urges that wherever a GMO-derived product is not capable of reproducing and can be fully characterised, it should be subject only to a sectoral regulatory regime under existing product legislation. This recommendation has also bemused regulators, who point out that the deliberate release Directive only applies to organisms that are capable of reproducing. Non-viable organisms would therefore in any case come under existing product regulations.

    The arguments for and against horizontal legislation were well rehearsed by the end of the inquiry. Biotechnology practitioners are keen for the technology not to be perceived by the public as anything out of the ordinary, and argued that in some respects it is safer than traditional techniques in, say, plant breeding because gene modification is a much more accurate method offering more predictable results.

    Some industrialists even suggested that within product-specific legislation there should be no separate risk assessment procedure that discriminates between products derived from genetic modification and those that are not. At the end of the day, they argue, it is the safety of the product that should be assessed, regardless of the process used to make it.

    On the other side of the divide are those - among them environmental groups and some regulators - who say that capabilities such as being able to transfer a gene from an animal to a plant make the technology different to anything that has gone before.

    In his evidence to the inquiry, Dr Julian Kinderlerer of the Department of Molecular Biology and Biotechnology at the University of Sheffield and a member of ACRE noted that "modifications of micro-organisms using techniques other than recombination are not regulated, although risk assessments are required. Most of these techniques are crude and do not provide the same control over the introduced modification as that resulting from recombination.

    "In general, however, material from unrelated organisms is not introduced using these techniques. It has been argued that the changes made using these traditional techniques could have occurred naturally during the millions of years of evolution. That problems from these changes have not been encountered suggests that induced mutational events are not dangerous.

    "The argument ignores two points. Firstly, it is clear that pathogenic organisms have evolved, and secondly, an infinity of time has not yet occurred, and all modifications that might have arisen spontaneously have not yet happened. The argument for not regulating modified organisms because we do not regulate un-modified organisms could be turned over to - why not regulate the traditional processes?"

    Safety net
    Those who favour horizontal legislation for processes involving genetic modification point out that the existing regulations do not in any case preclude an eventual move to product-based legislation. The deliberate release Directive contains a "self-destruct" clause whereby as soon as product-based legislation for any particular sector is considered to provide "a specific environmental risk assessment similar to that laid down in this Directive" than the horizontal Directive should cease to apply.

    But they also point to the situation that sometimes arises where genetic modification techniques are used in research with no clear idea as to their eventual applicability. In this case it would not be possible to apply product-based legislation because there would be no "product" to assess. They believe that an essential purpose of horizontal legislation is to act as a "safety net" while identifying those high risk activities that will need closer scrutiny than others. A further advantage of such a system is that its administrators accumulate expertise and knowledge in judging risks which would otherwise be dissipated in a product-based approach.

    But the Lords were unconvinced by such precautionary arguments, especially in the "acrimonious debate over the deliberate release of GMOs." Their report states that "here again some of our most eminent scientists assured us that fears were largely misplaced. The hazards identified by environmentalists, by the DoE as regulatory authority, and by the RCEP are conjectural." Many of these, the Lords conclude, are based on "false analogies" with ecological mishaps that have arisen through traditional plant breeding, which neglect the "greater precision of the techniques of genetic manipulation."

    The report goes on to explain how certain allegations were unjustified. One is that genetically modified plants could have a competitive advantage and become pests. But the Committee maintains that scientists do not know how to deliberately create weeds, and the probabilities of doing so by chance are slim. And in any case, genetically modified plants generally tend to survive less well than non-modified strains and tests can be carried out to predict whether they will be more aggressive.

    Another risk is that "gene pollution" may spread to indigenous populations - for example, making weeds herbicide-resistant. But the report states that traditionally bred plants pose as much risk of this as genetically modified plants - and if this did happen then a different herbicide could be used to control the weed. A third risk is that modified plants or animals might be genetically unstable and unexpectedly develop dangerous properties, but practitioners assured the Lords that "genetic stability is a prerequisite in any breeding programme."

    Selective use of evidence
    One expert in the field of deliberate release of GMOs is Professor Mark Williamson, a population biologist at the University of York. The Lords' report cites his written evidence in arguing that "the vast majority of the biotechnological developments that are known about at the moment will have no safety implications for the environment."

    In fact, this is a misquotation of Professor Williamson's evidence, which actually says such developments "will have no new safety implications for the environment." And his evidence continues: "However, there is a small possibility of a major environmental effect. More immediately, several of the products being developed could well have undesirable side effects. For instance, the promotion of herbicide resistant sugar beet is likely to exacerbate the weed beet problem. Weed beet is a form of beet which is a result of bad agricultural practices, and a clear example that agriculture does do harm to the environment on occasion."

    Professor Williamson goes on to point to other potential problems, such as the development of toxin-resistant strains of insects as a result of widespread use of plants engineered to produce their own toxin, and the potential for genetically engineered viruses to affect non-target beneficial insects.

    In addition, he makes a general observation on the application of biotechnology to date. "It is particularly unfortunate the industry has gone for herbicide resistant plants as one of its main lines of developments, as these inevitably require the use of herbicide. There are arguments about whether this will mean more or less herbicide, but the fact that the herbicide will be used is incontrovertible. What environmental biologists would like to see in this field is the development of products that lead to the decreased use, or even cessation of use, of harmful chemicals of all sorts."

    Professor Williamson sympathises with industry's case that the two EC Directives are overly bureaucratic. But he nonetheless has reservations about relaxing case by case assessments of release applications too quickly. For instance, most experience of releases of genetically modified plants has been on a small scale and may not have revealed all the problems that may arise once they are grown for commercial purposes. He also notes that in the past, performance or environmental problems have sometimes not emerged until several generations of a crop have been grown.

    Professor Williamson says his evidence was used selectively by the Committee. He told ENDS that on the whole he felt that the RCEP's inquiry painted a more "gloomy" picture of the potential risks associated with releases of GMOs than was perhaps necessary - but that the Lords' report has painted an excessively "sunny" picture. On the whole his view lies closer to the RCEP's. The RCEP is also understood to feel that its conclusions were somewhat unfairly treated by the Committee, particularly as its own report included a recommendation for relaxation of controls as experience was gained.

    Funding, patent problems
    Notwithstanding the divergent perceptions of risk associated with biotechnology, an important point about the Lords' inquiry is that its terms of reference confined it to examining the effect of regulation on the UK biotechnology industry's competitiveness. But in fact, as the Committee concedes, the regulatory climate is by no means its only hindrance.

    Other factors that appear to be at least as important to the industry's competitiveness were cited by several witnesses to the inquiry. They include the difficulty of raising venture capital to fund the start-up of biotechnology companies, and the inefficient transfer of new ideas and technology from academia to the commercial world, especially in comparison to the sophisticated technology transfer operations in the USA. The advantage conferred on US firms as a result of differences between US and European patent laws is another significant factor in the equation.

    Regulation may be perceived as a natural enemy of a rapidly growing industry, but in the long run it is also a crucial ally. An effective regulatory system serves to reassure the public that they are not being exposed to unassessed and unacceptable risks. Naturally there is room for debate about what form that regulation should take - but the danger in relaxing the current regime as precipitately and as comprehensively as some in the biotechnology business would wish is that it could take only one serious incident to undo all the work done by the regulators in building public confidence in biotechnology.

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