Guide to Risk Assessment and Biosafety in Biotechnology, GRABB

An Initiative of the United Nations Environment Programme (UNEP)




National Appraisal and Monitoring


Gilbert Howe


Contact: IRRO Secretariat



Risk and its Perception

Who should assess and manage risk?

National safety committees

Institutional (local) safety committees

Oversight in developing and developed countries

Sources of guidance for committees

The role of public opinion

 Overview Risk and its perception Who should assess and manage risk? National safety committees Institutional (local) safety committees Oversight in developing and developed countries Sources of guidance for committees The role of public opinion


This chapter has two purposes. The first is to describe in outline the functions obe in outline the functions of those national bodies that oversee releases and other GMO work, and the second is to consider in rather greater detail the analogous role of the local bodies that are in touch with day-to-day events in the workplace or field station and that are often answerable to their national counterparts. Many readers of this Guide may be members of the latter kind of organization, or may be actively seeking to set one up. A few may be involved at the national level. Before looking at these groupings (it has become customary to refer to them as committees, reflecting the mode in which they normally operate) we shall need to consider the concept of risk with which they are centrally concerned, and to ask where the tasks of risk assessment and management should lie.

Risk and its Perception

At the heart of all notions of biosafety lies the thought, whether of a single individual, a team of workers, a public interest group or a government, ternment, that a procedure in applied biology carries a threat to human or animal health or to the environment. In some instances this perception is related to a particular ethical viewpoint, and sometimes the perceived risk is balanced against some hoped-for benefit that is also conjectural. But if risk perception is to be translated into effective risk management some grouping of experts and public representatives must be consulted to advise on whether the perception is justifiable, and if so, how the risk is to be managed.

The assessment of biological risk is necessarily a subjective matter (see Sections Concepts and Theory of Risk Assessment, Applying Risk Assessment Theory, Current Procedures for Applying Risk Assessment), not only because of the unpredictability of chance events but especially because of the novel nature of much biotechnological work. Assessors of the risk of events such as fire, theft and automobile collision, whose task is usually the setting of insurance premiums, hamiums, have access to vast collections of data on past occurrences in different areas from which a reasonable estimate of future mishaps can usually be made. Twenty years experience of applied genetic modification has allowed us to assemble some information of this kind for biological risk (see below), but safety committees have also attempted to evolve analytical techniques (see pp. for Access/Expression/Damage and GENHAZ) for assessment. In general these assess the likelihood of a combination of very low risk events that might together constitute risk of an unacceptable level, or at least one requiring a higher degree of containment. The notion of acceptability is crucial here: it will always be unrealistic to aim for the assurance of zero risk, but the devising of suitable containment and monitoring procedures may be felt to render an admitted degree of finite risk tolerable. In this way the deliberations of safety assessors can substantially help in allowing humanity to reap the benefits of biotechnology chnology research while not paying an unacceptable price in economic, health or environmental damage.

Who should Assess and Manage Risk?

There are in principle three levels at which consultative and regulatory processes can give rise to the guidance, and perhaps rules, which govern the acceptability of an experiment involving either recombinant DNA or a release (whether of a recombinant or of any exotic organism): local, national, and supra-national. For many countries national law is the principal force that drives thinking about biosafety issues simply because a breach of the law carries a prescribed sanction, and the frequent complexity of the scientific issues points to the need for national committees with appropriate expertise. Countries in which there is extensive experience of GMOs and their release to the environment have evolved well-established (albeit changing) regulatory frameworks which generally derive from legal systems with provisions inteions intended to protect workers and, more recently, which reflect concerns about the environment including the public at large. All frameworks of this kind, whatever the legal background, recognize the important role of consultation at the local level both in ascertaining the realities at a particular experimental site and in transmitting safety guidance to where it matters. Hence the need for both national and local committees.

Some countries may have little or no legal framework even though there is a strong sense of environmental concern, and these may wish to devise mechanisms for evaluation of proposals for releases in the light of the growing body of experience of such experiments, using local biosafety committees with a reasonable concern for their own communities.

The call for guidance at supra-national level arises both because of a desire to share national experiences and, perhaps more importantly, to provide for consideration of what might happen when an organism in one country ie country is released in another, either by accident or design. The role of supra-national codes is addressed below.

It will be noted that this discussion variously refers to guidance, regulations, and so forth. The actual word used will depend on the context: a national body may well be acting as prescribed by a specific law (or act) which in turn leads to formal regulations. Terms such as code and guidance carry somewhat less legal force but still have the implication that an experimenter should be ready to state a well-argued case for modifying or ignoring them. In the UN system the term voluntary code was used for the 1991 UNIDO-sponsored code of conduct to stress the intention of assisting countries rather than binding them with a document produced as part of a UN Convention. At the least prescriptive end of the scale is framework.

National Safety Committees

The first national biosafety committees were set up shortly after the discussion of tcussion of the first successful recombinant DNA experiments at the 1973 Gordon Conference (reference., perhaps to Morgan & Whelan p. 185: see Jim Watson's paper). The concerns of several scientists at that time led in due course to a self-imposed moratorium by those involved, both because of the conjectured risks inherent in cancer virology and the then new field of genetic engineering, and perhaps even more because of fears of the workings of public opinion. From these beginnings came national advisory bodies such as the Recombinant Advisory Committee (RAC) in the US and the Genetic Manipulation Advisory Group (GMAG; later Advisory Committee on Genetic Modification, ACGM) and Advisory Committee on Releases to the Environment (ACRE) in the UK. During the past quarter century several countries have set up analogous bodies, sometimes under the legal structures of supra- national groupings such as the European Union (EU): the EU issues directives which are required to be incorporated into the laws of member f member countries, and two such directives address biosafety issues.

The prescriptions of these national committees are often very detailed and they may require correspondingly detailed risk assessments and risk management protocols from the local safety committees that report to them. They are frequently issued as individual Notes of Guidance for the use of local committees that can be updated as and when required. There is a current trend, as data on releases and contained work accumulate, to try to discriminate "low risk" work where the element of conjecture has been gradually replaced by experience as needing minimal reporting and control, allowing attention to be concentrated on ostensibly higher risk proposals. The very low rate of occurrence of "accidents" can be construed either as a tribute to the effectiveness of the national/local committee system or as an indication that the whole structure was unnecessary in the first place, but the continuing high level of public concern (see below) anbelow) and the extension of genetic modification into areas such as human gene therapy makes it unlikely that the latter view will prevail at an early date.

Institutional (Local) Safety Committees

The activities of national committees are likely to be limited to generalities unless they are connected in some way to the realities of the laboratory or field station: local safety committees (institutional biosafety committees in US usage) are seen as of great importance by supervisory bodies such as ACGM and ACRE. It is considered important that they should be primarily or exclusively concerned with advising on genetic modification and/or releases, although a local committee may be constituted as a sub-committee of a more general group dedicated to all aspects of safety in the institution (including radiation, chemical safety, etc.).

The national body must first be notified of the intention to carry out relevant work and a local committee establishedestablished before this is done. The typical constitution of a UK committee would be:

(Source: GMSC Note...)

The procedures followed by a local committee are in general as follows:

(Note ACRE recommendations as well as ACGM ones.)

The details of membership, terms of reference, agendas, and full minutes should be widely publicized, and the meetings open to all who have a reasonable concern with agenda items. Copies of relevant legislation and of Notes of Guidf Notes of Guidance should be readily available to members and those making enquiries. It should be noted that provision for post-experimental clean-up and site monitoring, perhaps extending over several years, is of great importance in release experiments.

The most specialized of the tasks facing the local committee are those of risk assessment and containment. The guidance notes issued by bodies such as ACGM and ACRE specify both the appropriate containment level and the work conditions appropriate to it for each quantified risk, so that the committee's attention can focus on the risk itself. Other chapters in this Guide describe approaches to this, but it can be noted here that one of the earliest and simplest of procedures for contained work, and one which still contributes to risk assessments in the late 1990s, is to consider each proposal from three viewpoints:

By assigning a risk factor to each of these and then multiplying the three figures together a single overall factor is obtained and the appropriate containment level is assigned accordingly. The committee may well be able to recommend changes in the experimental protocol that will lower one or more risk factors and hence lower the degree of stringency of the proposed containment: for instance, the use of a debilitated organism or a cloning vector incorporating a "self-destruct" feature can materially lower the likelihood of access.

A much more complex approach is to use the procedure known as GENHAZ


Oversight in Developing and Developed Countries

The national an>The national and local committee structures described here are fairly typical of countries with differing degrees of economic development but all with some years' experience of releases and other work with GMOs. The view is sometimes expressed that biosafety committees and the codes by which they operate are luxuries for economically advanced countries able to take a long-term view of the effects of biotechnological development, and that their establishment detracts from higher short- term priorities such as famine relief. Many workers in developing countries, however, where there is sometimes neither a local committee structure nor any national coordinating body, have viewed with some concern their vulnerability to genetic "accidents" and to exploitation by interests attracted by the possibility of operating in a climate more or less free of legislative control. There seems to be no reason why an effective oversight mechanism should not co-exist with a vigorous approach to improved standards of health and nth and nutrition: the point is to be clear exactly what the committees charged with oversight should be trying to achieve. Are they working to ensure conformity with the national law? Or are they attempting to monitor and contain the activities of commercial operators? Are they merely satisfying the desire for information, and if so, are they serving the scientists or the general public?

The answers to these questions will largely be determined by the sanctions that they can apply. The national law may prescribe penalties such as fines for scientists who fail to notify the appropriate committee of their activities or who flout the committee's requirements - including where appropriate the need for continued monitoring after the end of an experiment. There may also be civil sanctions where the law allows an aggrieved party to sue for damages in the event of an accident especially where workers have ignored specialist advice. Research institutes relying on public or private funding are in general highleral highly sensitive to a threatened loss of research funding or the closure of a laboratory. An analogous sanction for a commercial operator would be the possible loss of company profits as a result of a fall in public esteem.

Where countries have little or no provision for a nationally-authorized committee structure, scientists with a sense of public concern still have the option of setting up an appraisal mechanism at a local level, even if only to be able to inform their own community of the hazards to which they might be exposed.

Sources of Guidance for Committees

If the role of a local committee is to give guidance to a prospective experimenter who submits a project for its opinion the committee itself must know where to find the information on which to base its judgements knowing that these will be defensible. A national committee may be in the same position when faced with a novel and potentially controversial proposal.

For both

For both types of committee the first consideration must be the national law of the country. In the United Kingdom the relevant legislation (much of it codified in the Health & Safety at Work (1974) Act and in subsequent law on the environment) is rendered more accessible to the working scientist in the form of Notes of Guidance, fairly frequently updated, which themselves are sometimes further explained in Newsletters from the specialist national committees ACGM and ACRE.

Beyond the level of national frameworks lies that of international codes which may contain helpful advice to countries seeking to set up national mechanisms but, in the absence of the binding force of an international convention, are not formal prescriptions. The demand for these has come from individual countries where there are concerns that pressures for releases and other work with GMOs may lead to uneven standards and thence to exploitation of countries that are perceived rightly or wrongly as having little control. Buontrol. But the demand has also come from some biotechnology companies themselves who in turn are concerned that if they work in an unregulated part of the world they may be seen as contemptuous of environmental concerns, and thus suffer from at the least a loss of public esteem and perhaps ultimately heavy civil penalties. The UN system is seen as having a special role here, being regarded as neutral in the potential for conflict between countries: although the UN agency structure has been criticized as providing opportunities for wasteful competition in the provision of advice it has over the years harnessed the services of a wide range of specialists. Among its achievements are the Convention on Biodiversity and the Voluntary International Code of Conduct (VICOC) for the Release of Organisms into the Environment in 1991 which stipulated that member countries need:

It is perhaps a measure of the progress that has been made in the past six years that such statements can now seem self-evident (with the exception of the last - the "education" of public opinion must at the least be balanced by a willingness to attend to that opinion when expressed: see below).

Two aspects of VICOC have had enduring usefulness. First, it listed as an appendix the authoritative statutes and guidelines operating in several different countries; this list is now seriously out of date and a new version would be of great value. Second, it recommended the establishment of an international Biosafety Information Network and Advisory Service (BINAS), which has since been set up by the International Centre for Genetic Engineering and Biotechnology (ICGEBnology (ICGEB) to provide support through links in key centres (DETAILS.....). The real importance of international support mechanisms may lie in the facilitation of regional co-operation between countries with shared problems and in the discovery of mechanisms for addressing the problems that arise when organisms released in one country are found to have undesirable characteristics on spreading to another with a different climate.

The international community has also been active in providing training courses for those with biosafety interests such as the annual meetings sponsored by ICGEB in Trieste, Italy, since1991. Several organisations have participated in arranging similar courses in response to local demand in various countries. In parallel to such courses are guides such as the present volume which has been constructed to allow for updating of individual sections as the need arises.

It has been stressed that many of the problems in biosafety risk assessment spring from the novelty of novelty of the work involved, but the existence of a corpus of knowledge that has built up over twenty years has allowed the construction of databases. These are now being actively developed, and permit the observer not only to find out the conditions under a which a proposal with similarities to one now contemplated has been carried out successfully, but also to see where there have been breakdowns and hence lessons that must be learnt. Hence the information network run by IRRO and the OECD database.....(more examples here). Links to many of these systems are now accessible on the World Wide Web: see for instance the UK Department of the Environment home page at:

At a more simple level there are listings e.g. of pathogenic bacteria with recommendations for containment of individual species (see ACDP.....).

Finally, some organizations (e.g. SEI) have set up panels of experts whose members can be made available on rvailable on request. Those of SEI are at present available only to individual governments. As in all situations that ultimately reply, however, on the deliberations of groups of individuals, the committee members will have to exercise their own judgements when weighing the possible costs and benefits of proposed releases for their own communities.

The Role of Public Opinion

The public is inescapably involved in biosafety risk appraisal. Members of public interest groups may sometimes be members of national or local committees and may be answerable to local communities, labour organizations, or bodies with a special interest in e.g. environmental issues. More generally the public at large may control through its political representatives the funding of basic science and, through the market place, the likelihood of commercial developments flowing from biotechnological advances. There is hence a twofold need: to ensure that the public is meaningfully informed of the nature and pture and possible consequences of biotechnology, and to be able to ascertain and act on public concerns. The language in which public involvement is discussed can distort thinking in this area. M. Leopold (CAB Guide p.8) has stressed how the impact of public perceptions on commercial biotechnology cannot be gauged purely scientifically since the perceptions may be founded on considerations that are scientifically unsound or are unrelated to science itself. Hence the notion of "educating the public", which will have patronizing overtones for some readers, may founder if the nature of public concern is not fully understood, and may become meaningless where the public in question sees an ethical principle at stake. Likewise the notion of "legitimate public concern" raises the question of what is legitimate. Yet biotechnologists can point to the Asilomar moratorium (see above) as indicating a concern among pioneering scientists, perhaps unique, about the social consequences of their work. The so-called Eurobaromeurobarometer surveys (1991 and 1993) indicate that those Europeans who believe that biotechnology makes a positive contribution to life is around 50%, although within this figure there are sharp differences between different EU countries. These same surveys, however, showed that most respondents answered incorrectly one or more questions designed to be value-free (e.g. "Are there test tube babies which develop entirely outside the mother's body?"). A similar lack of understanding is shown by a US sample questioned about clinical trials (Nature 30.5.96): almost half thought that the reason for keeping a group of subjects as controls in a drug trial was to save them from the risk of being poisoned. Leopold (op. cit.) distinguishes three types of public audience:

It is this last group that is most likely to be reached by "educational" initiatives designed to inform opinion. In countries with a high level of general education and a strong democratic tradition, this group will not only be large but is most likely to be represented on decision-making bodies. As suggested by the EU findings, however, the widely differing views on biotechnology taken by countries with similar levels of public awareness indicates that the debate is a real one and that it is misleading to search for a "right" answer. The dilemma has led to fluctuations in time in the levels of regulation imposed by governments: at its extremeits extreme is the view that there is no necessity to conduct risk assessment experiments to ensure confidence about field testing of new plant varieties (see discussion in BINAS News Vol. 2, issue 2, 1996).

Whatever the prevailing public attitude, it is certain that risk assessment deliberations that are seen as secretive (or worse, scientists who neglect to inform biosafety committees of their proposed work or who ignore the advice given them) will result in damage to public relations. Some regulations require that notice of a field trial be given in prescribed form in the local press, and a climate of good relations with the media generally is often seen as worth the time and effort involved.