Abstract
A workshop was held in Dublin on Comparative Radiobiology and Protection of the Environment last October. The workshop was organised by the Radiation and Environmental Science Centre at the Dublin Institute of Technology (DIT) in collaboration with the Radiological Protection Institute of Ireland (RPII). The international programme committee consisted of Dennis Woodhead, CEFAS, Jack Valentin, ICRP, Werner Mueller, University of Mainz, Frank Turvey, ex RPII and currently a consultant at DIT, David Sowby, retired ICRP, and Carmel Mothersill, DIT. The workshop had three stated aims:
1. To discuss the state of our knowledge about radiation effects in wild species of plants and animals.
2. To consider universal mechanistic endpoints which could allow the establishment of a `sensitivity scale'.
3. To develop a framework for radiation protection of species other than man.
The workshop theme was prompted by recent concerns that standards of radiological protection designed to protect man can not always be assumed to protect other species. It was also prompted by concern arising from recent paradigm shifts in our thinking about mechanisms of low-dose effects. Cellular stress due to reactive oxygen species generated by many toxic chemicals and radiation is now known to be an important effector of biological response to environmental conditions. This means that mixed exposures to chronic low levels of a variety of pollutants, including low levels of radionuclides, may have consequences which are unpredictable from consideration of the effects of the radiation dose alone.
Questions regarding how we consider species other than man involve not only science but ethics and law, so the workshop organisers invited participation from people with a very broad spectrum of expertise to address defined questions in these areas. The aim was to generate discussion between microbiologists, ecotoxicologists, molecular and cellular biologists and developmental biologists on the one hand, and regulators or those who provide advice to regulators concerning protection standards on the other.
The workshop opened with formal presentations from Lars-Erik Holm representing the International Commission on Radiological Protection (ICRP) and Carol Robinson representing the International Atomic Energy Agency (IAEA). Both speakers outlined the policy of their organisations in relation to protection of the environment. Dr Holm said that the area was in the process of being developed by ICRP and that they had established a task group to help formulate a way forward. He identified a number of areas in need of further clarification: the basic criteria for protection; the inclusion of protection of the environment as an objective of radiation protection; identification of the level of differentiation of species, endangered populations, etc, of concern. He also highlighted the need for an examination of alternative criteria for protection and for the provision of guidance in relation to potential exposure situations, the clean-up of contaminated areas and intervention. Carol Robinson summarised the work of IAEA, which aims to provide a regular forum to promote international information exchange on the subject of environmental protection from the effects of ionising radiation, and is working towards the development of relevant guidance on protection standards. IAEA ran an international specialists meeting in Vienna (29 August-1 September 2000), which provided an opportunity for information exchange, regarding appropriate regulatory and research developments. It also provided a platform for detailed discussion of many of the issues that would need to be addressed in developing a system for protection of the environment from the effects of ionising radiation. The specialist's meeting made significant progress in developing an international consensus on the general objectives of environmental protection and the meaning of harm in this context. The main focus of the meeting was the use of available information to form the basis of a practical policy for protection, rather than a detailed debate of the science of comparative radiobiology.
After the formal presentations, the rest of the workshop was structured around questions. These were addressed by two or three discussion leaders who managed an open discussion.
1. What do we know about comparative radiation biology of species other than man?
Discussion leaders: Rinchevitch, Shima, Mothersill The main points raised during the discussion follow. Woodhead, Pentreath, Mueller, Rinchivitch, Mothersill, Osborne and many others have experimental laboratory and field data. The problem with most of the laboratory data is that it is concerned with high acute doses which are not at all relevant to the situation in the environment. Carmel Mothersill has recently completed a survey of the literature concerning laboratory data and concluded that the data are mostly from the literature pre-1970. This was when there were no molecular biological tools to assess effects and when cell and tissue culture was in its infancy. Therefore the data relate to endpoints such as `death post 20 Gy acute dose', etc! The reason the area has been neglected since the 1970s is not clear, but funding for work on species other than man appears to be a major problem, unless relevance to human health or well being can be shown. Also, the need to use high doses, and the crudity of the endpoints, made the experiments particularly difficult to do. Woodhead suggested that the interpretation of the results of laboratory studies, in an environmental context, was problematic: in many cases the organisms used in the studies are precisely those that are adaptable (or insensitive) to environmental change, and some studies have shown that animals are more resistant to the effects of radiation in a `protected' laboratory situation than in their naturally stressful native habitat. He stressed the need to study animals/plants in the field under relevant exposure conditions. In particular it is important to study not only dose rate to tissues but effects where other environmental stressors are additionally present. The biologists pointed out that most of the studies at low doses and dose rates in the laboratory were negative. Equally difficult to obtain were positive laboratory data for mixed exposure situations at relevant exposure levels. Hence the need to use high doses to get a publishable result. The consensus was that we know rather little about comparative radiobiology at relevant doses and dose rates, and urgently need to research this.
2. What are the universal mechanisms determining radiation response which could be compared between species to give a `scale of sensitivity'?
Discussion leaders: Wright, Boreham, Mueller, Copplestone This question was concerned with how we might monitor effects of low doses of radiation, given that at the relevant doses and in the relevant habitats we are actually dealing with chemical, physical and biological factors which all contribute to the survival of the individual and the health of the species, population and habitat. Should we look for responses which are common indicators of stress? Should we try to identify sentinal species? How do we factor in natural adaptation?
The discussion ranged from detailed considerations of universal mechanisms such as genomic instability and heat-shock protein responses, to tongue-in-cheek suggestions that if man were removed from the environment, everything else got along just fine. A number of biologial endpoints which might be useful were presented by Mueller (immune responses and apoptosis genes in lower invertebrates), Wright (genomic instability and oxidative stress responses), Ulsh (chromosome translocations in turtles), Billinghurst (coral bleaching), and Austin and Mothersill (cellular pathology in crustaceans). These endpoints have all been tested in wild species using a variety of in vivo and in vitro laboratory experiments. They have all been shown to change at relatively low radiation doses (0.01-0.5 Gy or 10-500 mSv) and, most importantly, they all respond to a variety of chemical and physical agents including UV and heavy metals, thus offering the possibility of establishing a universal damage burden index. This could be, for example, the total mutation burden in a critical ubiquitous gene such as p53, or measurement of reactive oxygen species, which would indicate oxidative stress. The biologists in the group were keen to point out that having a useful bio-marker was no use unless the critical animals and plants in the habitat could be identified and the bio-marker response related to some measure of `harm' at the individual or higher level of biological organisation. There is no possibility of monitoring every species (the idea of worms wearing dosimeters raised some laughter), and even within species in wild populations, the issue of individual variation due to genetic variation confounds the results. Some biologists in the group favoured approaches based on biodiversity measurements rather than molecular endpoints, but again the argument was that biodiversity is far more likely to be adversely affected by the mere presence of man, and his sequestration of habitat for his own use, than by the doses of radiation that are likely to occur in the environment as a consequence of human activity.
The consensus here was that molecular bio-marker approaches were unlikely to provide the basis of a protection system at present since both regulators and operators would need to be able to predict the effect of particular operations in order either to regulate them or to ensure compliance. Laboratory investigations of the mechanisms of low dose rate radiation effects in species thought to be critical/sensitive/sentinal could, however, provide useful information for the future refinement of dose-rate criteria for protection derived from the currently available information.
3. How can we relate field and laboratory studies?
Discussion leaders: Woodhead D, Woodhead A, Lyons, Billinghurst This session was led by the field biologists/radiation ecologists in the group. Ecological endpoints such as species diversity, defining and monitoring of sentinal species, in vivo/in vitro bridging systems, reproductive effects and population dynamics were discussed. The major problem was again identified as the lack of laboratory data at relevant doses and dose rates. This means that existing data are not relevant for validation purposes. That is, they cannot tell us whether a particular biological effect in the field could have been caused by radiation exposure. There was considerable discussion on how relevant laboratory experiments might be done. Any handling or intervention was seen by some field biologists to invalidate any results obtained. Removing predator stress or competition for food and mates was also seen as invalidating any laboratory data based on tissue responses to experimental radiation exposure. The available data, while not directly transferable to an assessment of effects in a contaminated environment, do indicate that the resulting chronic (i.e. over the life-time), low dose rate environmental exposure could produce deterministic (e.g. reductions in fertility and/or fecundity) or stochastic (e.g. germ cell mutations) effects of varying degree in a proportion of the individuals in the (undefined) population. The problem is to interpret these possible responses in terms of some measure of `harm' to the environment. They also saw radiation very much in the context of other chemical, physical and biological stresses experienced by wild populations.
The consensus was that few relevant laboratory studies exist which can validate field studies and that the way to do relevant laboratory studies is far from clear. The conclusion that laboratory studies should attempt to address the mechanisms, and consequences, of chronic, low dose rate radiation exposure in a manner that informs the regulatory process, was reiterated.
4. What are the issues for protection legislation?
Discussion leaders: Turvey, Austin, Osborne, Rafferty This session was divided into two parts. The first part discussed the issues from the perspective of the regulator and the second from the perspective of the biologist. Among the issues covered were: approaches to protective legislation, what to protect? Problem of identifying sentinal species, problem of biodiversity, problems of mixed low-level exposures and stresses, individual versus population protection. What do we mean by, and require of, measures for environmental protection in the context of increased radiation exposure? What are the dose rates that already exist, or are likely to arise in contaminated environments?
Frank Turvey and Richard Osborne identified the practical problems involved in developing a workable system of protection. Brian Austin and Barbara Rafferty led the discussion from the standpoint of the biologist. A number of questions considered had an ethical dimension which is returned to below. The discussion considered whether all species and habitats should be protected, or only those which were deemed to be of value to man or where damage might subsequently pose a hazard to human health. The point was raised that there might be little sympathy for protecting intestinal bacteria from the harmful effects of abdominal x-rays to their host. While this is an extreme (and extremely unrealistic) example, it does make the point that choices have to be made to define protection standards that do not prevent beneficial uses of radiation. Furthermore these questions highlight fundamental issues such as: what is really meant by the term `environment'?; how do we define environmental `harm'?; and, is the ultimate motivation for environmental protection the protection of man or the environment, or elements of the environment, or, indeed, all three?
The idea was discussed that an arbitrary dose limit of, for example, X times the natural background might be the only feasible option. This would overcome problems associated with local differences in natural background and would avoid consideration of individual species within a habitat. The `regulator's' view was that a dose limit of some sort had to be defined, which would satisfy those concerned about the possible effects on species other than man that adequate protection was in place, but would also allow hospitals and industries to function. The use of dose rate values presented in IAEA TRS 332 and in an UNSCEAR review, which represent levels below which there is no evidence, from the available information, to indicate radiation-induced damage on populations, were suggested for use as upper-bound values. It was suggested that this approach could be reviewed and revised as additional information became available. Many of the biologists in the group challenged this, pointing out that the basis of our current dose limits for man is probably flawed. Frank Turvey supported the adoption of the primary and secondary standards already proposed by the IAEA. These could be adjusted in the light of studies on flora and fauna exposed to high doses of anthropogenic radiation in areas like Kysthym, Chelyabinsk or the 30 km radius exclusion zone around Chernobyl - field laboratories in fact. He warned against giving undue priority to protection against radiation at the expense of protection against other more dangerous and more obvious threats to our environment. A very heated discussion followed and the group had to agree to differ on the relevance of the basis of our current system of assessing likely risk to humans. Very little reliable information is available about low-dose chronic effects, except from the sites listed above, where dose/dose rates and pre-existing health status of both man and the environment are unknown variables. The basis of the LNT extrapolation from high to environmentally relevant low doses was also challenged. It was pointed out that epidemiology cannot address the low-dose region of the dose response curve in real situations, where exposures to many other pollutants and biologically relevant factors creates a high background. New mechanisms, such as genomic instability, adaptive responses and cell communication based bystander effects, all cast doubt on the legitimacy of extrapolating from high to low doses, although how they might affect the low-dose region of the dose response curve is not clear. This conclusion led to discussion of whether we need to consider stochastic effects at all when discussing protection of the environment. Several people said that for wild species, we can not legislate for individuals and have to consider the health of the population. This probably means reproductive health of the breeding group and has to be considered as a non-stochastic effect.
The consensus (which was not unanimous) was that probably all we can do is impose a limit of some sort and continually reconsider it as new information becomes available. Professor Bo Lindell, who was an invited keynote lecturer at the workshop, made clear that this was how human radiation protection evolved from crude first principles to its present level of sophistication.
5. What ethical dimensions are there?
Discussion leaders: Lindell, Seymour and Persson The discussion here considered why we want to protect species other than man, how we select species to protect (benefit to man, cuddly animals, etc) and whether life centred or human centred world views were relevant to our debate. The problem of how to assign `rights' to species which could not enforce those rights was highlighted. Discussion also took place on the practical problem of defining `harm'. The key role of humans in habitat destruction and forcing extinction of wild species was raised.
Persson pointed out that as the most evolved and intelligent life form, it has always been argued from religious grounds, which are usually interchangeable with ethical grounds, that man has a duty to act as a responsible custodian of the environment. Seymour pointed out that a non-anthropocentric viewpoint was not possible, unless one could enter a mystical or mental state where one's own sense of self disappeared. Whilst this state is achievable, it is not achievable by the majority of people (and probably not desired). It is therefore logically inconsistent to try to base regulations and species protection on anything other than an anthropocentric point of view, and man should therefore base regulations on the responsible custodian principle long advocated by most religious and ethical groups. Several of the participants disagreed with this view in principle, saying that a world view which does not place man as custodian or servant, but as an integral part of the environment, must be accommodatable within a protection framework. Most participants however, accepted that any system of protection would necessarily be based on man's viewpoint of the `rights' of other species, since only man could enforce those rights, but there were a number of interpretations of the extent to which this statement implied that such views would necessarily be anthropocentric.
The consensus, which was unpalatable to many delegates, was that any system of protection of species other than man, must be enforced by man and therefore will reflect man's interests (although not necessarily as a primary focus of decisions, for example, of which species to protect or not protect). The workshop agreed to a consensus statement which reads as follows:
Radiation is but one of many stressors of life and our knowledge of the interactions is limited. This workshop concludes that given the present state of our knowledge about radiobiology, a pragmatic approach to regulate radiation exposures to non-human species would be to make use of dose rate values that are unlikely to cause stochastic or deterministic harm in individuals that will become apparent at the population level. We realise that this may not protect against all possible latent harm in the current and future generations, habitats or species. Furthermore we understand that other stressors may modify the effects of radiation exposure. We recommend a multidisciplinary approach to improve the scientific basis for regulation. High priority areas include experimental (1) and conceptual (2) considerations.
1. Experimental considerations:
(i) experiments with environmentally relevant dose rates and radionuclides
(ii) trans-generational exposure.
2. Conceptual considerations:
(i) development of protocols for mixed exposures
(ii) identification of sentinel species
(iii) biomarkers as indicators of exposure
(iv) biomarkers as indicators of possible harm.
Co-ordinated work in these areas will improve the scientific basis for the development of a regulatory framework.
Acknowledgments I wish to thank Carol Robinson and Denis Woodhead for their considerable help in writing this report.