RRS

COMARE Statement on Radiobiology Research in the UK

In 2007, the committee was asked by the Department of Health to establish the current status of radiobiology research in the UK and advise all interested parties on the concerns raised and the recommended actions.

The Radiobiology Research Subgroup (RRS) was formed by COMARE to lead discussions with the major funding bodies on identified issues.

What areas of radiobiology research are currently being funded?
What areas of radiobiology research are the funding bodies prepared to support?
What training is available for young scientists in radiobiology?

Discussions were held with representatives from the Department of Health (DH), the Medical Research Council (MRC), Cancer Research UK (CRUK), the National Cancer Research Institute (NCRI), the Health Protection Agency (HPA) and Children with Leukaemia.

Background

The Department of Health runs a Radiation Protection Research (RPR) Programme on a three year cycle and on a budget of ~£1.2 million per year. It has a specific research strategy for the programme, which is updated every three years to incorporate current areas of radiological protection, both for ionising and non-ionising radiation. Due to the budget constraints there is a limit to the number of projects funded. COMARE’s work programme includes an involvement in the review of the RPR Programme, which maintains the committee’s vested interest in the field of radiobiology research.

The Oxford Initiative of Radiation Oncology and Biology has been established within the University of Oxford bringing together researchers from the Gray Cancer Institute, Northwood and the MRC Radiation and Genome Stability Unit, Harwell with Oxford based researchers. The unit is collaboratively supported by CRUK and the MRC, and is directed by Professor Gillies McKenna, who has been appointed Chair of Radiation Oncology and Biology. Professor McKenna advised COMARE that the Oxford Initiative would not be able to cover all areas of radiobiological research and that the main focus would be on translational radiobiology. The formation of the Initiative was supported by COMARE; however it was recognised that not all of the research groups associated with the original institutes could be located in the new unit. This has lead to the establishment of research groups in Queen’s University, Belfast and Oxford Brookes University, with an associated Chair of Radiation Biology at Oxford Brookes.

While strongly supporting the Oxford Initiative, COMARE has expressed concerns that the present funding initiatives leave voids in areas of basic and applied radiobiology funding. At present, research priorities of funding bodies appear to focus on translational radiobiology and radiotherapy. COMARE recognises that basic radiobiological research underlies and supports both radiation protection issues and translational radiobiology and appreciates the importance of sustaining research this field. Although the establishment of the Oxford Initiative is welcomed, it is clearly not able to address the lack of research in areas of basic and applied radiobiology and radiation protection. In fact, the establishment of the Initiative resulted in the absence of a number of longstanding project holders in the current DH RPR programme through a freeze on external funding applications.

In preparation of this work the subgroup produced a list of radiobiology research topics requiring attention (see appendix A). This list is similar to the priority research areas for radiological- and nuclear-threat countermeasures published by the U.S. Radiological/Nuclear Threat Countermeasures Working Group in 2005 (Pellmar et al, 2005). The highlighted research areas covered radiation injury, radiation protection, biomarkers, and the effects of both low and high dose radiation and predominantly related to ionising radiation. However concerns over non-ionising radiation research, such as ultrasound, were also recognised. The COMARE list was also endorsed by the Advisory Group on Ionising Radiation (AGIR) through the work of the High Dose Radiation Effects and Tissue Injury subgroup.

Funding Information

The major funding bodies for radiobiology research are CRUK, the MRC and DH. The MRC’s Molecular and Cellular Medicine Board includes radiobiology under their strategic priorities for cancer research; however unlike DH’s RPR Programme, this is not subdivided into specific priority areas.

NCRI is a partnership between the government, charity and industry which promotes co-operation among the 21 member organisations for the benefit of patients, the public and the scientific community. It undertakes analyses of what research is being undertaken and maintains a Cancer Research Database, containing details of funded projects submitted by the NCRI partners.

At the first meeting of the subgroup with the funding parties, it was apparent that there was little communication between the parties with regards to radiobiology funding. It was determined that, although eligible, the DH RPR programme had not been included in the NCRI database.

The subgroup undertook an analysis of the NCRI database for all projects active in 2007, including the DH RPR Programme, to establish those relevant to radiobiology and radiotherapy. The database was filtered using selected search terms and the extracted projects classified according in 15 categories based on the area of research (see Appendix B). Twenty-two projects out of 227 selected projects were allocated to more than one category.

In 2007 the total amount spent on cancer research was over £390 million, according to the NCRI database. The amount allocated to radiobiology or radiotherapy projects was just over £20 million. The largest category was found to be ‘Therapy – clinical trials’, with 72 associated projects and 28% of the allocated funds. CRUK were the major funders in the analysis with 138 of the 227 projects. The Department of Health funded 46 projects with 17 from the RPR Programme. Although the MRC did not invest in the greatest number of projects, it did include a large investment into the Oxford Initiative in 2007.

No projects funded in 2007 investigated the acute effects of ionising radiation and only 0.2% of the projects were related to radiation protection. The analysis confirmed the concerns that there were significant voids in basic and applied radiobiology research at all levels (molecular, cellular and tissue). The DH RPR Programme provides significant coverage of the research areas of concern but with restricted resources it is limited as to what can be funded. Representatives from both MRC and CRUK confirmed that applications would be considered on all of the topics listed by COMARE, although the level of priority associated could vary greatly. Each application would be dealt with on a case by case basis. COMARE expressed concern over the priority being awarded to radiobiology topics by funding bodies and wished to raise awareness of those research areas not currently funded.

Support

The Academic Clinical Oncology and Radiobiology Research Network (ACORRN) launched in 2005 to provide networking and support facilities for researchers into radiotherapy and radiobiology in the UK. The ACORRN radiobiology working group is trying to establish a database on UK researchers in radiobiology, noting who was funding them and what was being funded. It is unclear whether the resources will be available for this work to be completed. COMARE considers that if this project remains unfinished, it will be a serious waste of time and resources from current radiobiologists already active in the field.

Training Initiatives

It is evident that the research base able to carry out basic research biology is small and therefore it is important that there is an enhancement of training in the radiological sciences and the possibility of maintaining that expertise in the UK.

The European Radiation Biology MSc postgraduate course on the radiological basis of radiation protection results from a collaboration between five universities in five Member States (Trott et al, 1998). The twelve month MSc course in Radiation Biology is currently co-ordinated by the Department of Oncology, University College London (UCL). Approximately 140 students have successfully completed the course since 1992, although only 16 students came from the UK. Each year between 7 and 12 students are accepted onto the course. Cancer Research UK provides a small number of bursaries for this course.

The Oxford Initiative currently offers a Graduate Research Training Programme, leading to the award of a DPhil from the University of Oxford. It comprises of a taught course in Radiation Oncology and Biology and at-the-bench research training. At present two three year posts are funded by CRUK with further two posts for five years being funded by the MRC. Approximately 50% of applicants in the last two years have been from overseas.

In conjunction with its Graduate Research Training Programme, the Oxford Initiative is in the process of establishing an MSc course in Radiation Biology, with an estimated start date of 2009.

Recommendations

1. Funding bodies should be made aware of priority areas for radiobiology research that are not currently being funded and should be encouraged to increase resources in these fields.

Research into acute effects of ionising radiation.
Research into radiation injury and radiation protection.
Basic and applied radiobiology research at all levels – molecular, cellular and tissue.

2. DH RPR Programme should have increased funding available to facilitate the return of projects lost during the establishment of the Oxford Initiative and to ensure coverage of research areas not supported by other funding bodies.

3. The various funding bodies should give serious consideration to the provision of the small amount of resources which would allow the completion of the UK database of radiobiology researchers by the ACORRN radiobiology working group. Ideally this would lead to a network based service being made available for radiobiologists to facilitate discussions and provide a system for disseminating information. Furthermore the original plan of the ACORRN radiobiology working group included facilitating a workshop organised for radiobiologists and funders to meet and discuss priority research issues in the field of radiobiology.

4. We recommend that representatives of the funding bodies agree to meet to discuss priority research topics. The fact that the DH RPR programme did not appear on the NRCI database is suggestive that communication between funding bodies has deteriorated in recent years. Ideally this meeting would occur on a regular basis and would include representation by the COMARE secretariat to preserve COMARE’s interest in this issue.

5. Increased training should be available in the UK for radiobiologists, with improved provision of a career pathway on completion of the studies.

6. In this statement we have focused mainly on ionising radiation research. However, we wish to express concern about the lack of information underpinning new diagnostic and treatment techniques available using non-ionising radiation, for example, Magnetic Resonance Imaging/Spectroscopy (MRI/MRS) and High Intensity Focused Ultrasound (HIFU). There is very little research into either the early or late effects of exposure at these new high intensities and we recommend that applications for appropriate peer reviewed studies be included in the portfolio of the bodies which fund radiobiological research.

Appendix A:

Determination of the mechanisms of radiation injury at the molecular, cellular, tissue and organ levels.
Research into the mechanisms of radiation carcinogenesis with reference to individual susceptibility and gene-environment interactions).
Development of animal models for the assessment of radiation injury and the evaluation of methods for treating such injuries.
Research into the effects of internalised radiation emitters (both at clinical and environmental levels).
Development of radioprotectors (for use prior to exposure) and therapeutic agents post exposure.
Development of novel approaches for radioprotection and/or treatment of radiation damage using progenitor cells, cytokines, growth factors and stem cell biology.
Antimicrobial therapy for infections associated with radiation exposure.
Development of biomarkers and automated biodosimetric assays.
Determination of the mechanisms of radiation-induced injury which lead to the development of cancer and the possible interactions with other carcinogenic agents.
Studies of long term health effects of radiation exposure by following the health of irradiated individuals.
Determination of the impact of low dose radiation exposure including that received from CT scanning on cancer induction.
Research into treatment modalities for exposure to high dose radiation from both external and internal sources.
Explore the consequences of combined injury from radiation and other sources (both physical and chemical).
Development of approaches for understanding and mitigating the psychological impact of radiation exposure.
Resources should be available to allow radiobiology research groups in the UK to forge links with centres carrying out research into DNA repair mechanisms and also to forge similar links with the Chernobyl Tissue Bank.

Appendix B:

Category 1: Basic Science

Category 2: Genetics

Category 3: DNA Damage and Repair

Category 4: Therapy - clinical trial

Category 5: Therapy – preclinical

Category 6: Therapy - development and mechanisms.

Category 7: Therapy - prediction/prognosis

Category 8: Diagnosis and Imaging (of tumours)

Category 9: Normal tissues - clinical studies

Category 10: Normal tissues - preclinical/mechanisms

Category 11: Protection

Category 12: Risk/Epidemiology

Category 13: ACORRN

Category 14: Radiation/Cancer Biology

Category 15: Education

References:

Pellmar TC et al (2005). Priority list of research areas for radiological nuclear threat countermeasures. Radiation Research, 163 (1), 115-123.

Trott KR et al (1998). Postgraduate studies in radiation biology in Europe. Radiation and Environmental Biophysics, 37 (3), 139-142.

17 November 2008