- Email: [email protected]
UK Biobank: bank on it
Comment
tool. Scale-up of such implementation efforts would also include increased efforts to bundle community-directed treatment with ivermectin with preventive chemotherapy treatments for other high-prevalence neglected tropical diseases.9 However, when possible, monitoring and evaluation of both community-directed and integrated control programmes for neglected tropical disease should include best-practice efforts to detect the emergence of anthelmintic drug-resistance. Simultaneously, we need to anticipate the possibility of further ivermectin resistance and greatly increase our current level of effort and support to develop and test a new generation of control tools for onchocerciasis. Such tools would include better diagnostics, alternative microfilaricides such as moxidectin, and innovative anti-Wolbachia therapies.2,10 The development of a new-generation macrofilaricide for O volvulus continues to be an elusive goal, but remains a high priority. As an alternative but complementary approach, we now have several promising Onchocerca vaccine antigens and the proof of concept that protection against onchocerciasis can be experimentally induced.11–13 Many of the O volvulus antigens are orthologues of other helminth vaccine antigens currently under development.13 We therefore need to look at strategies by which a new generation of vaccines against O volvulus could be developed and linked with community-directed treatment with ivermectin in a programme of vaccine-linked chemotherapy.13 Now is the time for global health leaders to build on the strengths of community-directed treatment with ivermectin, and advocate and support
the development, testing, and distribution of a new generation of onchocerciasis-control tools. Peter J Hotez Sabin Vaccine Institute and Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC 20037, USA [email protected] I declare that I have no conflict of interest. 1
2 3
4
5 6
7
8 9
10 11
12 13
Levine R and the What Works Working Group. Case 6, controlling onchocerciasis in Sub-Saharan Africa. In: Millions saved, proven successes in global health. Washington DC: Center for Global Development, 2004: 57–64. Basanez MG, Pion SDS, Churcher TS, Breitling LP, Little MP, Boussinesq M. River blindness: a success story under threat. PLoS Med 2006; 3: e371. Amazigo UV, Brieger WR, Katabarwa M, et al. The challenges of community-directed treatment with ivermectin (CDTI) within the African Programme for Onchocerciasis Control (APOC). Ann Trop Med Parasitol 2002; 96 (suppl 1): S41–58. Seketeli A, Adeoye G, Eyamba A, et al. The achievements and challenges of the African Programme for Onchocerciasis Control (APOC). Ann Trop Med Parasitol 2002; 96 (suppl 1): S15–18. Boatin BA, Richards FO Jr. Control of onchocerciasis. Adv Parasitol 2006; 61: 349–94. Osei-Atweneboana MY, Eng JKL, Boakye DA, Gyapong JO, Prichard RK. Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in endemic communities in Ghana: a two phase epidemiological study. Lancet 2007; 369: 2021–29. Eng JK, Blackhall WJ, Osei-Atweneboana MY, et al. Ivermectin selection on β-tubulin: evidence in Onchocerca volvulus and Haemonchus contortus. Molec Biochem Parasitol 2006; 150: 229–35. Hotez PJ. The National Institutes of Health roadmap and the developing world. J Invest Med 2004; 52: 246–47. Molyneux DH, Hotez PJ, Fenwick A. “Rapid-impact interventions”: how a policy of integrated control for Africa’s neglected tropical diseases could benefit the poor. PLoS Med 2005; 2: e336. Taylor MJ, Bandi C, Hoerauf A. Wolbachia bacterial endosymbionts of filarial nematodes. Adv Parasitol 2005; 60: 245–84. Lustigman S, James ER, Tawe W, Abraham D. Towards a recombinant antigen vaccine against Onchocerca volvulus. Trends Parasitol 2002; 18: 135–41. Nutman TB. Future directions for vaccine-related onchocerciasis research. Trends Parasitol 2002; 18: 237–39. Hotez PJ, Ferris MT. The antipoverty vaccines. Vaccine 2006; 24: 5787–99.
UK Biobank: bank on it See Editorial page 1974
1980
The UK Biobank1 aims to include 500 000 people from the UK who are aged 40–69 years.2 The project will involve baseline questionnaires and physical measures (eg, standard anthropometry and spirometry), and will store blood and urine samples. The strategy is to collect baseline data on a large general population sample, to obtain broad consent from participants for unspecified health research, and to follow up the participants through linked population-level UK medical and other health-related records so that nested case-control studies of a wide range of common adult diseases can be investigated. The longterm goal is to explore the aetiology of common complex
diseases by investigation of their association with underlying genetic and lifestyle determinants. Samplesize calculations indicate that, with realistic assumptions, UK Biobank will be sufficiently powered to detect a main-effect odds ratio of 1·3 or higher after 6 years of incident-case collection for type 2 diabetes, after 8 years for diseases with an incidence profile similar to coronary heart disease, and close to 20 years for diseases with an incidence profile similar to stroke, Alzheimer’s disease, and breast or prostate cancer.3 An integrated pilot study took place for the UK Biobank between February and June, 2006. The aim www.thelancet.com Vol 369 June 16, 2007
Comment
was to test the recruitment process at the throughput required for the main phase. Around 3800 participants (about a tenth of those asked) attended the single pilot centre. Although the overall response rate is cause for some concern, the pilot was judged a success. The low response rate will probably follow through to the main study and means that the UK Biobank will clearly never be fully representative of the UK population. Such under-representation will not matter for many of the project’s aims. The main study is now fully funded (£59 million), began in February, 2007, and will finish in 2010. A large population-based cohort by itself does not guarantee success in aetiological studies of complex diseases, and the UK Biobank and other similar projects have been criticised.4 Objections include: that specific disease-focused case-control studies would be more efficient; only limited deep phenotyping (objective physiological measures) is being done; the age-range is not representative of the general population and many of the relevant exposures will have occurred previously; and that the projected time-lines to develop sample sizes of incident cases with sufficient power to detect realistic effect sizes are too long (at least 10 years for most diseases). The study is also predicated on the common-disease common-variant hypothesis. All these objections have some validity, although they also involve substantial subjectivity. An important lesson from the past decade of complex-disease genetic epidemiology is that there is no one model for gene discovery, study design, or analytic approach that will be the best in all situations. Both case-control and cohort designs are likely to be necessary,5,6 (especially in the context of gene–environment interaction6 and Mendelian randomisation approaches7,8). The UK Biobank now seems to represent an optimised solution for its funding and target sample size. However, the overall value of the study would be greatly enhanced with more detailed physiological phenotyping on all or some of the participants. There is growing evidence that the correlation between objective measures and questionnaire data for key indices (eg, physical activity) can be poor and lead to misleading conclusions if only the self-reported data are available.9 Many of the other objections might be resolved by the vigorous international biobank harmonisation and data-pooling strategies underway by bodies such www.thelancet.com Vol 369 June 16, 2007
Design
Sample size
Cohort
500 000
40–69
Recruitment
Kadoorie Study of Chronic Disease Cohort in China (KSCDC)
500 000
35–74
Recruitment, follow-up
UK Biobank
Age at recruitment Status (years)
LifeGene (Sweden)
Cohort
500 000
Up to 55
Cancer Prevention Study-3 (CPS-3) (USA)
Cohort
500 000
30–65
Pilot
Preparation
Singapore Consortium of Cohort Studies
Cohort
250 000
21–65
Pilot
LifeLines (Netherlands)
Cohort
165 000
Various
NUgene (USA)
Cohort
100 000
≥18
Preparation
National Children’s Study (USA)
Birth cohort 100 000
From birth
Pilot
Estonian Genome Project
Cohort
100 000
≥18
Pilot
Joondalup Family Health Study (Australia)
Cohort
80 000
Various
Pilot
Preparation
Table: Biobank initiatives13
as the Public Population Project in Genomics (P3G) and HuGENet.10–12 These initiatives are important, because no currently proposed individual biobank will have sufficient statistical power to reliably answer all the important scientific questions that need to be addressed over the next decade.3,6 There are 87 population-based biobank projects extant or under development (table). The UK Biobank must continue to make every effort to harmonise and integrate with these other biobanks,11 and UK funding bodies must continue to support existing and new comprehensive lifespan cohorts. The UK Biobank is a big idea that, like all bold visions, will continue to attract plaudits and criticism. One of the key national benefits might simply prove to be the enablement of the physical and intellectual infrastructures that are being constructed by the project. This vision has taken much time and resources, together with energy and commitment on the part of the investigators and staff. As a result, the UK now stands at the threshold of an extraordinary cohort opportunity and a sentinel achievement—another step to the discovery and use of the genes and modifiable environmental factors underlying common diseases. Lyle J Palmer Laboratory for Genetic Epidemiology, Western Australian Institute for Medical Research and UWA Centre for Medical Research, University of Western Australia, Perth, WA 6008, Australia [email protected] I am involved in biobanking initiatives in Western Australia, and in P3G and HuGENet.
1981
Comment
1 2 3
4 5 6 7
UK biobank. Welcome to UK Biobank. http://www.ukbiobank.ac.uk (accessed June 7, 2007). Ollier W, Sprosen T, Peakman T. UK Biobank: from concept to reality. Pharmacogenomics 2005; 6: 639–46. Burton PR, Hansell A. UK Biobank: the expected distribution of incident and prevalent cases of chronic disease and the statistical power of nested case control studies. UK Biobank Technical Reports. Manchester: UK Biobank, 2005. Coghlan A. One million people, one medical gamble. New Sci 2006; 189: 8–9. Manolio TA, Bailey-Wilson JE, Collins FS. Genes, environment and the value of prospective cohort studies. Nat Rev Genet 2006; 7: 812–20. Hunter DJ. Gene-environment interactions in human diseases. Nat Rev Genet 2005; 6: 287–98. Davey Smith G, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 2003; 32: 1–22.
8
9
10 11 12
13
Timpson NJ, Lawlor DA, Harbord RM, et al. C-reactive protein and its role in metabolic syndrome: mendelian randomisation study. Lancet 2005; 366: 1954–59. Dwyer T, Hosmer D, Hosmer T, et al. The inverse relationship between number of steps per day and obesity in a population-based sample—the AusDiab study. Int J Obes (Lond) 2007; 31: 797–804. p3g Public Population Project in genomics. http://www.p3gconsortium.org (accessed June 7, 2007). Ioannidis JP, Gwinn M, Little J, et al. A road map for efficient and reliable human genome epidemiology. Nat Genet 2006; 38: 3–5. National Office of Public Health Genomics, CDC. Human Genome Epidemiology Network. http://www.cdc.gov/genomics/hugenet (accessed June 7, 2007). p3g Observatory. http://www.p3gobservatory.org (accessed June 7, 2007).
Synchrotrons as “super microscopes”
Diamond Light Source Ltd
The synchrotron, as a tool for physicists, has been around for well over half a century. Via magnetic and electric fields, subatomic particles can be accelerated to velocities within 0·1% or so of the speed of light (in cyclotrons neither can be varied but with synchrotrons both can). A feature of these beams that is unhelpful to physics is proving a boon for structural biologists and others.1 Accelerated electrons lose energy in the form of synchrotron radiation or “light”, especially high-intensity X-rays, which are being used in a variety of applications (table), and also as infrared and ultraviolet. The Diamond Light Source (DLS), Didcot, Oxfordshire, UK, opened for business in March this year.2,3
Diamond Light Source synchotron
1982
Not before time some would say: this £260 million project has had a long and chequered history.4 DLS is not the largest of the world’s 70 or so existing or planned synchrotrons, being a mere 170 m in diameter, or the most energetic at 3·5 GeV, but it is very versatile. Importantly, the beams are thousands of times brighter than those available from the synchrotron at Daresbury, Warrington, Cheshire, UK, and they are vastly more intense than conventionally sourced X-rays. After linear acceleration, particles pass to a circular booster and then on to the larger storage ring. Insertion magnets allow X-rays to be tailored to the requirements of individual projects and drawn off down beamlines to the experimenters’ workstations. So far, DLS has seven of these beamlines; 15 more are in the pipeline at a further £8 million each, and in time there might be 40. Although the synchrotron will run 24 h a day, competition for access is likely to remain fierce and the first list of users has been drawn from 127 applications received last year. X-ray crystallography has long been a mainstay of studies of biomolecular structure (eg, myoglobin and DNA from the 1950s) and DLS has been funded 86% by government and 14% by a medical research charity, the Wellcome Trust. France has recently inaugurated a similar multifunctional synchrotron light source (Soleil), and longer established ones include the US Center for Synchrotron Biosciences at Brookhaven, Upton, New York, USA.5 The huge European Organisation for Nuclear Research (CERN) facility, though predominantly a particle physics resource, has biomolecular applications. Therefore, there is www.thelancet.com Vol 369 June 16, 2007
tool. Scale-up of such implementation efforts would also include increased efforts to bundle community-directed treatment with ivermectin with preventive chemotherapy treatments for other high-prevalence neglected tropical diseases.9 However, when possible, monitoring and evaluation of both community-directed and integrated control programmes for neglected tropical disease should include best-practice efforts to detect the emergence of anthelmintic drug-resistance. Simultaneously, we need to anticipate the possibility of further ivermectin resistance and greatly increase our current level of effort and support to develop and test a new generation of control tools for onchocerciasis. Such tools would include better diagnostics, alternative microfilaricides such as moxidectin, and innovative anti-Wolbachia therapies.2,10 The development of a new-generation macrofilaricide for O volvulus continues to be an elusive goal, but remains a high priority. As an alternative but complementary approach, we now have several promising Onchocerca vaccine antigens and the proof of concept that protection against onchocerciasis can be experimentally induced.11–13 Many of the O volvulus antigens are orthologues of other helminth vaccine antigens currently under development.13 We therefore need to look at strategies by which a new generation of vaccines against O volvulus could be developed and linked with community-directed treatment with ivermectin in a programme of vaccine-linked chemotherapy.13 Now is the time for global health leaders to build on the strengths of community-directed treatment with ivermectin, and advocate and support
the development, testing, and distribution of a new generation of onchocerciasis-control tools. Peter J Hotez Sabin Vaccine Institute and Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC 20037, USA [email protected] I declare that I have no conflict of interest. 1
2 3
4
5 6
7
8 9
10 11
12 13
Levine R and the What Works Working Group. Case 6, controlling onchocerciasis in Sub-Saharan Africa. In: Millions saved, proven successes in global health. Washington DC: Center for Global Development, 2004: 57–64. Basanez MG, Pion SDS, Churcher TS, Breitling LP, Little MP, Boussinesq M. River blindness: a success story under threat. PLoS Med 2006; 3: e371. Amazigo UV, Brieger WR, Katabarwa M, et al. The challenges of community-directed treatment with ivermectin (CDTI) within the African Programme for Onchocerciasis Control (APOC). Ann Trop Med Parasitol 2002; 96 (suppl 1): S41–58. Seketeli A, Adeoye G, Eyamba A, et al. The achievements and challenges of the African Programme for Onchocerciasis Control (APOC). Ann Trop Med Parasitol 2002; 96 (suppl 1): S15–18. Boatin BA, Richards FO Jr. Control of onchocerciasis. Adv Parasitol 2006; 61: 349–94. Osei-Atweneboana MY, Eng JKL, Boakye DA, Gyapong JO, Prichard RK. Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in endemic communities in Ghana: a two phase epidemiological study. Lancet 2007; 369: 2021–29. Eng JK, Blackhall WJ, Osei-Atweneboana MY, et al. Ivermectin selection on β-tubulin: evidence in Onchocerca volvulus and Haemonchus contortus. Molec Biochem Parasitol 2006; 150: 229–35. Hotez PJ. The National Institutes of Health roadmap and the developing world. J Invest Med 2004; 52: 246–47. Molyneux DH, Hotez PJ, Fenwick A. “Rapid-impact interventions”: how a policy of integrated control for Africa’s neglected tropical diseases could benefit the poor. PLoS Med 2005; 2: e336. Taylor MJ, Bandi C, Hoerauf A. Wolbachia bacterial endosymbionts of filarial nematodes. Adv Parasitol 2005; 60: 245–84. Lustigman S, James ER, Tawe W, Abraham D. Towards a recombinant antigen vaccine against Onchocerca volvulus. Trends Parasitol 2002; 18: 135–41. Nutman TB. Future directions for vaccine-related onchocerciasis research. Trends Parasitol 2002; 18: 237–39. Hotez PJ, Ferris MT. The antipoverty vaccines. Vaccine 2006; 24: 5787–99.
UK Biobank: bank on it See Editorial page 1974
1980
The UK Biobank1 aims to include 500 000 people from the UK who are aged 40–69 years.2 The project will involve baseline questionnaires and physical measures (eg, standard anthropometry and spirometry), and will store blood and urine samples. The strategy is to collect baseline data on a large general population sample, to obtain broad consent from participants for unspecified health research, and to follow up the participants through linked population-level UK medical and other health-related records so that nested case-control studies of a wide range of common adult diseases can be investigated. The longterm goal is to explore the aetiology of common complex
diseases by investigation of their association with underlying genetic and lifestyle determinants. Samplesize calculations indicate that, with realistic assumptions, UK Biobank will be sufficiently powered to detect a main-effect odds ratio of 1·3 or higher after 6 years of incident-case collection for type 2 diabetes, after 8 years for diseases with an incidence profile similar to coronary heart disease, and close to 20 years for diseases with an incidence profile similar to stroke, Alzheimer’s disease, and breast or prostate cancer.3 An integrated pilot study took place for the UK Biobank between February and June, 2006. The aim www.thelancet.com Vol 369 June 16, 2007
Comment
was to test the recruitment process at the throughput required for the main phase. Around 3800 participants (about a tenth of those asked) attended the single pilot centre. Although the overall response rate is cause for some concern, the pilot was judged a success. The low response rate will probably follow through to the main study and means that the UK Biobank will clearly never be fully representative of the UK population. Such under-representation will not matter for many of the project’s aims. The main study is now fully funded (£59 million), began in February, 2007, and will finish in 2010. A large population-based cohort by itself does not guarantee success in aetiological studies of complex diseases, and the UK Biobank and other similar projects have been criticised.4 Objections include: that specific disease-focused case-control studies would be more efficient; only limited deep phenotyping (objective physiological measures) is being done; the age-range is not representative of the general population and many of the relevant exposures will have occurred previously; and that the projected time-lines to develop sample sizes of incident cases with sufficient power to detect realistic effect sizes are too long (at least 10 years for most diseases). The study is also predicated on the common-disease common-variant hypothesis. All these objections have some validity, although they also involve substantial subjectivity. An important lesson from the past decade of complex-disease genetic epidemiology is that there is no one model for gene discovery, study design, or analytic approach that will be the best in all situations. Both case-control and cohort designs are likely to be necessary,5,6 (especially in the context of gene–environment interaction6 and Mendelian randomisation approaches7,8). The UK Biobank now seems to represent an optimised solution for its funding and target sample size. However, the overall value of the study would be greatly enhanced with more detailed physiological phenotyping on all or some of the participants. There is growing evidence that the correlation between objective measures and questionnaire data for key indices (eg, physical activity) can be poor and lead to misleading conclusions if only the self-reported data are available.9 Many of the other objections might be resolved by the vigorous international biobank harmonisation and data-pooling strategies underway by bodies such www.thelancet.com Vol 369 June 16, 2007
Design
Sample size
Cohort
500 000
40–69
Recruitment
Kadoorie Study of Chronic Disease Cohort in China (KSCDC)
500 000
35–74
Recruitment, follow-up
UK Biobank
Age at recruitment Status (years)
LifeGene (Sweden)
Cohort
500 000
Up to 55
Cancer Prevention Study-3 (CPS-3) (USA)
Cohort
500 000
30–65
Pilot
Preparation
Singapore Consortium of Cohort Studies
Cohort
250 000
21–65
Pilot
LifeLines (Netherlands)
Cohort
165 000
Various
NUgene (USA)
Cohort
100 000
≥18
Preparation
National Children’s Study (USA)
Birth cohort 100 000
From birth
Pilot
Estonian Genome Project
Cohort
100 000
≥18
Pilot
Joondalup Family Health Study (Australia)
Cohort
80 000
Various
Pilot
Preparation
Table: Biobank initiatives13
as the Public Population Project in Genomics (P3G) and HuGENet.10–12 These initiatives are important, because no currently proposed individual biobank will have sufficient statistical power to reliably answer all the important scientific questions that need to be addressed over the next decade.3,6 There are 87 population-based biobank projects extant or under development (table). The UK Biobank must continue to make every effort to harmonise and integrate with these other biobanks,11 and UK funding bodies must continue to support existing and new comprehensive lifespan cohorts. The UK Biobank is a big idea that, like all bold visions, will continue to attract plaudits and criticism. One of the key national benefits might simply prove to be the enablement of the physical and intellectual infrastructures that are being constructed by the project. This vision has taken much time and resources, together with energy and commitment on the part of the investigators and staff. As a result, the UK now stands at the threshold of an extraordinary cohort opportunity and a sentinel achievement—another step to the discovery and use of the genes and modifiable environmental factors underlying common diseases. Lyle J Palmer Laboratory for Genetic Epidemiology, Western Australian Institute for Medical Research and UWA Centre for Medical Research, University of Western Australia, Perth, WA 6008, Australia [email protected] I am involved in biobanking initiatives in Western Australia, and in P3G and HuGENet.
1981
Comment
1 2 3
4 5 6 7
UK biobank. Welcome to UK Biobank. http://www.ukbiobank.ac.uk (accessed June 7, 2007). Ollier W, Sprosen T, Peakman T. UK Biobank: from concept to reality. Pharmacogenomics 2005; 6: 639–46. Burton PR, Hansell A. UK Biobank: the expected distribution of incident and prevalent cases of chronic disease and the statistical power of nested case control studies. UK Biobank Technical Reports. Manchester: UK Biobank, 2005. Coghlan A. One million people, one medical gamble. New Sci 2006; 189: 8–9. Manolio TA, Bailey-Wilson JE, Collins FS. Genes, environment and the value of prospective cohort studies. Nat Rev Genet 2006; 7: 812–20. Hunter DJ. Gene-environment interactions in human diseases. Nat Rev Genet 2005; 6: 287–98. Davey Smith G, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 2003; 32: 1–22.
8
9
10 11 12
13
Timpson NJ, Lawlor DA, Harbord RM, et al. C-reactive protein and its role in metabolic syndrome: mendelian randomisation study. Lancet 2005; 366: 1954–59. Dwyer T, Hosmer D, Hosmer T, et al. The inverse relationship between number of steps per day and obesity in a population-based sample—the AusDiab study. Int J Obes (Lond) 2007; 31: 797–804. p3g Public Population Project in genomics. http://www.p3gconsortium.org (accessed June 7, 2007). Ioannidis JP, Gwinn M, Little J, et al. A road map for efficient and reliable human genome epidemiology. Nat Genet 2006; 38: 3–5. National Office of Public Health Genomics, CDC. Human Genome Epidemiology Network. http://www.cdc.gov/genomics/hugenet (accessed June 7, 2007). p3g Observatory. http://www.p3gobservatory.org (accessed June 7, 2007).
Synchrotrons as “super microscopes”
Diamond Light Source Ltd
The synchrotron, as a tool for physicists, has been around for well over half a century. Via magnetic and electric fields, subatomic particles can be accelerated to velocities within 0·1% or so of the speed of light (in cyclotrons neither can be varied but with synchrotrons both can). A feature of these beams that is unhelpful to physics is proving a boon for structural biologists and others.1 Accelerated electrons lose energy in the form of synchrotron radiation or “light”, especially high-intensity X-rays, which are being used in a variety of applications (table), and also as infrared and ultraviolet. The Diamond Light Source (DLS), Didcot, Oxfordshire, UK, opened for business in March this year.2,3
Diamond Light Source synchotron
1982
Not before time some would say: this £260 million project has had a long and chequered history.4 DLS is not the largest of the world’s 70 or so existing or planned synchrotrons, being a mere 170 m in diameter, or the most energetic at 3·5 GeV, but it is very versatile. Importantly, the beams are thousands of times brighter than those available from the synchrotron at Daresbury, Warrington, Cheshire, UK, and they are vastly more intense than conventionally sourced X-rays. After linear acceleration, particles pass to a circular booster and then on to the larger storage ring. Insertion magnets allow X-rays to be tailored to the requirements of individual projects and drawn off down beamlines to the experimenters’ workstations. So far, DLS has seven of these beamlines; 15 more are in the pipeline at a further £8 million each, and in time there might be 40. Although the synchrotron will run 24 h a day, competition for access is likely to remain fierce and the first list of users has been drawn from 127 applications received last year. X-ray crystallography has long been a mainstay of studies of biomolecular structure (eg, myoglobin and DNA from the 1950s) and DLS has been funded 86% by government and 14% by a medical research charity, the Wellcome Trust. France has recently inaugurated a similar multifunctional synchrotron light source (Soleil), and longer established ones include the US Center for Synchrotron Biosciences at Brookhaven, Upton, New York, USA.5 The huge European Organisation for Nuclear Research (CERN) facility, though predominantly a particle physics resource, has biomolecular applications. Therefore, there is www.thelancet.com Vol 369 June 16, 2007