News

27 January 2006Two articles in the British Medical Journal support the Academy of Medical Sciences (AMS) report calling for reform of personal medical data regulations. The AMS report specifically highlighted a strict interpretation of the requirements of the Data Protection Act 1998 by regulators as one of the major factors impeding research using personal medical data. These articles continue the debate.

 

Amy Iversen and her co-authors (including Kathleen Liddell, Law Lecturer at the University of Cambridge and the CGKP) report on their difficulties in conducting epidemiological research involving UK military personnel [Iversen, A et al. 2006 BMJ 332:165-169]. In previous years the team says that they had been able to obtain personal data about personnel from the Ministry of Defence, without consent, to examine the health effects of serving in the 1991 Gulf and 2003 Iraq wars. The Ministry cooperated with the researchers “…taking into account the public health importance of the study and legal advice on the obligation of the previous Data Protection Act.” However, when the team attempted to continue their studies in 2004, the team were then required to obtain consent from individuals. As epidemiological studies require large numbers of participants (one of their earlier studies numbered over 8000 participants), contacting each person will most likely be impractical. Iverson and colleagues argue that requiring consent will reduce the sample for the study (as its difficult to contact large number of people) and will bias the study, as those people with a vested interest in the research are more likely to agree to participate. The authors state that the law allows personal data to be released without consent of the individual, subject to safeguards. Continuing to interpret the Data Protection Act in a restrictive manner will inhibit and negatively impact epidemiological research.

 

In the second article in the BMJ, Tom Walley, Chair of the Research Governance Group at Royal Liverpool and Broadgreen University Hospitals, Liverpool, states that, “…recent regulation of research involving patients or their personal data…has caused delays, higher costs, and sometimes cessation of research projects” [Walley, T. 2005 Science 332:130-131]. He argues that the potential harm to an individual from epidemiological research is minimal, as opposed to interventional research (such as a clinical trial). However, “…people have misinterpreted the regulations to imply that both types of research have similar standards for informing patients and obtaining consent.” The fact that these kinds of studies have different risk/benefit ratios should be taken into account when committees consider whether informed consent is necessary for a study. In addition, he agrees with the AMS that more research is needed to determine the public’s attitude towards use of their personal data in epidemiological research.

 

There are those who argue that the Data Protection Act is not being interpreting in an overly restrictive way. Richard Thomas, the Information Commissioner, argues in a letter to the Times newspaper that the central issue is confidentiality of patient information, not an overzealous interpretation of the Act. But, according to the AMS report and claims from researchers, continued debate is needed on this issue if epidemiological research, that can benefit the public and their health, is not to suffer.

31 January 2006The Human Genetics Commission (HGC) has released their report, Making Babies: Reproductive decisions and genetic technologies. Their aim is “…to provide a useful framework for future debate and policy in the United Kingdom” on the subject of how developments in human genetics have influenced the public and society in the area of reproductive decision-making. The HGC consulted with stakeholders and the public and have analysed the approximately 200 responses they received. In addition, they considered the conclusions reached by a Citizen’s Jury of 16-19 years old that examined the issue of ‘designer babies,’ as well as comments received from the HGC’s Consultative Panel.

 

The HGC reached four general conclusions based on their deliberations. Firstly, individual choices must be balanced against the potential for harm to other individuals or society, thus justifying some restrictions on unfettered choice. Secondly, for some ‘trivial’ or non-medical conditions it would be inappropriate to engage genetic technologies. Thirdly, the choices made by persons and the consequences of those choices should be supported and respected by society; for example, not engaging in prenatal screening. Fourthly, there should be ‘systematic follow up’ of children born as a result of new technologies, such as preimplantation genetic diagnosis (PGD), in order to determine any long-term consequences.

 

More specifically, the HGC makes recommendations in the areas of prenatal and neonatal screening and diagnostic testing; PGD; assisted reproductive technologies, genetics and reproductive choice and the framework and organisation of genetic services. For example, they support continued research into better treatments for genetic conditions as well as appropriate services for those with genetic conditions. As noted, they call for the follow up of children who have been born using PGD or as the result of a tissue match for an ill sibling (‘saviour siblings.’) The HGC recognises that more research is needed to chart the effects of these technologies on the resulting children, as little safety evidence is available related to PGD or into the wellbeing of children born after tissue matching. Also the HGC endorses the work of the National Gamete Donation Trust in the provision of information related to gamete donation and supports the possible regulation of commercial operations involving sperm donation. Finally, the HGC makes clear that “The anxiety that PGD lies at the top of a slippery slope leading to the possibility of a wide range of potential enhancements, such as intelligence or beauty, is misplaced.” Such characteristics involve a complex interaction of many genes, as well as other developmental factors, and finding an embryo with the desired combination is “…very unlikely.”

19 January 2006The Academy of Medical Sciences (AMS) has called on regulators to reform guidance on the use of personal medical data in research. Their newly published report, ‘Personal data for public good: using health information in medical research,’ outlines their concerns and makes recommendations for what they see as possible improvements to research practices.  

 

Reform is needed, according to the AMS, because data protection and other related legislation has often been interpreted by regulatory bodies in contradictory and confusing ways. Because of the resulting uncertainty, researchers are often advised that personal medical data cannot be used in their research studies unless there is consent from the individual or the data has been anonymised. For many research projects this might be impracticable and studies are either not done or delayed significantly while researchers try to meet these strict requirements. As a result, these contradictory interpretations are hindering research aimed at public health. According to the report, “Identifiable data can be used for medical research without consent, provided that such use is necessary and is proportionate with respect to privacy and public interest benefits.” This message needs to be made clear to researchers and the different bodies that approve research “…should accept this interpretation in their guidance and approval decisions.”

 

The report makes several other recommendations. It calls for improvements in and a simplification of the regulatory process for approving research proposals. In addition, the Department of Health should make certain that research needs are fully integrated into the forthcoming NHS Programme for IT, through the Connecting for Health electronic ‘care record.’ Additional research is also needed into determining how the public feels about research using their personal data. Anecdotal evidence appears to show that the public is supportive of this research and have confidence in the integrity of research practices. However, little empirical evidence is available to support this; the Academy has called on the Department of Health and the UK Clinical Research Collaboration to fund studies and public engagement activities around this issue. 

 

Equally important, notes the report, is the need to ensure that researchers follow good practice in using personal medical data, to show they deserve the public’s support. They must be made aware of relevant legislation, research governance policy and processes and their underlying ethical principles. The report recommends that good practice guidelines are developed to include data security, anonymisation, consent and the use of health records to identify potential research participants.

 

Research studies have been delayed or blocked by the regulators (see BBC news report 18/01/06) and the AMS sees the strict interpretation of the Data Protection Act 1998 as the major culprit. According to Prof Robert Souhami, chair of the working group, “Since the 1990s regulators have been taking a stricter line and this is making it hard for researchers to get permission to carry out studies using personal data. The UK used to be a world leader on this, but it is not any longer.” The AMS hopes this report will raise awareness of these issues and prompt moves towards reform.

11 January 2006Seoul National University has concluded that Professor Woo-Suk Hwang did not produce the first cloned human embryo in 2004.

 

The University began an investigation into Professor Hwang’s work following allegations about the methods used to obtain human oocytes used in experiments (see previous newsletter item), but went on to look at the actual experimental results themselves. As reported previously, this preliminary investigation concluded that the Hwang lab had not produced the first patient-matched embryonic stem (ES) cell lines. The University’s final report has also concluded that the paper reporting the cloning of a human blastocyst by somatic cell nuclear transfer, and the derivation of an embryonic stem cell line from it, had also been fabricated.

 

The University Investigation Committee undertook DNA fingerprinting analyses on samples from the ES cell line (NT-1), as well as from the donor of the egg cell and somatic tissue. They found that the cell line did not have the same profile as that of the donor material, demonstrating that it could not have been derived following nuclear transfer from the donor. Comparison of 48 polymorphic loci in the NT-1 cell line and the egg donor showed that they were not identical but displayed 8 inconsistencies, proving that NT-1 was not an ES cell line derived from a cloned blastocyst. The Committee concludes that this data suggests, “that there is a high possibility that NT-1 resulted from the fusion of a non-enucleated egg and a nearby polar body, which initiated a parthenogenetic process” and that, “the claim in 2004 (Science) article that the DNA fingerprinting pattern of NT-1 and that of the donor A match perfectly was a clear false report”.

 

However, the Committee did find that the cloned dog, Snuppy, was a genuine clone of another dog from which somatic material had been taken. This finding was verified by DNA fingerprinting analysis.

 

The unravelling of the work of the South Korean lab, and Professor Hwang himself, who was once thought to lead the field in stem cell research, has caused much disappointment in the scientific community. However, numerous stem cell scientists and funding agencies have expressed the hope that these revelations, despite being major setback, do not significantly damage the reputation of legitimate science (see BBC news story). Professor Hwang himself has been quoted as saying that his work has been “sabotaged”, but he now faces the loss of his grants and national honours from the South Korean government.

10 January 2006The Estonian Genome Project (EGP) is a venture that aims to collect DNA samples, clinical data and other health-related information from the vast majority of the 1.4 million inhabitants of the East European country Estonia. A database on this scale would be immensely valuable for research into genetic and environmental factors that influence health and disease, including common complex diseases such as diabetes, depression and cardiovascular disease.

Founded in 2001, to date only around 10,000 donors have joined the project and its future has been uncertain since the original venture-capital funding came to an end. Now the Estonian government has announced plans to provide funds of €8 million (around £5.5 million) for the project, which should enable it to continue recruitment to 100,000 donors (see News in Brief, Nature 438, 902).

5 January 2006The Home Office has announced the release of its report on the achievements of the DNA Expansion Programme. The Programme was launched in April 2000 using Government funding to increase the number of profiles in the National DNA Database (NDNAD). The original target was to have a profile on file for all active offenders by March 2004. That target was reached; the Home Office now reports that the NDNAD has over 3 million profiles on record. This is the largest DNA database of any country, according to the report, with the largest proportion of any country’s population held on a database. 5.2% of the UK’s population is on the database, compared to the US with 0.5% and the average of the EU countries at 1.3%.

 

The report states that better crime detection has resulted from the expansion of the NDNAD. Detections of crimes using DNA have quadrupled. The expansion has enabled the police to have a greater number of profiles from which to find matches. This has been aided by legislation that came into force in April 2004 that allows police to take a DNA sample from any person arrested for, charged with, informed they will be reported for or convicted of a recordable offence. In addition to increasing the number of detections, the Home Office reports that the expanded database allows police to eliminate innocent parties or people that have legitimate access to a crime scene. Retaining samples helps solve crimes committed in the past (cold cases). The database may link offenders with a past crime when they are picked up for a minor offence at a later date. The Home Office also states that DNA is helping significantly with crimes that are difficult to detect, such as domestic burglary.

 

While the expansion helps to “…increase the intelligence value of the Database” according to the report, others have complained that the retention of samples is a breach of civil liberties. The BBC quotes Lynne Featherstone, the Liberal Democrat home affairs spokeswoman, as calling the retention, “…an intolerable infringement of liberty and personal privacy” (BBC news 04/01/06).   The National Black Police Association has called for the Government to investigate why there is an over-representation of black people in the NDNAD (BBC news 06/01/06). With DNA samples being retained even if the person is not charged, this could indicate that more black people are being taken into custody than from other groups. David Weaver, a spokesman for the 1990 Trust, a black-led human rights group, stated that the over-representation on the NDNAD made black people suspicious that they were being targeted.

 

With DNA Expansion Programme completed, the successor programme is the Forensic Integration Strategy (FIS). Under the FIS, the Home Office plans “…to optimise their use of forensic science, extending the UK’s global lead on the use of DNA to all forms of forensic intelligence.” For example, there are plans to improve the exchange of DNA intelligence on an international level.

4 January 2006The US National Institutes of Health (NIH) has launched the pilot phase of an ambitious human cancer genome project. The Cancer Genome Atlas (TCGA) will begin with a feasibility study on the intention to systematically catalogue the genetic changes associated with all forms of human cancers. Genomic changes are known to underlie cancer by disrupting normal mechanisms of controlled cellular growth and development; it is hoped that by cataloguing these changes it will be possible to develop novel therapeutic and diagnostic tools for cancer. The initial phase of the project will concentrate on a few selected types of cancer in order to develop and evaluate systems to identify and characterise mutations and other genetic alterations. It will also seek to develop new technologies, for example for the analysis of epigenetic changes such as methylation.

A Human Cancer Biospecimen Core Resource will process and distribute of cancerous and control tissue samples to centres for genome characterization and sequencing, looking for mutations and larger-scale genomic changes such as copy number changes and/or chromosomal translocations, that are known to contribute to cancer development. These centres will be chosen in 2006. TCGA data will be made publicly available to the international research community.

NIH Director Elias Zerhouni said: "This atlas of genomic changes will provide new insights into the biological basis of cancer, which in turn will lead to new tests to detect cancer in its early, most treatable stages; new therapies to target cancer at its most vulnerable points; and, ultimately, new strategies to prevent cancer" (see press release). NHGRI Director Francis S. Collins commented: "Given the genetic complexity of cancer, we are certain to face many daunting challenges in this pilot. But by pulling together some of the best minds in the cancer and genomics research communities, I am confident that the pilot will succeed, and we will go on to develop an atlas that will accelerate cancer research in ways we cannot even imagine today".

Funding for the project ($100 million over three years) will be provided by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). Project supporters have cited the success of the UK Cancer Genome Project run by the Wellcome Trust Sanger Institute as an exemplar of the potential benefits of such initiatives, but others think that the project may cost too much for limited benefits, and say that the money would be better spent on basic cancer research (see Check E (2005) Nature 438, 894).

3 January 2006Following the resignation of the internationally renowned South Korean stem cell researcher Professor Hwang Woo-Suk after controversy over ethical issues surrounding his latest work on the production of patient specific stem cell lines, a panel from Seoul National University (SNU) has announced its conclusion that these stem cells were never actually produced. The investigators reported that they were unable to find stem cells matching the DNA of patient tissues; researcher Roe Jung-hye said: "It is the panel's judgement that Professor Hwang's team does not have the scientific data to prove that they (patient-specific stem cells) were made" (see BBC news report). Hwang has submitted his resignation to Seoul National University, having already stepped down from public appointments, including the chairmanship of the World Stem Cell Hub, when the allegations of ethical irregularities were confirmed.

This news is a significant blow for stem-cell research; the groundbreaking paper published in Science in May 2005 reporting the production of eleven different patient-specific stem cell lines was hailed as a breakthrough in therapeutic cloning. Hwang has requested that the journal retract this paper but reportedly said that despite "various serious errors and shortfalls" his team had indeed created patient-specific stem cells and that his research techniques would be vindicated (see Science news report). Earlier published work by Hwang Woo-Suk is currently under review.

UK expert Alison Murdoch from the University of Newcastle-upon-Tyne, who leads a group licensed by the HFEA to conduct therapeutic cloning research, aid: “Hwang’s results shifted the research focus to emulating his work. Now we may need to look again at that fundamental step” [Check E (2005) Nature 438, 1058-1059]. Progress in this area has undoubtedly been slowed by the apparent falsification of data for publication by Hwang’s team, and public confidence in the field may also have been shaken; in future, it seems likely that more stringent peer-review processes will be put in place to assess papers submitted for publication.

10 January 2006A road map for efficient and reliable human genome epidemiology. Ioannidis JPA et al. (2006) Nature Genetics 38, 3-5. Commentary on the ‘Network of Investigator Networks’ initiative established by the Human Genome Epidemiology Network (HuGENet) proposals to develop means of efficient and robust means of compiling evidence for genetic contributions to disease risk. See also the editorial article Embracing Risk (Nature Genetics 38, 1), which outlines the journal’s new system for submission of genetic association studies, including those with negative findings. Widening the spectrum of human genetic variation. Eicheler EE (2006) Nature Genetics 38, 9-11. News and Views piece accompanying three research papers that report on deletions present within the human population, and illustrating how this expands the knowledge of human genetic variation by adding to the information on single-nucleotide polymorphisms (SNPs) in populations. Confronting ethnicity-specific disease risk. Tang H (2006) Nature Genetics 38, 13-15. News and Views article on a report from a multi-ethnic case control association study that identifies a genetic variant associated with increased risk of heart attack, but to a different degree in African American and European American groups. The epigenetic progenitor origin of human cancer. Feinberg AP, Ohlsson R and  Henikoff S (2006) Nature Reviews Genetics 7, 21-33. Review of evidence suggesting that despite the divergent genetic profiles of different cancers, there may be a common underlying basis based on polyclonal epigenetic disruption of stem / progenitor cells; the potential for prognosis and therapeutic intervention is also considered.

The role of double-strand break repair — insights from human genetics. O'Driscoll M and Jeggo PA (2006) Nature Reviews Genetics 7, 45-54. Review of the molecula processes in repair of DNA double-strand breaks and the role of human disorders in which double-strand break repair is compromised in understanding these processes.

 

Microarray data analysis: from disarray to consolidation and consensus. Allison DB, Cui X, Page GP and Sabripour M (2006) Nature Reviews Genetics 7, 55-65. A guide to the types of statistical analysis currently used for different stages of microarray experiments.

Science and society: Genetic profiling of newborns: ethical and social issues. Almond B (2006) Nature Reviews Genetics 7, 67-71. Perspectives article.

Science and society: Human dignity: a guide to policy making in the biotechnology era? Caulfield T and Brownsword R (2006) Nature Reviews Genetics 7, 72-76. Perspectives article on how the concept of human dignity is used in debate surrounding controversial biotechnology such as biobanks, human gene patents, stem cell research and human cloning, and how this usage differs from the traditional, human-rights informed view of human dignity.

3 January 2006Unnapproved tests on a chip. Nature (2005) 438, 711. Editorial deploring the absence of a regulatory framework for prenatal genetic tests, including DNA microarrays to scan for hundreds of genetic abnormalities, in the US. See also Screen test. Check E (2005) Nature 438, 733-734.

The dog has its day. Ellegren H (2005) Nature 438, 745-746. News and views feature on the sequencing of the dog genome and how it may contribute to understanding of human disease mechanisms.

Running the red light. Ainsworth C (2005) Nature 438, 726-728. News and views feature on nonsense-mediated decay (NMD) and how drugs may be used to block this process in some individuals with inherited disease.