I-SIS Special Series, Inside Human Genetic and Genomics, Part 2
'Health genomics' promises to 'revolutionalise healthcare' in the new millennium. Britain is forging ahead with plans to set up a human DNA 'Biobank' collection Dr. Mae-Wan Ho and Nick Papadimitriou tell us why the Biobank assets are not worth the huge investments required, and call for wide-ranging open debate.
A decade and hundreds of millions invested in sequencing the human genome left the British government with the problem of how to justify the expense. As genes in themselves tell us little about the vast majority of diseases, the hope is that studying how genes interact with environment and lifestyle will bring returns on the huge outlay. That led to the idea of a human DNA collection.
The plan is to recruit a cohort of 500,000 volunteers in the age group 45-64 to provide DNA in blood samples. The samples are to be analysed and stored alongside personal data and medical records. This would enable geneticists to identify the genes associated with increased susceptibility to diseases, to find ways in which genetic variation can be used to 'personalise' treatment of diseases, and to elucidate the complex interactions between genes and environment in their effects on health.
The MRC carried out a consultation more than a year ago  with 350 members of the public, which included spokespersons from religious and ethnic groups and relatives of the seriously ill. Interviews were conducted with individual GPs and nurses, and representatives from organisations with a "special interest" in genetics research. "Controls" were imposed on the selection of the consulted in order to exclude those with a "strongly negative view" about medicine or genetics.
A workshop on protocol development was held in April 2001, and a report published on Wellcome Trust website in August . This is now subject to further reviews, to be finalised by the Protocol Development Committee and published in January 2002. Our contact says that this is when the public debate is supposed to begin. The project has changed its name, for at least the second time, from 'Biomedical Collection' to "BioBank UK."
Despite the selective nature of the consultation, a plethora of concerns were raised by those consulted. Special interest groups had mixed views on the Wellcome Trust and the MRC. Some believed that "both organisations were subject to pressure from pharmaceutical companies and the Government, and too willing to work to an agenda against the interests of people with disabilities" .
In the subsequent workshop on protocol development, further problems emerged particularly regarding the logistics of co-ordination, and the financial implications. The MRC has committed 20million to the project, and the Wellcome Trust is set to commit the same, although this amount of funding clearly falls far short of what is needed. But funding is not the only problem.
The cohort will consist of volunteers who would 'opt in', and the study will be prospective, ie, the volunteers must be healthy at the start. Unfortunately, the general public knows next to nothing about the proposal. Recruitment will be difficult, as there is no clear benefit to the participants. And even if a sufficient number of volunteers can be recruited, there might be insufficient numbers falling ill or dying to give statistically significant results.
More importantly, there will be variations due to geography, social class and ethnicity. Are those to be treated as "background ("nuisance") variables", or will the cohort be specifically designed to investigate these sources of variation? The suggestion was made that the study might investigate the interaction between genes and social class! The negative influence of social class on disease is well documented. But no one has seriously thought there might be class-specific genes.
Ethnicity too, is important, but for another reason. The effects of individual genes are often altered in dramatic ways, simply because the genes are in a very different genetic background (the combination of all other genes in the genome) in different ethnic groups. Geography was not even discussed, for the effects of environmental pollutants are strictly off the agenda, as it is also known that they are responsible for damaging every organ system in our body, including our genes.
The study is intended to focus on diet, exercise and other 'lifestyle' habits. Again, there is already overwhelming evidence that lifestyle factors can significantly prevent disease and slow disease progression across ethnic groups that differ in thousands, if not tens of thousands of genes.
What all this means is that any genetic susceptibility will be swamped by the social and environmental factors, ie, geography, social class, ethnicity, and lifestyle. It is hard to see how there can be significant findings from the BioBank project that could justify the huge investments called for. It is a hangover from the human genome project, and still driven by the same genetic determinist ideology that has been thoroughly discredited as the human genome map unfurled .
The collection and analysis of samples is already a daunting task, and it will take place in many regional centres, with central co-ordination. In addition, a massive longitudinal follow-up database is to be created. The problems of co-ordinating the efforts are immense, and include compatibility between different clinical systems, quality control, data storage, maintenance of anonymity, and linkage between different centres. Not the least of the problems is a lot of extra work for nurses and GPs, both already under intolerable pressures, and quite unable to cope from their normal workload .
The diseases studied are wide-ranging, and include cardiovascular disease, diabetes and metabolic disorders, respiratory diseases such as asthma and infections, mental disorders such as Alzheimer's and Parkinson's, cancers, and musculoskeletal disorders such as osteoporosis, arthritis and spinal disc degeneration.
There was a strong feeling that proper informed consent must be obtained, and that it must be made clear to the participants as to what they are consenting to. But what if the collection is to be used for a different purpose in future, to study other diseases, or intelligence as was suggested or other behaviour? Would participants be required to give carte blanche consent?
Given that the aim of the project is to correlate individual DNA samples with lifestyle and health records, the data must be coded to maintain anonymity. How could anonymity be maintained, and who should safeguard this anonymity? There was a suggestion that oversight by an independent body would "reassure the public that the data were being managed and used in the public interest". Will industry have access to the database? And will the police have access to it for forensic or purely civil surveillance purposes, or as governments might demand, as 'emergency anti-terrorist measure'?
If, in the course of analysing the DNA samples, a gene associated with a serious disease is found, should anonymity be broken so that the participants could be informed, in particular, if the disease could be prevented by treatment? And should treatment be given? It would be unethical not to, but that would mean the samples will be lost to the study.
And if the participants were to be informed of their genetic status, they would have to tell their insurance company, and they may be refused insurance they might otherwise obtain, or be denied employment. The British public is overwhelmingly opposed to insurance companies using genetic information to decide whom to insure or to set premiums (Box 1).
The answer is almost certainly yes, otherwise there will be no point to the project. Top level discussions were held by a panel selected by Health Secretary Alan Milburn, to draw up a green paper around the possibility that DNA samples held by the NHS might be passed on to biotech companies . The government's Economic and Social Research Council is to set up a research centre to explore the social and economic implications of genomics (Box 1). And £30m has been invested in the NHS to make it a "world leader in genetics" .
The Human Genetics Commission insisted back in 2000 that findings from this research would not readily be made available to pharmaceutical companies . What that means is that no individual medical record will be given to the company, and anonymity will be maintained, but commercial exploitation will go ahead all the same. Pharmaceutical companies are already reportedly eagerly awaiting the discovery of 'druggable targets' and personalized medicine . Pharmaceutical companies will be able to 'mine' this public database the same way they have mined the human and other genome sequences in the public domain, and will be patenting gene sequences and genetic medicines arising from the database. One of the potential uses of the database may be to encourage people to change their diet or lifestyle to improve their health. Companies, however, have a vested interest not to promote a change in habit or lifestyle so they can sell drugs.
There is currently an agreement between the Government and the insurance industry on a five-year freeze on using genetic tests, except for high-value policies. Tests for genetic susceptibility to diseases such as cancer can continue to be added to an approved list and used to determine access to high-value policies throughout the five year freeze.
Four out of five people in Britain believe that genetic information should not be used in setting insurance premiums (Box 2). The members of the public consulted by MRC expressed similar concerns.
But one of the most important objections is the unreliability of such information. Susceptibility genes, even if they exist, are by definition, uncertain. In particular, they are attributes of a population, and not of any single individual . The quest for 'personalised' medicine based on individual genetic makeup is simply scientific nonsense.
The Icelandic DNA population collection - the first and only in existence to-date - was set up historically with minimum public consultation. As a consequence there was no opportunity for public debate on any of the issues outlined above. We are told that the findings of the consultation on the UK BioBank are "statistically insignificant." This may justify ignoring the concerns expressed by the members of the public who were actually consulted.
It is astonishing that this large research project, fundamentally flawed, and with such disturbing implications should have reached the protocol stage without any real public debate. This must now take place without delay.
Box 1 Government-funded research centre to explore the social and economic implications of genomics
The UK Government's Economic and Social Research Council (ESRC) plans to set up a research centre to explore the social and economic implications of genomics. As a first step, ESRC commissioned the Centre for Research on Innovation and Competition (CRIC) at Manchester University and the US based Institute for Alternative Futures (IAF) to outline the direction the research should take. CRIC was set up by ESRC in 1997 and, to quote its own web-site, "its ambitious aim is to contribute to the fundamental understanding of the complex issues that underline and link together innovation and competitiveness." CRIC studies the contribution of innovations to the competitiveness of British companies and services.
IAF is staffed by self-styled "futurists," and includes Alvin Toffler, prophet of "third wave" economics among its founders. IAF promotes 'adaptive decentralised' approaches to economics, is committed to helping clients fulfil their "preferred futures" and champions free market enterprise. While ostensibly post-industrial both in its advocacy of individualistic self-fulfilment and in its sensitivity to cultural microclimates, IAF is likely to promote genomics precisely because one of the professed aims of genomics, the tailoring of drugs to suit specific genes, is the sort of adaptable niche targeting IAF favours. Several documents produced by IAF take the view that market forces provide the fertile ground necessary for the exploitation of genomics. One of these, "21st Century Health Care in Latin America and the Carribean," sponsored by Smith Kline Beecham, makes the following remarks about genomics:
Box 2 British public opposed to use of genetic information by insurance companies
A survey of social attitudes compiled and published by the National Centre for Social Research showed 8 out of 10 people opposed to insurance companies using genetic test results. The Government's decision to impose a five-year moratorium is in tune with public opinion.
The government and the Association of British Insurers recently agreed that, from the start of this November, consumers would be able to buy all but the most expensive insurance policies without having to disclose genetic test results. So far, the only genetic test approved for insurance purposes is for the hereditary degenerative disease Huntington's chorea.
The British Social Attitudes survey findings confirm those of the Human Genetics Commission, a government advisory body. However, 75 per cent of people believe that within the next 25 years, insurers will be using genetic data to calculate premium levels.
The Consumers' Association is calling for an outright ban on insurance companies using genetic test results and is concerned that widespread use of genetic information could lead to an uninsurable "genetic underclass".
Source: "Public opposition to genetic testing" by Vivienne Russell, 28 November, 2001, London, Health Media Ltd 2001
Article first published 05/10/09
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