Select Committee on Science and Technology Fourth Report

CHAPTER 4: Current and future benefits

4.1 Advances in both technology and the underlying science have led to an explosion of information on genetics in recent years.

4.2 As noted in previous Chapters, the human genome sequence provides no more than basic data. Practical health benefits will flow from coupling knowledge of the sequence with other advances in understanding not only gene and protein function but also the links between genetic information, lifestyle factors and disease occurrence.

Current benefits

4.3 Some of these benefits are already available, as outlined in Box 5. Others will take longer to realise. Professor Sir John Pattison, Director of Research and Development at the Department of Health, reminded us of the difficulties and uncertainties in making accurate predictions (Q 9). Professor John Bell, Nuffield Professor of Clinical Medicine at the University of Oxford (and representing the Academy of Medical Sciences), felt that fully understanding the complexities that underlie molecular and genetic interactions might take 100 years (Q 339).

Box 5

Some current benefits

·  A few drugs, such as fluoxetine (Prozac), are marketed with a genetic test available to supplement the assessment of the patient's suitability for receiving the drug before prescription (Sir John Pattison, Q 6).

·  The BRCA-2 gene is being used as a predictive diagnostic for breast cancer (Dr Dexter, Q 66).

·  Advances in gene-profiling of leukaemic cells have enabled the correct type of leukaemia to be diagnosed so that appropriate treatments can be instigated (Dr Dexter, Q 66).

·  The new discoveries are helping to develop the understanding of gene function. For example, the single gene cause of one form of muscular dystrophy affects the actions of 96 other genes (Sir George Radda, Q 65).

·  1100 disease-related genes (mainly for single-gene disorders) are documented on specialised databases, leading to new screening tests and improvements in diagnosis and disease prediction[23].

·  The sequencing of the genomes of infectious organisms (such as the tuberculosis bacillus) is helping to understand the mechanisms of infection and to develop new vaccines and treatments (Sanger Centre, Appendix 5).

·  In forensic applications, the National DNA Database has resulted in 100,000 matches between individuals and scenes of crime, including those responsible for 212 murders, 671 rapes and 479 serious robberies (Dr Werrett, Q 187).

4.4 A further boost to activity will result from the availability of a complete and annotated version of the human genome. According to the International Human Genome Sequencing Consortium, this should be available by 2003, if not sooner[24].

Future medical benefits


4.5 As noted in paragraph 3.6, many diseases (including common disorders such as Alzheimer's disease, asthma, diabetes and heart disease) appear to result from a complex interplay between genetic, environmental, dietary and lifestyle factors. As Roche (p 79) Sir George Radda (Q 67) and others noted, understanding these complex interactions will aid disease prevention. In its written evidence, the MRC stressed that the best preventive measures for these common disorders might prove to be dietary or lifestyle change (rather than drug therapy or regular health check-ups), against a genetic background that might predispose the individual to such diseases (p 63).

4.6 As noted in written evidence from Glaxo Wellcome, long-term epidemiological studies of large numbers of people are required to unravel the links between genetic background, environmental (or lifestyle) factors and the occurrence of disease. Such studies would offer new insights into the understanding of genetic predisposition to common diseases, and the role of gene-environment interactions in disease causation (p 49).

4.7 As we were told by Sir John Pattison, there is the potential to prevent or cure a genetic cause of disease at source through gene therapy, that is by replacing or modifying the abnormal disease-causing gene or by correcting its effects (Q 5).


4.8 As noted by the Academy of Medical Sciences, advances in genetic technology will bring improvements in the diagnosis and management of patients with genetic disorders (p 1), and allow the identification of groups of individuals who may be more susceptible to certain diseases (Q 354).

4.9 Sir John Pattison was clear that these advances would transform the assessment of the risk of developing certain diseases and communication this information to patients and their families (together with possible preventive action). These diseases include not only the single gene disorders, such as haemophilia and Huntington's disease, where having the affected gene carries a risk of developing the condition approaching 100 per cent, but also other conditions with a strong family history, such as the familial form of breast cancer (Q 5).

4.10 Professor Bell was excited about developments in the related and comparatively new field of proteomics - the ability to recognise and quantify in biological samples the whole range of proteins present. He felt that, within a few years, it would be possible to identify disease states perhaps many years before the disease became clinically apparent. This would have wide application in screening for the early detection and treatment of cancers, metabolic disease, coronary heart disease and a range of other conditions (QQ 346 & 347).


4.11 As noted by Roche (p 77) and others, pharmaceutical companies had four main interests in this field:

(a)  finding new targets for drugs to act on the disease mechanism;

(b)  identifying susceptibility genes (to common diseases) for early detection and prevention of disease;

(c)  identifying, from their genetic make-up, people who were likely to react adversely to a particular drug; and

(d)  identifying people who would benefit from particular drug treatments.

4.12 The last two areas are important in the field of pharmacogenetics - the tailoring of drug treatment to the genetic make-up of the patient[25] - with the aim of both maximising drug efficacy and minimising side-effects. Such tailoring of drugs to individuals would allow more effective drugs to be developed and marketed. Indeed, as noted by Dr T Michael Dexter, Director of The Wellcome Trust, the ability to identify those with the genetic make-up that might lead to adverse side effects might allow entry or re-entry to the market of drugs which would not be available under current regulations but which could be beneficial for some people (Q 66).

4.13 The pharmaceutical companies already collected genetic information in relatively small-scale studies from patients with specific diseases. As noted by AstraZeneca, the number of individuals from whom DNA samples were collected was set to increase substantially, especially from participation in clinical trials, providing an important source of information on genetically determined responses to treatment. Such samples would be collected from patients world-wide, so that the proportion of samples derived from patients in the United Kingdom would be relatively small (p 11).

4.14 AstraZeneca expected information on Single Nucleotide Polymorphisms (SNPs) to be used to localise disease genes and identify genes which would be useful drug targets (p 11). In a Lancet paper[26], Dr Allen Roses of GlaxoSmithKline suggested that, when drugs were released into the market in the future, blood spots stored on filter paper could be collected from a large number of patients, linked to prescription information. When severe adverse drug reactions were recorded, the SNP profile of patients experiencing the adverse events could be compared with a control group without such events, to identify SNP patterns associated with poor response. Similarly, a database could be constructed of SNP patterns associated with high efficacy and minimal side-effects.

4.15 Screening for the key SNP patterns (indicating high efficacy and absence of adverse effects) for instigation of drug therapy in a particular patient could be done rapidly and cheaply[27]. Dr Roses argued that such a system would offer considerable advantages over the current regulatory system. The present requirement was for extensive clinical trial data, but even very large trials were not big enough to detect rare adverse events. Because time and costs of bringing a drug to market would be reduced, it would be possible to tackle the rare diseases which are currently not commercially viable for the pharmaceutical companies to address (Q 201). There were also likely to be considerable health care savings as drug treatments could be targeted only at those who would respond[28].

The proposed UK population biomedical collection

4.16 The written evidence from the MRC and The Wellcome Trust (pp 63 & 99) described their joint proposal for a large-scale national study (the UK Population Biomedical Collection), being developed with the involvement of the Department of Health (p 32). This very substantial initiative was explored further in questioning Sir George Radda, Dr Dexter and Sir John Pattison (QQ 39 & 71-85).

4.17 The principal aim of the study would be to understand, in a genetically heterogeneous population such as the United Kingdom's, the contribution of gene/environment interaction in the development of disease, especially the common diseases. This would give greatly enhanced understanding of the causes and nature of disease and its progression, and would also inform strategies for disease prevention and treatment.

4.18 The proposed sample population would be 500,000 men and women volunteers, aged 45-64, from the United Kingdom. Various basic measurements (such as height, weight, blood pressure, lung function) would be recorded, together with details of medical history and lifestyle from questionnaires. Follow-up data on the participants' health and lifestyle would be collected over the succeeding years. Genetic analyses would be carried out on the volunteers (or subsets of them) by separate research groups, although the results would be held centrally to increase the value of the resource over time. Industry would be invited to join the research later on for specific projects that they would fund.

4.19 The pharmaceutical industry itself was generally supportive of the initiative as a whole and interested in collaborating in the research (PP 42, 57 & 58). Professor Bell stressed the importance of this research from the wider scientific perspective (QQ 349 & 350).

Forensic applications


4.20 In contrast to the medical applications which are the main focus of this Report, there are specific applications of genetic technology in the field of forensic science. As representatives of the Forensic Science Service (FSS) told us, this is used to create genetic profiles of individuals as an aid to solving crime (Q 107). Again in contrast to the medical applications, the forensic work had little interest in genes as such (Q 147).

4.21 The FSS's interests in genetic function extended only to their investigation of whether genetic technologies would assist the determination of distinctive traits (such as hair colour, eye colour, ethnicity, weight and height) which might ultimately contribute to the identification of individuals. Some considerable effort had gone into this type of work, but practical applications seemed still some way off (QQ 129-131).


4.22 As noted in the written evidence from the FSS (p 39), the National DNA Database was established in April 1995 for solving crime and the elimination of suspects. This was in response to recommendations made by the Royal Commission on Criminal Justice in 1993. It required changes in legislation as well as improvements in the sensitivity and discriminating power of the DNA profiling technique. The Criminal Justice and Public Order Act 1994 included powers to take non-intimate samples[29] from all those individuals charged, reported, cautioned or convicted for recordable offences since 10 April 1995 or who were convicted of sex, violence or burglary offences before that date if they were still serving a prison sentence at the time the sample was taken. Proposals in the Criminal Justice and Police Bill undergoing Parliamentary consideration during our Inquiry would allow suspects' DNA data (together with the associated samples) to be retained even if individuals were acquitted of the crimes for which the samples were taken (Q 133).

4.23 During oral evidence from the FSS and the Home Office, we heard that genetic profiles of samples[30] from individuals who had been arrested were put on the database, as were profiles of samples from scenes of crime (Q 107). The computer then searched for a match between the two data sets. DNA profiles from roughly 900,000 individuals and 100,000 scenes of crime were already on the database, with the numbers growing at between 25,000 and 30,000 a month (QQ 107, 110 & 111). So far around 100,000 matches had been reported from the database (Q 126).

4.24 The FSS, which held the database, was looking at new ways of automating the analytical process, including the possible use of SNPs (within 5 years) as an alternative to using short tandem repeats (Q 123). Currently, 10 sites or loci of potential genetic variation[31] (as well as differentiation between male and female) were examined. However, the Service was planning to move shortly to looking at 13 or 16 loci, in common with similar agencies in other countries (Q 125).

Advances in genetic and molecular technology

4.25 Most of the advances outlined in the preceding paragraphs will rely on developments in the enabling technology.

4.26 As the Sanger Centre noted, sequencing has become cheaper and more widely available (p 88). According to the Academy of Medical Sciences, the trend seemed set to continue (p 1). Professor Bell looked forward to developments in high throughput sequencing within 10 years which would allow the rapid sequencing of an individual's entire genome (Q 341).

4.27 The British Heart Foundation expected micro-array or other technologies to become available which would permit recognition and comparison of up to 50,000 SNPs used as markers of functional variants that may be responsible for the inherited components in disease susceptibility (p 27). As indicated in paragraph 4.14, SNPs may also prove invaluable in the interpretation and application of findings from post-marketing surveillance of the safety of medicines. Dr Dexter said that data were already available on about 1.4 million SNPs (Q 72) and, as noted by SmithKline Beecham, further rapid progress could be expected within the next year or two (p 95).

4.28 Dr Dexter looked forward to substantial advances in understanding the structure and role of proteins in the body through the new science of 'structural genomics' (QQ 62 & 72). In addition, as noted in paragraph 4.10, advances in proteomics would aid understanding of disease pathogenesis in terms of protein function, and provide predictive markers for the early detection of disease.


4.29 The rapid advances in genetic technologies in recent years and the outstanding scientific achievement in sequencing the human genome have opened the way for advances in understanding the causes and mechanisms of disease, disease prevention and the development of new treatments. The application of these methodologies to forensic science has also been of great benefit in solving crime and elimination of suspects.

4.30 While some benefits are either already apparent or will be realised over the next five years, we are clear that it will take decades for the full potential of the step change in knowledge represented by sequencing the human genome and associated work to be realised. We fear that recent publicity may have led to misplaced expectation that benefits will be realised quickly. Accordingly, we urge that the Government and all those involved in explaining this complicated science to the public should, while stressing the benefits of research on human genetic databases, ensure that the likely time scales and other potential consequences are made clear.

4.31 The United Kingdom is a leading player internationally in this field, especially through its contribution to the publicly funded international effort to sequence the human genome. Given the increasing importance that genetics will have for health care and research activity, we see it as vital for scientific, medical and economic reasons to maintain this competitive advantage.

4.32 The United Kingdom is ideally placed to continue at the forefront of developments in genetic research and the understanding, treatment and prevention of human disease. This is because of its population size and diversity, its long tradition of carrying out large-scale population-based research, the unique resource of the NHS and the strength of its pharmaceutical industrial base. An additional important factor is that the funding from Government and industry in this area has been amplified by major contributions from the charitable sector. Indeed, it is thanks to the very substantial contribution from The Wellcome Trust in terms of both finance and leadership, that the United Kingdom is a world player in this field.

4.33 Long-term epidemiological studies will be crucial in helping to unravel the links between genetic information, environment and lifestyle in the causation of human disease. We applaud the efforts of the MRC, The Wellcome Trust and the Department of Health to establish a large national cohort to study the interactions of genetic and lifestyle factors in the occurrence of disease. We recommend that the Government should provide sufficient earmarked resources to the MRC and the Department of Health to ensure that the support and infrastructure required for this important initiative are in place.

23   Peltonen L, McKusick VA. "Dissecting human genes in the postgenomic era", Science 2001; 291: 1224-1229. Back

24   Nature 2001, 409, 913. Back

25   For example, metabolism of the anti-hypertensive drug debrisoquine depends on one of the P450 family of genes on chromosome 22 known as CYP2D6. Back

26   "Pharmacogenetics and future drug development and delivery", Lancet 2000; 355: 1358-61 Back

27   "Pharmacogenetics and the practice of medicine", Nature 200; 405: 857-865. Back

28   "Pharmacogenetics and future drug development and delivery", Lancet 2000; 355: 1358-61. Back

29   As defined in the Police and Criminal Evidence Act, a non-intimate sample is a sample of hair other than pubic hair, a sample taken from a nail or under a nail, a swab taken from part of a person's body, including the mouth (but not any other body orifice), saliva, a footprint or similar impression. Blood samples, semen or other tissue fluids, urine or pubic hair count as intimate samples (Dr Jill Tan of the Home Office, QQ 112 & 113). Back

30   Based on analysis of repetitive segments of DNA - 'short tandem repeats' (Dr Werrett of the FSS, Q 115). Back

31   In non-coding parts of the genome (Dr Werrett, Q147). Back

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