Meeting the challenge of genetic advanceBMJ 1998; 316 doi: https://doi.org/10.1136/bmj.316.7131.570 (Published 14 February 1998) Cite this as: BMJ 1998;316:570
Requires rigorous navigation between laboratory, clinic, and society
- Mike Gill, Director of public health and health policy,
- Tessa Richards, Associate editor
See p 618
Advances in molecular genetics over the past decade have been remarkable. Soon the entire human genome will have been sequenced and most of the genetic loci associated with human disease identified. These advances have greatly enhanced understanding of disease mechanisms and begun to explain why the clinical course of common disorders such as diabetes, asthma, and rheumatoid arthritis is so variable, as Bell discusses in the first of four articles on the broader implications of the new genetics (p 618).1 In future presymptomatic population based genetic testing for common late onset disorders such as Alzheimer's disease2 and colon cancer may become widespread and bring important health benefits. Genotyping may become part of routine investigations to help clinicians tailor drug treatment effectively.
But in what has been dubbed the “post-genome” era, increasing attention is now being paid to the limitations as well as the potential of DNA based genetic tests. The ability to detect genes greatly exceeds our understanding of what they do. Even in the simple Mendelian disorders the relation between the DNA sequence of a gene and the corresponding phenotype is far from clear. In late onset conditions, such as coronary heart disease and diabetes, where genetic, social, biological, and environmental factors interact over time, predicting the clinical importance in a given patient of several different mutations of low penetrance genes is very difficult.3
Some mutations—for example those associated with type 1 diabetes—have a high population frequency and may therefore be protective. Early optimism about the potential value of screening for breast cancer genes has been replaced by recognition that the prognostic meaning of the mutations is unclear4 and that taking action on “gene based statistical prophecies” may not be in patients' interests.5 In Britain the Human Genetics Advisory Commission has concluded, “It is unlikely that actuarially important genetic predictions of common causes of adult death will be available and validated for some time.”6 Genetic epidemiology is in its infancy.
Whether testing will inevitably become widespread as more tests become available is uncertain. Much depends on the severity of the disease and the scope for effective treatment or prevention. Readiness to undergo testing also depends on how testing is offered and on personal, social, and psychological factors; the more well informed people are, Marteau suggests in next week's article in the series, the less likely they are to want testing.
Rigorous assessment of the benefits and costs, both economic and psychosocial, of introducing new genetic screening tests is essential, not least because information from genetic tests carry implications for families as well as individuals. The problems of testing children who are too young to give informed consent are well recognised, and there is broad agreement that predispositional testing for late onset disorders should not be done.7 Prenatal screening remains contentious because of the fine line between allowing couples to make informed choices and pressurising them to terminate affected fetuses. Some argue that the intention of much genetic research is eugenic by implication,8 and legislation in China which has made this explicit has provoked passionate controversy.9
Among the public, upbeat reporting of the identification of new genes and the ability to test for them has raised both interest and concern. Fears about discrimination by insurance companies and employers is understandable despite the introduction in America of a federal law to protect against such discrimination and in Britain reassurance from the Association of British Insurers. As studies to correlate genetic predisposition with clinical disease increase, issues of confidentiality and informed consent warrant more attention.10 The inadequate counselling and failure to obtain written consent from most subjects in a recent study of testing for the adenomatous polyposis gene is worrying, as is the fact that many doctors requesting the test did not recognise its limited predictive value.11
Failure to appreciate the complexity and limitations of genetic tests and the fact that testing may provoke rather than allay uncertainty must be tackled. The difficulty in ensuring appropriate use of tests for prostate specific antigen is instructive.12 Even a small increase in genetic testing for predisposition to common diseases will severely test the current supportive medical model with its intensive pretest counselling and post-test follow up.
Inevitably the brunt of dealing with the public's hopes and fears will fall on doctors in primary care. We urgently need to define likely service needs and how best to establish collaboration between geneticists, public health specialists, and primary care teams. Meanwhile, those engaged in genetic research have a responsibility to draw attention to the limits as well as the potential of their findings and to foster balanced media reporting. And in discussions over public policy, expert committees must fully recognise the importance of open debate.