Mysterud I
Zoologisk avdeling, Universitetet i Oslo, Blindern.
Tidsskr Nor Laegeforen. 1995 Jun 30;115(17):2114-9.
This paper contains four parts. The first focuses on The Human Genome Project (HGP). The concept of a "normal sequence" seems problematic. The second part reviews what is meant by "genetically-caused" and by "a (several) gene(s) for a trait". Genes work in concert, and it is likely that many genes together influence most complex traits. A difference in traits between two individuals, however, can be due to a difference in a single gene, as is the case for several thousand rare "genetic diseases". Such diseases were the original focus of gene therapy. Could gene therapy also be applied to more common complex traits? Diagnostic problems and the unsuccessful attempts to find a single gene difference in patients with manic depressive disorder, schizophrenia and Alzheimer's disease are discussed. Part three reviews future genetic research into complex traits and what kind of treatment can realistically be expected. It is concluded that improved diagnostics is the most likely outcome, not therapy. Part four raises arguments from the emerging Darwinian approach to medicine and states that it is far too early to even think of gene therapy. The needed knowledge about genes, behaviour and disease will not come from the one-sided genetic effort represented by HGP, and the resources should instead be invested in several different approaches to these complex issues.
本文包含四个部分。第一部分聚焦于人类基因组计划(HGP)。“正常序列”的概念似乎存在问题。第二部分回顾了“基因导致”以及“某一(些)性状的基因”的含义。基因协同作用,很可能许多基因共同影响大多数复杂性状。然而,两个个体之间性状的差异可能仅源于单个基因的差异,数千种罕见的“遗传疾病”便是如此。这类疾病是基因治疗最初关注的对象。基因治疗能否也应用于更常见的复杂性状呢?文中讨论了诊断问题以及在躁郁症、精神分裂症和阿尔茨海默病患者中寻找单个基因差异的失败尝试。第三部分回顾了未来针对复杂性状的基因研究以及实际可预期的治疗方式。结论是,最有可能的结果是诊断得到改善,而非治疗。第四部分提出了新兴的达尔文医学方法的观点,并指出现在考虑基因治疗甚至还为时过早。关于基因、行为和疾病所需的知识并非来自人类基因组计划所代表的片面的基因研究努力,相反,资源应投入到针对这些复杂问题的几种不同方法中。