Lockshin Richard A
Department of Biological Sciences, St John 's University, 8000 Utopia Parkway, Queens, NY, 11439, USA.
J Soc Biol. 2005;199(3):169-73. doi: 10.1051/jbio:2005017.
Cell death was observed and understood since the 19th century, but there was no experimental examination until the mid-20th century. Beginning in the 1960's, several laboratories demonstrated that cell death was biologically controlled (programmed) and that the morphology was common and not readily explained (apoptosis). By 1990 the genetic basis of programmed cell death had been established and the first components of the cell death machinery (caspase 3, bcl-2 and Fas) had been identified, sequenced, and recognized as highly conserved in evolution. The rapid development of the field has given us substantial understanding of how cell death is achieved. However, capitalizing on our knowledge for therapeutic purposes requires us to learn much more about how a cell commits to death, as well as recognizing that apoptosis may be the most common and efficient means of death, but that there are alternative pathways that can result in cell death even when the conventional pathway is blocked. Interestingly enough, many of the arguments and missteps in the history of the field were anticipated by Claude Bernard, and his warnings and recommendations remain valid today.
自19世纪起,细胞死亡就已被观察和了解,但直到20世纪中叶才有了实验研究。从20世纪60年代开始,几个实验室证明细胞死亡是受生物控制(程序性)的,而且其形态常见且难以轻易解释(凋亡)。到1990年,程序性细胞死亡的遗传基础得以确立,细胞死亡机制的首批成分(半胱天冬酶3、bcl-2和Fas)已被鉴定、测序,并被认为在进化过程中高度保守。该领域的快速发展让我们对细胞死亡的实现方式有了相当深入的了解。然而,要将我们的知识用于治疗目的,就需要我们更多地了解细胞是如何走向死亡的,同时要认识到凋亡可能是最常见且高效的死亡方式,但即便传统途径受阻,仍存在其他可导致细胞死亡的途径。有趣的是,该领域历史上的许多争论和失误克劳德·伯纳德都曾预见到,他的警告和建议如今依然有效。