Bio@SNS Laboratory, Scuola Normale Superiore, 56126 Pisa, Italy.
Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):4877-85. doi: 10.1073/pnas.1217586110. Epub 2013 Mar 20.
In a PNAS Classic Article published in 1960, Rita Levi-Montalcini offered formal and conclusive proof that endogenous NGF was responsible for the survival of sympathetic neurons in vivo. Thus ended an experimental tour de force lasting a decade, starting with the demonstration that a humoral factor, produced from a tumor transplanted in a chicken embryo, was responsible for stimulating outgrowth of nerve fibers from sympathetic and sensory neurons. From a more general methodological point of view, this work provided a breakthrough in the quest to achieve targeted loss of function and experimentally validate the function of biological molecules. Finally, this work provided an example of the ablation of a specific neuronal subpopulation in an otherwise intact nervous system, an immunological knife of unsurpassed effectiveness and precision. The novelty and the importance of the PNAS Classic Article is discussed here, collocating it within the context of the particular moment of the NGF discovery saga, of Rita Levi-Montalcini's scientific and academic career, and of the general scientific context of those years. This seminal work, involving the use of antibodies for phenotypic knockout in vivo, planted seeds that were to bear new fruit many years later with the advent of monoclonal antibodies and recombinant antibody technologies.
在 1960 年发表的一篇 PNAS 经典文章中，Rita Levi-Montalcini 提供了正式而确凿的证据，证明内源性 NGF 负责体内交感神经元的存活。这标志着一项持续了十年的实验壮举的结束，该壮举始于证明一种体液因子，由移植到鸡胚中的肿瘤产生，负责刺激交感神经和感觉神经元的神经纤维生长。从更普遍的方法论角度来看，这项工作在实现靶向功能丧失和实验验证生物分子功能方面取得了突破。最后，这项工作提供了一个在完整神经系统中消除特定神经元亚群的例子，这是一种具有无与伦比的有效性和精确性的免疫刀。本文在这里讨论了这篇 PNAS 经典文章的新颖性和重要性，将其置于 NGF 发现传奇故事的特定时刻、Rita Levi-Montalcini 的科学和学术生涯以及这些年的一般科学背景中进行了讨论。这项开创性的工作涉及在体内使用抗体进行表型敲除，为多年后单克隆抗体和重组抗体技术的出现播下了新的果实。
