最近刚参加一个学术会议，会议上一位教授空闲时间在网上溜达的时候意外发现一篇新发表在PNAS上的重量级文章：Genomic responses in mouse models poorly mimic human inflammatory diseases
      摘要如下：
   A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate                              new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic                              studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although                              acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses                              in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly                              in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R² between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority                              for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study                              human inflammatory diseases.
       文章第一段还说：Murine models have been extensively used in recent decades to identify and test drug candidates for subsequent human trials (1–3). However, few of these human trials have shown success (4–7). The success rate is even worse for those trials in the field of inflammation, a condition present in many human diseases. To date, there have been nearly 150 clinical trials testing candidate agents intended to block the inflammatory response in critically ill patients, and every one of these trials failed (8–11).
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       其实关于使用老鼠研究人类疾病的有效性一直存在不小的争议，生命体作为复杂系统，不同生物种的生物有着不同的分子网络体系并不奇怪，因此人类对于利用老鼠而建的人类疾病的研究模型设计的药物有不同于预期的反应（response）也挺正常。当然现在有实验室专门把这个当作一个课题来研究，整理大量已有的临床数据来证实老鼠模型对于模拟人类疾病（当然这篇文章针对的是炎症相关疾病）并没有太大的现实意义。
       然而这不是说用老鼠或者果蝇或者线虫做基础研究就不值得做了。利用动物模型，培养和开发新的，以复杂系统的角度出发的研究手段，还是有它的意义的。只是从动物模型直接得到的什么结果，不论论文作者还是阅读者都要一定要保持谨慎态度，不要轻易地推广到认为那些结论对于人类也适用。当然，我们理解为什么人们会有这样的一厢情愿。可惜自然就是没有那么简单，我们也不得不接受这个现实。