【微评论】用同样的实验动物,同样的数量,做90天实验证明转基因安全的结论成立,其产品大量倾销到中国;而做720天证明转基因不安全的结论不成立,反被撤稿。这是一种什么力量在推动呢?当前的科学、科学家、科学杂志,还能够有科学独立精神吗?田松教授发出“警惕科学,警惕科学家”的警告,这里还要加上“警惕科学杂志”的警告。科学杂志能够保持中立吗?为什么前面发表了,后面又撤稿?这不是自己打自己的嘴巴吗?所谓国际顶尖刊物上被质疑有问题的论文,如砷基生命的论文,都不撤稿,为什么对这篇影响因子并不太高的文章撤稿呢?法国科学团队的实验动了谁的神经,看其本人的声明吧。 “转基因玉米致癌”论文作者塞拉利尼发表声明 来源:新华网等 | 作者:记者 | 点击:943 | 时间:2013-11-30 10:51:06 http://www.szhgh.com/article/transgenes/201311/38479.html 2012年9月,法国研究人员在国际学术期刊《食品和化学毒物学》杂志(FoodandChemicalToxicology)上发表转“基因玉米致癌”论文,一度引发公众对转基因作物的恐慌,并且成为部分人士反对转基因食品的重要证据。但是,也遭到某些人的质疑。11月29日,《食品和化学毒物学》杂志出版方爱思唯尔集团(Elsevier)28日在美国宣布,由于研究方法和结论皆存在严重问题,决定撤除这篇论文。对此,塞拉利尼团队发表声明,称将坚持自己的结论。声明说, 以往的研究发现凡是显示转基因农作物有负面效果的,都会被监管者从实验到统计方法做严格的重审,凡是声称转基因农作物安全的研究,都被照单接受。只要是没有报告负面效果的研究,都被接受为“安全”的证明,无论他们的研究方法有何种不足(被认为无关紧要)。 “转基因玉米致癌”论文被撤稿 塞拉利尼发声明 顾秀林在其博客中发布了塞拉利尼团队声明的中英对照本(2013-11-28)。并希望严建兵教授袁越先生以及差一点乐得发疯的挺转派们来一个真正的科学批判。乌云遮天难持久,科学骗人难善终。转基因用于农业之邪恶,我们大家心里其实都明明白白。 以下是塞拉利尼团队的声明: 我们是FCT一年多前发表的论文的作者,关于农达和耐受农达的转基因生物的事(塞拉利尼等2012) 。 对于同样的质疑, 我们已经在同一个刊物上回应过(塞拉利尼等,2013),即:作为正常的科学辩论,仅仅由于实验鼠品系的选择和数量的原因,就判定研究结果“结论不完整”,这是不能接受的。我们坚持我们的结论。我们早已公布了对相同的质疑所做的回答,但至今没有见到对我们的任何回应(塞拉利尼等,2013) 。 We, authors of the paper published in FCT more than one year ago on the effects of Roundup and a Roundup-tolerant GMO (Séralini et al., 2012), and having answered to critics in the same journal (Séralini et al., 2013), do not accept as scientifically sound the debate on the fact that these papers are inconclusive because of the rat strain or the number of rats used. We maintain our conclusions. We already published some answers to the same critics in your Journal, which have not been answered (Séralini et al., 2013). 关于实验大鼠品系 同一个大鼠品系,被用在研究致癌性和慢性化学毒理学的美国国家毒理学项目中(King-Herbert et al., 2010)。SD大鼠是常规性用于毒理和致癌效果实验中的动物,其中有孟山都公司的90天实验,被当做批准NK603转基因玉米应用的依据,其他转基因农作物也是这样做的 (Sprague Dawley rats did not came from Harlan but from Charles-River) (Hammond et al., 2004; Hammond et al., 2006a; Hammond et al., 2006b). Rat strain The same strain is used by the US national toxicology program to study the carcinogenicity and the chronic toxicity of chemicals (King-Herbert et al., 2010). Sprague Dawley rats are used routinely in such studies for toxicological and tumour-inducing effects, including those 90-day studies by Monsanto as basis for the approval of NK603 maize and other GM crops (Sprague Dawley rats did not came from Harlan but from Charles-River) (Hammond et al., 2004; Hammond et al., 2006a; Hammond et al., 2006b). 这里有一个简明的初步的文献清单,表明在同行评审的杂志上SD大鼠被用在36个月的实验如(Voss et al., 2005) or in 24-month studies by (Hack et al., 1995), (Minardi et al., 2002), (Klimisch et al., 1997), (Gamez et al., 2007).,其中有一些文章就发表在FCT上。 A brief, quick and still preliminary literature search of peer-reviewed journals revealed that Sprague Dawley rats were used in 36-month studies by (Voss et al., 2005) or in 24-month studies by (Hack et al., 1995), (Minardi et al., 2002), (Klimisch et al., 1997), (Gamez et al., 2007).Some of these studies have been published in Food and Chemical Toxicology. Number of rats, OECD guidelines 实验动物数量与OECD实验规范 OECD 实验规范:第408条,关于90天实验,第452条关于慢性毒性试验,第453条关于综合致癌性/慢性毒性试验,都要求用20只动物为一组(1981和2009的规定都这样要求),尽管可以用10只动物的实验就能取得生物化学参数。我们做的是长期毒性研究而不是致癌性研究,从一开始就不是这样设想的。根据常规10只动物一组已经足够在生物化学水平上进行研究,我们测量的参数数量是非常大的 。 OECD guidelines (408 for 90 day study, 452 chronic toxicity and 453 combined carcinogenicity/chronic toxicity study) always asked for 20 animals per group (both in 1981 and 2009 guidelines) although the measurement of biochemical parameters can be performed on 10 rats, as indicated. We did not perform a carcinogenesis study, which would not have been adapted at first, but a long-term chronic full study, 10 rats are sufficient for that at a biochemical level according to norms and we have measured such a number of parameters! 在我们的实验中,性激素干扰的参数以及其它参数对于解释一年之后的严重后果是充分的。我们采用的OPLS-DA统计方法是最适宜的。关于肿瘤和动物死亡,时间效果以及每只动物的平均肿瘤数量都必须被纳入分析。在风险研究中出现的每一个迹象,都必须被充分重视。 孟山都公司的研究用了同样的大鼠品系,每组仅10只衡量20个参数,就得出同一种NK603转基因玉米“安全”的结论,而且他们的实验只做了3个月 (Hammond et al., 2004) The disturbance of sexual hormones or other parameters are sufficient in themselves in our case to interpret a serious effect after one year. The OPLS-DA statistical method we published is one of the best adapted. For tumours and deaths, the chronology and number of tumours per animal have to be taken into account. Any sign should be regarded as important for a real risk study. Monsanto itself measured only 10 rats of the same strain per group on 20 to conclude that the same GM maize was safe after 3 months (Hammond et al., 2004). The statistical analysis should not be done with historical data first, the comparison is falsified, thus 50 rats per group is useless 统计分析不应该先做历史数据,用这个方法做比较研究是错误的,用每组50只动物做研究是无意义。 采纳历史数据会把健康风险评估变成研究造假,因为食谱中的材料已经受到化学污染(by dibenzo-p-dioxins and dibenzofurans (Schecter et al., 1996)和汞污染(Weiss et al., 2005),镉污染,铬污染等,污染的程度足以改变动物肝脏和肺脏的基因表达,足以扰乱基因分析(Kozul et al., 2008)。以往的食料中还发现农药和增塑剂污染,污染来自箱笼或者水(Howdeshell et al., 2003)。历史数据也有来自可能食用了转基因的动物,很多地方的鼠粮中的确发现了转基因成分。这一切都与污染水平相关,我们已经在实验大鼠和对照组大鼠中检测到这些问题。 The use of historical data falsifies health risk assessments because the diet is contaminated by dibenzo-p-dioxins and dibenzofurans (Schecter et al., 1996), mercury (Weiss et al., 2005), cadmium and chromium among other heavy metals in a range of doses that altered mouse liver and lung gene expression and confounds genomic analyses (Kozul et al., 2008). They also contained pesticides or plasticizers released by cages or from water sources (Howdeshell et al., 2003). Historical data also come from rats potentially fed on GMOs, some animal pellets in the world do indicate that. All that corresponds to the contamination levels for which we have detected some effects in our treated rats versus appropriate controls. 在历史数据中,2年SD雌性大鼠罹患乳腺纤维瘤的为13%~62%(Giknis, 2004),但在我们的实验中对照组的发病率要低得多,这才是真正的对照,而我们的实验鼠发病率比对照组高很多,这使得我们的研究结果有显著性。动物的死亡率也是这样。 2-year historical data mammary fibroadenoma rate from Charles River SD females ranged from 13 to 62% (Giknis, 2004). We obtain a lot less in our controls, the real comparators, a lot more in treated rats. This makes our results significant, like for deaths. Double standards 双重标准 遵循同一个逻辑把塞拉利尼的实验和孟山都公司的实验做一对一的比较,如果前者被认为不足以显示危害,那么后者也不能认为证明了安全。 A factual comparative analysis of the rat feeding trial by the Séralini’s group and the Monsanto trials clearly reveals that if the Séralini experiments are considered to be insufficient to demonstrate harm, logically, it must be the same for those carried out by Monsanto to prove safety. 以往的研究发现凡是显示转基因农作物有负面效果的,都会被监管者从实验到统计方法做严格的重审,凡是声称转基因农作物安全的研究,都被照单接受。只要是没有报告负面效果的研究,都被接受为“安全”的证明,无论他们的研究方法有何种不足(被认为无关紧要)。 Basically, all previous studies finding adverse effects of GE crops have been treated by regulators with the attitude: only those studies showing adverse effects receive a rigorous evaluation of their experimental and statistical methods, while those that claim proof of safety are taken at face value. All studies that reported no adverse effects were accepted as proof of safety regardless of these manifest (but deemed irrelevant) deficiencies of their methods. 来自(Snell et al., 2012) 的一份文献概览研究可以说明这个倾向。如作者在摘要中这样说,“在这里的24项研究的结果都不建议存在任何健康危害问题…”即所有被审阅的研究都被按“票面价值”被接受和通过了。然而在文章中却指出,研究报告的作者们留下了无数缺陷,同他们指责塞拉利尼论文的问题类似,或者更严重。例如24篇中16篇(67%)文章没有交代对照组饲料是否与实验用的饲料属于同基因品种(他们的解释只是“没有采用”)。许多篇文章连讨论所用的方法都没有介绍。此外还有其他被指出的缺陷。 The review by (Snell et al., 2012) illustrates this issue. In the abstract, the authors state Results from all the 24 studies do not suggest any health hazards – taking all those studies at face value. Yet in their review, the authors find numerous weaknesses of similar or greater severity raised for the Séralini group's paper. For example, of the 24 studies they evaluated 16 (67% of all studies) did not mention using the isogenic line as control (interpreted as having not used them), many did not describe the methods in any detail, and according to the reviewers had other deficiencies too. 基于完全相同的原因,FCT应该把Hammond 等人关于耐受农达转基因玉米的那些论文全都撤回。那些论文貌似都是真正的科学讨论,发表它们只是为了给孟山都提供权威证据。 FCT should retract the Hammond et al. paper on Roundup tolerant maize for all these reasons, published for Monsanto’s authorization, or consider that each of these papers is part of the scientific debate. 最新报道:塞拉利尼“转基因玉米致癌”论文被《食品和化学毒物学》撤稿 2012年9月,法国研究人员在国际学术期刊《食品和化学毒物学》杂志(FoodandChemicalToxicology)上发表转“基因玉米致癌”论文,一度引发公众对转基因作物的恐慌,并且成为部分人士反对转基因食品的重要证据。但是,这篇论文发表后不久,就遭到科学界质疑。11月29日,《食品和化学毒物学》杂志出版方爱思唯尔集团(Elsevier)28日在美国宣布,由于研究方法和结论皆存在严重问题,决定撤除这篇论文。 当地时间11月28日,《食品和化学毒物学》的出版商荷兰爱思唯尔集团正式发布撤稿声明。声明指出,该论文现有数据不足以得出现在的结论,因此并未达到发表的标准。而此前,这篇论文发表后,仅正式提出反对意见并被《食品化学毒物学》当做“读者来信”发表的就有10多篇。 (具体见 http://www.sciencedirect.com/science/article/pii/S0278691512005637 ) 2012年9月,法国卡昂大学教授吉利斯·塞拉利尼(Gilles-Eric Seralini)发表题为《农达除草剂和抗农达转基因玉米的长期毒性》的论文。他在论文中指出,用抗除草剂的NK603转基因玉米喂养的大鼠,致癌率大幅度上升。 法国卡昂大学教授吉利斯·塞拉利尼(Gilles-Eric Seralini)在《食品与化学毒物学》发表的“转基因玉米致癌”论文被撤稿 爱思唯尔出版集团在撤稿声明中指出,上述论文发表后不久,他们就收到大量质疑的信件,对实验方法、实验对象提出质疑,甚至指出数据造假的可能。出于谨慎的原则,《食品和化学毒物学》期刊的总编辑重新审查了整个同行评议的过程,并要求作者提供实验的原始数据。虽然要求作者提供原始数据这种事并不经常发生,但这也是作者在向期刊提交论文时必须接受的义务。 爱思唯尔集团在声明中说,“没有发现欺诈或对数据有意曲解的证据”,然而,“有理由担忧”论文所提及实验中研究人员使用的实验大鼠数量和类型。 撤稿声明说:“对原始数据的深入调查表明,用如此小规模的样本数据无法得出明确结论”、“考虑到(实验中所用的)斯普拉格-道利大鼠的已知肿瘤高发生率,喂食转基因玉米组所观察到的更高的死亡率及肿瘤发生率的原因不能排除是正常自然变化”。 撤稿声明补充说,归根结底,论文的结果“尽管无不妥之处”,但是“没有说服力”,因此这篇论文达不到《食品和化学毒物学》的出版要求。 撤稿声明还说,这篇论文发表后编辑部收到多封来信,对论文描述结果的有效性、实验动物的合理使用表达关切,有些来信甚至称其中存在欺诈,多数来信呼吁撤回这篇论文。这些来信以及支持这篇论文的来信,都已和作者的回应一并发表。 “初始的评审是发挥了作用的,但是不够完美。评审委员会一直希望把评审工作做得更准确和及时,这样对读者和作者都公平。我们将把这件事当作一个教训,努力把评审工作做得更好。”这份撤稿声明如此说 英国《自然》杂志网站说,这一撤稿举动并不令人意外,《食品和化学毒物学》杂志主编本月初曾要求作者主动撤回论文,并表示如果作者拒绝,杂志方也将予以撤稿。报道还说,论文作者把撤稿形容为“丑闻”,并声称,这是因为杂志任命的一名编委此前曾在转基因农业巨头孟山都公司工作过7年。 2012年,《食品和化学毒物学》杂志刊登了法国卡昂大学分子生物学家塞拉利尼等人的一份研究报告。该报告称,将100只雄性和100只雌性大鼠分成10组,分别喂食孟山都公司的NH603转基因玉米及其他食物,两年后发现,喂食转基因玉米的实验大鼠出现肿瘤的风险高、寿命短。该论文中还附有长有乒乓球般大小肿瘤的大鼠图片。 法国卡昂大学教授吉利斯·塞拉利尼(Gilles-Eric Seralini)在《食品与化学毒物学》发表的“转基因玉米致癌”论文被撤稿。图为该论文所附的大鼠肿瘤照片。 这一结论在全球引起风波,不仅被大批科学家质疑,也遭到法国和欧洲食品安全部门的否定。法国国家卫生安全署、生物技术最高委员会和欧洲食品安全局均对塞拉利尼等人的研究展开调查,结果均认为,该研究存在诸多不足,不能作为评估转基因玉米健康风险的有效依据。 科学界质疑的焦点首先是该实验的样本太少,每组只有10只大鼠。而要在两年时间内进行严肃的肿瘤学研究,需要数个至少包括50只老鼠的小组。而且,吉利斯·塞拉利尼所使用的大鼠本身就是易患癌症,无论是否食用转基因食物,在两年内它们90%都会罹患癌症。 对此,塞拉利尼曾经回应说,许多对于毒理学和致癌机理的研究也是用这种大鼠,也是只有10只。 但是,批评者指出,他的研究显然是关于大鼠的寿命和致癌几率,并不是做毒理学和致癌机理研究,因此他使用少量的高患癌实验对象并不合适 。 在许多科学家看来,塞拉利尼论文中所呈现的患癌率和寿命的变化,更多是自然产生的,但是,而作者在结论中却刻意选取了有利于支持转基因致癌的数据。其实,在他的实验数据中,食物中转基因玉米占33%的雄鼠寿命,比食物中转基因玉米占11%的雄鼠和未食用转基因食物的雄鼠寿命都要长。 综合新华网、顾秀林博客等消息。
在 前文 我提到一个加拿大小组做的小鼠脑血管结构的基础工作。这篇文章聊聊另一篇一个德国小组做的一组精巧的小鼠脑血管阻断与血管增生实验。 小鼠头脑供血如人一样,由两根颈动脉(IA)与两根椎动脉(VA)供血。德国普朗克学院的Busch等人做了这样一个实验,他们阻断两根VA及一根IA,再观察剩下一根的IA的生理变化(最右边示意图)。 他们发现,实验小鼠大都活下来。那么剩下的唯一一根IA必然负担整个脑部的供血,由Willis环传递。相应的,那根IA因为要负担比常量多得多的流量,所以管径变粗,管壁变薄: 看右边的IA明显变粗: 三根脑血管阻断后,脑供血整体减少。同时刺激毛细血管增生,减少脑缺血风险。下图为histological分析,及biomarker Ki-67与ED-1在血管壁内层及外层的增加,为明显血管增生证据。 是一篇由实验到内容都漂亮的好文。 参考文献: H. Busch, I. R. Buschmann, G. Mies, C. Bode, and K. Hossmann, Arteriogenesis in Hypoperfused Rat Brain, J Cereb Blood Flow Metab , vol. 23, no. 5, pp. 621-628, May. 2003.
在以大鼠为研究对象的动物实验中,会有一些涉及到大脑脑区定位的问题,如大鼠造模时脑内给药位置的定位,大鼠脑内某一核团电刺激时的定位。这时,若论文有这方面内容出现时,应在方法部分体现出定位依据(即《大鼠脑立体定位图谱》),补充应有文献应注意要有文献的支持。 范例: ● 以20%乌拉坦5 mL/kg腹腔麻醉,固定在脑立体定位仪上,行常规开颅术及脑立体定位术,并维持体温37 ℃左右,保持呼吸道通畅。为避免刺激电极与记录电极发生碰撞,按。。。大鼠脑图谱 ,将刺激电极(同心圆电极NEX100,外径0.25 mm)由右向左倾斜8度插入脑内STN(坐标为AP -3.8 mm, R 2.5 mm, D 7.6 mm)。 ● 用4%水合氯醛(0.75 mL/100 g)麻醉大鼠,在无菌条件下经脑立体定位仪行双侧海马定位注射(前囟后3.3 mm,旁开1.8 mm,颅骨表面下3.5 mm) 10 g A1-40建立AD动物模型。 ● 将大鼠固定于立体定向仪。依据大鼠脑立体定位图谱 ,取两耳中点始向后3.0 cm头皮正中切口,暴露矢状缝、前囟及右侧颅骨表面,将微量加样器(Ependoff 德国)抽取质量浓度为1g/L pCDNA3.1(+)/Ngb,选择注射点1 (距矢状缝右侧3.8mm、前囟前1.7 mm 处),于此处以牙钻钻透颅骨,移动立体定位仪垂直标尺,将微量加样器针头置于该骨孔内深2.8 mm。以速率为0.25 L/min注入3.3 mL pCDNA3.1(+)/Ngb,注射结束后5 min撤出微量加样器,以骨蜡封闭骨孔。 ● 大鼠经4%水合氯醛10 mL/kg腹腔注射麻醉后,俯位固定于脑立体定位仪上,按。。。大鼠脑图谱 确定右侧纹状体(STR)部位(A点坐标为 AP 1.7 mm, R 2.0 mm, H 5.4 mm;B点坐标为 AP -0.4 mm, R 4.0 mm, H 6.0 mm)。在STR 2位点所对应颅骨处各钻一直径为1 mm的骨窗。用5 L微量注射器分别向2位点注入6-OHDA(用含1%维生素C的无菌生理盐水配制而成,浓度为4 g/L,4 ℃避光保存)2 L,注射速度为1 L/min,留针10 min,再以1 mm/min的速度缓慢退针,缝合皮肤,腹腔注射氨苄西林8万单位,术后置于笼内正常光照、饮食饲养。 下面我再介绍一下由澳大利亚新南威尔士大学的Paxinos教授编写的The Rat Brain in Stereotaxic Coordinates--Compact Third Edition(《大鼠脑立体定位图谱》(第三版)),其在INTRODUCTION部分简要介绍了为何要建立大鼠脑立体定位图谱,以及该图谱发展历程,以及其的应用的主要技术手段 。(本来还想附上该图谱原版PDF,无奈上传多次,无法完成,只好放弃 ) There are many reasons why the rat is the most commonly selected subject for research in mammalian neuroscience. First, rats are the right size: neither too small for accurate stereotaxic localization of discrete brain areas nor too large for cost-effective laboratory management. Second, rats are generally hardy animals and are resistant to infections. Third, a number of inbred strains are available commercially; so, animals of consistent size can be used for stereotaxic procedures. 大鼠作为最哺乳动物神经科学研究领域最常用到的动物的原因有许多:(1)大鼠尺寸适中,对于个别脑区的精确的定位来说不至少太小;个头又不至于太大,从而花费太多的科研经费。(2)大鼠抗感染能力较强。(3)大量的近交系大鼠在商业上已经比较成熟,可买到。 When the first edition of The Rat Brain in Stereotaxic Coordinates was published in 1982, it was the first atlas to be based on the flat-skull position. It offered a choice of bregma, lambda, or the midpoint of the interaural line as the reference point. Although the coordinates were developed from study of adult male Wistar rats with weights ranging from 270 to 310 g, the atlas can be successfully used with male or female rats, with weights ranging from 250 to 350 g (Paxinos et al., 1985). 《大鼠脑立体定位图谱》(第一版)于1982年出版,其是第一部基于颅平面的图谱。该图谱应用的定位坐标点涉及前囟、人字点、两耳连线的中点。这些坐标点从最开始时只适用于成年雄性Wistar大鼠(体质量270-310 g), 发展至适用于不同性别、体质量250-350 g的大鼠。 The present atlas presents 78 diagrams of coronal sections of the brain, at intervals that average 0.25 mm. The sections were cut from unfixed brains that were frozen. The diagrams in this atlas were originally based on the study of Nissl- (cresyl violet) and acetylcholinesterase- (AChE) stained sections (see coronal photographic plates of Paxinos and Watson, 1986). The mapping of the sections for this compact third edition was assisted by the use of our sections showing the distribution of a number of antibody-based and enzyme-based stains (parvalbumin, calbindin, calretinin, SMI-32, tyrosine hydroxylase, and NADPH diaphorase). A comprehensive atlas based on chemical markers will be published by Academic Press (Paxinos et al., in press ). 《大鼠脑立体定位图谱》(第三版)展现了大鼠冠状切面的78张示意图(附有详细图解),每张切片平均间隔0.25 mm。所用切片为冰冻切片,切片染色方法为尼氏染色(焦油紫)和乙酰胆碱酯酶染色,另外还应用了免疫组化染色方法。
Rats and mice: what's the difference? What do the terms rat and mouse mean? Differences between Norway rats and house mice How can I tell rats and mice apart? Quiz: rat or mouse? History and evolution of the Norway rat and the house mouse Common ancestry of the Norway rat and house mouse Brief history of the house mouse Brief history of the Norway rat and black rat Are rat-mouse hybrids possible? Mouse-killing behavior in rats: muricide What do the terms rat and mouse mean? Rat and mouse are actually not scientific classifications. These words are common names for rodents that look alike to the casual eye. Rat is used to describe medium-sized rodents with long thin tails. There are many species of rodent that are called rats -- kangaroo rats, cotton rats, Norway rats, black rats, African pouched rats, naked mole rats, wood rats, pack rats, Polynesian rats, and many others. These different rodent species may not be closely related to each other at all! Mouse is used to describe tiny, sparrow-sized rodents with long thin tails. As with rats, there are many species of rodents called mice which may or may not be closely related to each other: house mice, field mice, deer mice, smoky mice, spiny mice, and dormice are all called mice. So, which rats and mice are you talking about? Generally, people are referring to the domestic or pest rats and mice, which means Norway rats ( Rattus norvegicus ), black rats ( Rattus rattus ), and house mice ( Mus musculus ). Differences between Norway rats and house mice Norway rats and house mice belong to different species. A species is a group of related individuals or populations which are potentially capable of interbreeding and producing fertile offspring. So Norway rats and house mice belong to different species and cannot interbreed . Humans and orangutangs, chipmunks and red squirrels, bottlenosed dolphins and killer whales, all belong to different species. Norway rats and house mice are related, however. They descend from a common ancestor that lived millions of years ago -- how long ago is currently under debate, with estimates ranging from 8 to 41 million years ago. That estimate will probably become more precise over time. The descendants of that common ancestor diverged into different species, among which are Norway rats and house mice. Norway rats and house mice now have many genetic, reproductive, developmental, morphological and anatomical differences. The list below is not exhaustive, but for those with a casual interest it should get you started: Genetic differnces : Norway rats have 22 chromosome pairs, house mice have 20 (see Levan 1991). Norway rats have 2.75 million base pairs while mice have 2.6 million (humans have 2.9). About 90% of rat genes have counterparts in the mouse and human genomes (Rat Genome Sequencing Consortium 2004). See Burt et al. 1999, Grutzner et al. 1999, and Watanabe et al . 1999 for more. Growth differences: In general, Norway rats develop more slowly than house mice. For example, Norway rat gestation is slightly longer (21-24 days) than house mouse gestation (19-20 days). Norway rats lactate for about 3 weeks, house mice for 2 weeks. Both species are born naked and blind, but Norway rats open their eyes at 6 days, they are fully furred at 15 days. House mice open their eyes at 3 days, have fur at 10 days (etc.). Anatomical differences: Norway rats have 6 pairs of nipples, house mice have 5 pairs. Morphological differences: Norway rats are larger, heavier and longer than house mice (Norway rat: 350-650 grams, 9-11 inch bodies and 7-9 inch tails; house mice: 30-90 grams, 3-4 inch bodies and 3-4 inch tails). Correlated with this larger size, Norway rat body parts are larger than those of the house mouse -- rats have larger ears, feet etc. The heads of Norway rats are heavy, blunt and chunky, house mouse heads are small and sharply triangular with pointed muzzles. Note, however, that Norway rats have smaller ears relative to their heads than house mice. Sign differences: Due to their larger body size, rat feces are larger than mouse feces (also see differences in rat and mouse sign from a pest management perspective). Life-size drawing of mouse and rat feces. How can I tell Norway rats and house mice apart? Adult rats and mice Adult mice are much smaller than adult rats (Fig. 1). Adult mice weigh about 30 grams, and fancy mice tip the scales at about 50 grams. Adult mice have bodies that are 3-4 inches long with 3-4 inch tails. Adult rats are far heavier and longer: they can weigh ten times as much, averaging 350-450 grams for females and 450-650 for males (with an overall range of 200-800 grams). They have 9-11 inch long bodies and 7-9 inch tails ( ref ). Figure 1. Drawing showing the relative size of rats and mice Young rats vs. adult mice Young, weaned rats are still larger than adult mice, weighing around 100 grams at six weeks. However, to the casual observer, very young rats and adult mice can be difficult to tell apart. Here's what to look for: baby rats will have more juvenile proportions than adult rodents. Their heads and feet will be large relative to their bodies, their faces will be stubby and blunt with wide noses. Adult mice, on the other hand, will have adult proportions: a small, triangular head with a small nose and little delicate feet as compared to the body. In addition, mouse ears are very large relative to their heads, rat ears are smaller relative to their heads. Rats also have thicker tails than mice. Feature Baby Rat Adult Mouse Head short, stubby, broad, large relative to body small, triangular, small relative to body Muzzle large and blunt with wide muzzle narrow with sharp muzzle Ears ears are small relative to the head ears are large relative to the head Tail thick thin Tail/body ratio Tail shorter than body Tail same length/longer than body Feet Large relative to body, especially the hind feet Small relative to body Weight around 100 grams at 6 weeks, 200 grams at 8 weeks 30-50 grams 6 week old rat Adult mouse Quiz: Rat or Mouse? Take this quiz to test your ability to tell photos of rats and mice apart. History and evolution of the Norway rat and the house mouse Common ancestry of the Norway rat and house mouse True rodents first appear in the fossil record at the end of the Paleocene and earliest Eocene in Asia and North America, about 54 million years ago. They are widely considered to have originated in Asia (Meng et al. 1994). These original rodents were themselves descended from rodent-like ancestors called anagalids, which also gave rise to the Lagomorpha, or rabbit group. Murids ( Muridae ), the family that gave rise to present-day Norway rats, house mice, hamsters, voles, and gerbils, first appeared during the late Eocene (around 34 million years ago). Modern murids had evolved by the Miocene (23.8-5 mya) and radiated during the Pliocene (5.3-1.8 mya) (for more, see Introduction to the Rodentia ). The Norway rat and the house mouse had a common murine rodent ancestor. How long ago that common ancestor lived is a matter of debate, however. The fossil record indicates that the most recent common ancestor of Norway rats and house mice lived about 8-14 million years ago (Jacobs and Pilbeam, 1980). Geneticists, however, estimated that their most recent common ancestor lived about 41 million years ago (Kumar and Hedges, 1998). Brief history of house mice The ancestors of the house mouse ( Mus musculus ) lived in the steppes of present-day Pakistan. Ten thousand years ago, at the end of the last ice age, neolithic farmers moved from the Fertile Crescent into the steppes of Pakistan, and these small rodents found a delightful new source of food and shelter. When humans migrated away from the steppes to colonize other areas, mice went along as stowaways in the humans' carts and later, their ships. House mice arrived in the new world in the 16th century, arriving with explorers and colonists. Mice went everywhere with humans, living in and around their houses, a human-dependent association called commensalism . Today, commensal house mice live in and around human dwellings on every continent, in every climate. Today, commensal house mice are divided into four subspecies: M. musculus bactrianus are the descendants of the original, ancestral house mice first encountered by our neolithic ancestors. They live in India, Pakistan and Afghanistan. M. musculus castaneus lives in Southeast Asia. M. musculus musculus lives in Russia and western China, and M. musculus domesticus lives in Europe, from whence it traveled to the Americas, Australia, New Zealand, and Africa with the colonists. Domestication : Domestic mice originated from stocks captured in China, Japan and Europe and developed into fancy mice. These fancy mice were found in pet shops in the 20th century, and were developed into laboratory mouse strains. Fancy mice are primarily descended from M. musculus domesticus , with a little admixture of the other three subspecies. As such, domestic mice do not represent one of the single subspecies, but are a mixture of all four. ( Silver, 1995 ). Brief history of Norway and black rats See separate article, History of the Norway rat . Are rat-mouse hybrids possible? See separate articles, are rat-mouse hybrids possible? and the hybridization page. Mouse-killing behavior in rats: muricide Rats can, and do, kill mice, a behavior known as muricide . Muricide is a form of predatory behavior: rats hunt, kill and eat mice. How common is muricide? Karli (1956) found that about 70% of wild rats and 12% of domestic laboratory rats kill mice. Male and female rats are equally likely to kill mice. Similarly, Galef (1970) found that 67% to 77% of captive born wild rats kill mice. Description of muricide Muricide is a stereotyped behavior, performed in much the same way each time: the rat chases the mouse around the cage and bites it using its sharp front incisors, usually aiming for the mouse's head, neck, or upper back. The first bite is frequently fatal, but the mouse may delay the rat's attacks by defending itself (by rearing up and boxing with its front paws or laying on its back). Eventually, however, the rat delivers a fatal bite. Mouse-killing behavior is very rapid, lasting only a few seconds (Hsuchou et al. 2002). The preferred area to bite is the back: out of 671 mice killed by rats, 89% were bitten on the spinal cord (specifically: 65% neck, 13% thoracic, 11% lumbar). Only 7% were bitten on the belly and 4% were bitten on the head (Karli 1956). Do rats eat the mice they kill? Karli (1956) found that all mouse-killing rats (wild or domestic) consumed part of the mice they killed. Specifically, out of 683 mice killed by rats, after 7 hours 25% of the mice had been entirely eviscerated (brain, thoracic and abdominal viscera), 67% had been partially eviscerated, and only 8% had not been eaten. Wild rats tended to start eating at the spot where they had bitten the mouse, which is usually the neck. They gradually opened the thorax and consumed the thoracic viscera, then proceeded to the liver. In contrast, domestic rats went right to the brain, opening the skull and consuming all or part of the brain, no matter what killing method had been used (Karli 1956). Exogenous and endogenous influences Mouse-killing is a complex behavior involving several neurotransmitter systems (Miachon et al . 1997, Onodera et al. 1981, Tadano et al. 1997, Ueda et al. 1999, Vergnes and Kempf 1982, Yamamoto et al. 1982), neural systems (Hull and Homan 1975, Spector et al. 1972) and hormonal systems (Miachon et al. 1995; Rastegar et al. 1993). Mouse-killing is also affected by by rearing (Garbanati et al. 1983), environmental conditions (Garbanti et al. 1983, Giammanco et al. 1990), social conditions (Eisenstein and Terwilliger 1984), diet (Bac et al. 2002, Onodera et al. 1981), learning (Tingstrom and Thorne 1978). Rats are more likely to kill mice at night than during the day (Russel and Singer 1983). Mouse-killing is affected by hunger , too: rats kill mice more when they are hungry (Malik 1975) and at times when they are normally inclined to eat food (Russel et al. 1985). Rats may start killing mice when they are starving, but stop when they are given plenty of food (Karli 1956). Familiarity with mice also plays a role: rats reared with mice tend not to kill mice as adults. Specifically, Galef (1970) found that 67-77% of captive born wild rats kill mice. However, if captive born wild rats are raised with a mouse from weaning to age 3 months, none of them kill the mice they're familiar with. When presented with an unfamiliar mouse, only 7% of the mouse-reared rats killed it. Response of mice to rats Rat odor is stressful to mice and has an effect on their behavior and reproduction. In fact, rat odor is sometimes used as a predator odor to study anxiety and antipredator behavior in mice. Specifically, domestic and wild-stock mice who are exposed to a conscious or anesthetized rat tend to flee, and if prevented from fleeing, they show defensive or attack behavior (Griebel et al. 1995, Blanchard et al. 1998). Mice housed in the same room as rats tend to be more stressed than mice housed without rats (Calvo-Torrent et al. 1999). Mice who can smell rat urine take ten times longer to start eating a treat than mice who cannot (Merali et al 2003). Mice who were exposed to rat urine for just a few minutes startle more afterwards, even up to two days after the rat urine exposure (Hebb et al. 2003). Pregnant mice exposed to rat urine produce fewer litters than mice who were not exposed (de Catanzaro 1988). http://www.ratbehavior.org/RatsMice.htm