伟大科学家的重要错误：达尔文的遗传学
达尔文进化论的精髓，广为证明。不断出现的发对，从来没有撼动其根本。
但是，达尔文提出对遗传的想法，却有问题。
科学文献讨论，常规自然是最新文献。
查理曼但是，读史有些时候也可以有好玩、甚至有意义体会。
我想在今天组会简介达尔文对遗传的想法。
达尔文1868年在《家养动植物变异》一书讨论“泛生假说”（Hypothesis of Pangenesis）的一章。起因是我近年上《生物学思想和概念》课程时，和本科生一道读孟德尔1866年的遗传学论文。有趣的是，达尔文不仅做过类似实验，而且还脱离实验，提出过遗传理论，就是“泛生假设”。比较达尔文和孟德尔的文章，可以有多种讨论，特别是不同的科学思维方法。其中，有些问题并未过时，而很有现实意义。
孟德尔的遗传学研究，有高度的选择，而得出清晰的结果、推出明确的理论。而达尔文，将
多个现象联系在一起，提出一个假说可以同时解释这些现象。
科学研究过程中，大家遵循一个规则，所谓Occam剃刀，以最简单的理论解释实验的结果和观察到的现象。如果简单理论可以，就不用复杂理论来解释。如果用复杂理论来解释，那么复杂加复杂可以叠很多层，就很难讨论和验证。以简单理论作为基本步骤，科学虽然前进很慢，但较扎实。
Occam剃刀是经验模式，并无标准公式。比如，是用简单的理论尽量解释很多的现象，还是对于所解释的现象要有所局限、有所选择？
特尤斯1868年，达尔文把五类现象，代间遗传、发育、再生、植物嫁接、用进废退，全部联系在一起讨论，他提出的理论，把我们现在认识到的“细胞全能性”（全身很多细胞一直保持整套基因组）、和遗传规律混在一起。他的泛生论确实好像可以解释多个现象，但事后我们可以看到是不同性质和不同层次的现象，因为他求全，所以得出的反而是错误的理论。他提出生物体全身体细胞都产生泛子gemmules（后人亦称pangenes），进入性细胞中，这些gemmules的组合决定了性细胞内含，形成不同的性细胞，再产生不同的后代。在强调体细胞产生泛子的重要性时，达尔文说生成性原生质(generative protoplasm)要么不全在于
大饱眼福
生殖细胞，要么生殖细胞没有再生原生质，而是收集和选择泛子。他在讨论中甚至接受了拉马克（1744-1829）的“用进废退”，而认为泛生假说能解释用进废退（比如连续多代人工地切掉牛角），这是他的理论最可笑的部分，虽然他说很难相信，但自己也看过一个例子，当然还据其他人说。他说受外界影响的体细胞性状可以获得并通过gemmules进入性细胞而传代。达尔文在获得F2代重新出现F1代不见了的隐性性状时，仅看到现象，提出所谓“回复原理”（Principle of Reversion关于醉酒的诗句），这并非原理，而是以新名词复述现象。
孟德尔只研究代间遗传，不考虑其他现象。而且他仔细选择了实验对象，还选择了观察的性状。他明确说只研究子代一定相同于父本、或者母本的那些性状，而他知道有些性状，子代既不同于父本、也不同于母本，或者介于两者之间。这样，他得出的结果很干净，而他的理论很好地解释了他的结果。
1866年和1868鸭掌木年，两个理论发表后，他们两人在世期间，可能没人同时知道两个理论。
假设我们在当时看到孟德尔和达尔文的理论及其证据，一般并不能很简单地断定谁对。孟德尔的理论比较严谨，但他高度选择可能是优点，也恐怕导致理论不具有普遍意义。达尔文的遗传理论，解释现象较多，但怕是眉毛胡子一把抓。
在现在和未来做研究时，这样的问题，同样存在，只是一般来说，当局者迷，到以后才会恍然大悟。
如果在研究的早期，正确的选择范围和对象，可能是科学洞察力的关键之一。
达尔文当时认为体细胞的性状可以影响生殖细胞的遗传组成。后来德国生物学家魏思曼（August F. L. Weismann，1834-1914）提出germ plasma（种质）学说，种质只存在于生殖细胞中由亲代传给后代，生殖细胞可以产生体细胞，而体细胞不能产生生殖细胞，种质不受体细胞和环境影响而改变。完全摒弃了拉马克主义的基础。哈佛大学的Ernst Mayr将魏斯曼称为19世纪仅次于达尔文的进化论学者。
魏斯曼的实验很简单：他把小鼠的尾巴切掉，然后让他们生子鼠，他观察了5代，901只老鼠，没有一个后代的尾巴短了。反对魏斯曼的人会说5代不够，要更多代（而且可以无限代）的重复才能证明。但是实际上一般民间传说都是外界对一代动物影响（比如剪断猫尾巴）就遗传到下一代，所以，虽然5代实验不能代替几十代、几百代，这个结果还是完全否定了此前民间和学界不负责任的各种传说，也摧毁了获得性遗传的基础。
魏斯曼还用了人群的社会习俗作为例子：中国妇女裹脚多代并没有导致中国人小脚，而当时得代代继续裹才行；犹太儿童切割包皮没有导致犹太人天生无包皮，而得每代都环切才行。
如果从一般遗传性状上看来，以后的经验也都证明种质隔离的正确性。
但是，魏斯曼的实验很简单，而做结论 时，不仅普遍化而且层次上升了。也就是说，其结论超出了其实验结果。
比如，性状不能获得性遗传，并不能否定体细胞有可能影响性细胞内的遗传物质。我们现在重新思考，可能还有问题。在基因概念一再变化的情况下，遗传不一定要用性状来看，而可以用分子来看，比如硅藻泥装修效果图DNA、RNA、甚至蛋白质和其他分子或亚细胞器。
那么，我们是否可以重新设计实验，研究体细胞对于生殖细胞能否发生能够遗传的改变？目前热门的表观遗传学，对此有何意义？还是有其他更值得探讨的？
好像是问题。
（2010年10月25日下午，饶实验室组会）
注
在有关孟德尔的文章《孤独的天才》一文 中， 更多讨论达尔文错失正确理解遗传学的机会。
组会后学生反馈，如《当代生物学》2010年10月26日论文：
Remy J-J (2010) Stable inheritance of an acquired behavior in Caenorhabditis elegans. Current Biology 20:R877-R878.
表观遗传学可参见：Richards EJ (2006) Inherited epigenetic variation — revisiting soft inheritance. Nature Reviews Genetics 7:395-401.
魏斯曼原文见：
Weismann A (1893). The Germ-Plasm. A Theory of Heredity
/books/weismann/germ-plasm/facsimile/
达尔文的相关一章抄录如下（红色和斜体为所我加，书中达尔文的注解从略，有兴趣者可
以查阅原书）：
Darwin C (1868). The variation of animals and plants under domestication. John Murray, London.
Chapter XXVII
Hypothesis of Pangenesis
Having reflected much on some of the subjects described in the veral previous chapters, I have been driven to some hypothetical conclusions, which may perhaps be worth giving. I will in the first place enumerate the leading points;
True minal generation pass by a not much broken ries, through gemmation or multiplication by buds, through fissiparous generation and the renewal by growth of large portions of mutilated individuals, into simple continual growth. The concurrence of the two xual organs and often of two individuals is necessary in all ordinary cas of minal generation; but the now well-known cas of 'true parthenogenesis' show that the unimpr
egnated ovum, passing through the xual embryonic stages, can be developed into a perfect individual. The unimpregnated ovum also has the power of imbuing every part of the being into which it is developed with its own characters, independently of tho of the male, as we e in hybrids; especially in tho hybrids sprung from two species of which the one is strongly prepotent in the transmission of character over the other. So converly it is with the male element. It is admitted by Müller and other physiologists that there is no esntial difference in nature between the germs of an ovum and a bud; and Huxley (Transact. Linn. Soc. xxii, pp. 199, 210) has submitted to a rigid comparison the pudovum (which is of the nature of a bud) of the viviparous aphis, with the true ovum of the oviparous aphis, and can discover no difference in their minute structure. It has, however, sometimes been asrted that only individuals produced from impregnated germs acquire new characters, and that the can only be perfectly transmitted by bud-propagation; but there is no such constant difference, only one in degree and frequency. In the chapter on bud-variation we have en that not rarely individuals (phytons) produced from buds do display quite new and strongly marked characters, which can so
metimes be subquently propagated by ed; the new varieties arising from buds cannot be distinguished by any characters from minal varieties; that such new bud varieties, though generally capable of more faithful transmission by bud-propagation than minal varieties are by minal propagation, yet occasionally revert, even after a long ries of bud generations, to their priestine or parental character. This tendency to reversion in buds is one of the most remarkable points of agreement between bud and minal multiplication. There is another and still more remarkable point of agreement: we have en that a bud of one variety inrted into the stock of another variety, in some rare cas has certainly affected, as if by a kind of hybridization, adjoining buds subquently produced from the stock. If the evidence be thought sufficient, then the dingy purple Laburnam (C. adami), and tho marvellous orange trees which produce pure oranges, lemons and citrons as well as fruit of a mixed nature, have thus arin, then undoubtedly the buds of distinct species can blend together and subquently produce hybrids by budding, like tho produced from the union of the true male and female xual elements of distinct species.
季节作文
There is, I believe, one general but hardly invariable difference between minal generation and gemmation. Beings propagated by the former method, usually pass in the cour of their development from a lower to a higher grade, as we e in the metamorphosis of incts & in the concealed metamorphosis of the higher vertabrata; but this passage from a lower to a higher stage cannot be considered as a necessary accompaniment of minal reproduction, where we look to the kind of development of aphis amongst incts, or to that of all the higher vascular plants. In beings propagated by buds there is, as far as I know, no metamorphosis of this kind; that is, they do not pass first to a lower and then to a higher stage of development; unless indeed the scales surrounding the buds and bulbs of plants may be looked at as indicating such a passage. But beings produced from buds often advance in organization either during the act of their production or subquently to it, as we e in the many cas of alternate generation. For I follow tho naturalists who look at alternate generation as a process of budding, or, as in the ca of the strobila of the medusa, as one of fissiparous multiplication. In beings produced by true generation, their metamorphos, starting from
a low grade and advancing to a higher one, no doubt stand in the clost relation, either at prent or in past times, to peculiar lines of life and lead to places unoccupied in the economy of nature. Now from veral previous considerations we may conclude that there is the clost agreement in nature between a germ and a bud. The concurrence of the two xes, in the ca of the germ being only an accessory, though very general, contingent. We are naturally why the germ, which before impregnation undergoes a certain amount of development ceas to progress and perishes, unless it is acted on by the male element; and why converly the male element, which can keep alive for even four or five years in the spermatheca of female incts, likewi perishes, unless it acts on or unites with the germ, are questions which notoriously cannot be answered.
