Archive for the ‘Writing’ Category


A real hope for Down syndrome patients

September 11, 2013

This July, a research paper published in Nature shed some light on the treatment of Down syndrome, a genetic disorder due to an extra copy of chromosome 21 in human cells (1). A group in University of Massachusetts developed a strategy to silence the extra copy of chromosome 21 and restore the genes in Down syndrome cells to normal in the culture dish.

Down syndrome is a genetic disorder that affects one in 691 live births in US; it causes mental retardation, seizure, early onset of Alzheimer’s disease, heart disease, diabetes, cancer, and many others.  The British physician John Langdon Down first described the syndrome in 1866, and the French physician Jerome Lejeune first identified the cause of Down syndrome as the presence of an extra copy of chromosome 21 in cells of patients. In the past 147 years, generations of scientists have extensively studied this disorder, and gained much knowledge on the genetics, pathology, diagnosis, and management of Down syndrome. However, due to the complexity of multiple genes overexpressed from the extra copy of chromosome 21 (more than 500 genes have been identified on chromosome 21), there is no cure for this syndrome yet.

Nature is always our best teacher: we learned to use sonar navigation from bats and lighten up cells with green fluorescence protein from jelly fish. Women have two copies of X chromosomes in their cells, but only one copy is activated, with the other copy shutting down during early fetal development. This is caused by a gene on X chromosome, named X-inactive specific transcript (XIST). In 1990’s, scientists have discovered that XIST gene translocated to the other chromosomes can silence all the gene expression from that chromosome. But it is not until this year that scientists in University of Massachusetts use this strategy to shut down the genes on chromosome 21 in cells from Down syndrome.

The XIST gene was inserted into one selected location on chromosome 21 in induced pluripotent stem cells from Down syndrome patients by using a Zinc Finger protein targeting technique. The induced pluripotent stem cells were made from skin cells of a Down syndrome patient; with the characteristics of embryonic stem cells, they have the potential to develop into all types of tissues and organs. Because XIST functions in early embryonic development, they used induced pluripotent stem cells for XIST silencing. After the gene insertion by homologous recombination (a natural DNA replication and repair during cell division), they initiated the XIST gene expression by turning on a drug controlled switch. They then analyzed the gene profiles including mRNA expression and DNA methylation level and found the cellular activities restored to the normal two-copy chromosome level.

The limits of this technique include very low efficiency of inserting XIST gene into chromosome 21, and use of stem cells for the gene integration. However, with the first working proof, the improvement and alternative approaches will grow, and this strategy may provide a real cure for Down syndrome in the future.


Jiang J, Jing Y, Cost GJ, Chiang JC, Kolpa HJ, Cotton AM, Carone DM, Carone BR, Shivak DA, Guschin DY, Pearl JR, Rebar EJ, Byron M, Gregory PD, Brown CJ, Urnov FD, Hall LL, Lawrence JB.  Translating dosage compensation to trisomy 21. Nature. 2013 Aug 15;500(7462):296-300. doi: 10.1038/nature12394. Epub 2013 Jul 17  (



Thanks for the reviewers’ comments in the Science writing course of Stanford, I corrected some according to reviewers’ advice, though there are still a lot to be improved. I used it in the course to get comments, not recycling, because this website is little visited, and I can not get feedback anyway. But I declare this is my original writing, not plagiarism. Thanks again for your criticize.


Open science for open mind

September 11, 2013

I have been working on neurobiological research for more than 15 years since I graduated from medical school. The first field in neuroscience attracted me is neural stem cells, then the neurodevelopment, and I saw the many breakthroughs happening in the past 15 years in understanding the pathogenesis of neurological diseases and normal cortical development. What Raymond Kurzweil described in his book ‘Singularity is Near”, that an exponential increase in technologies like computers and genetics is somehow true. During my study of Alzheimer’s disease and Down syndrome in the past 15 years, I saw the finish of human genome project, broad applications of high throughput sequencing technology, new frontiers of bioinformatics, epigenetics and induced pluripotent stem (iPS) cells, genome-wide association study (GWAS) to identify susceptible locus for depression and schizophrenia. I used these new technologies myself, including high throughput DNA methylation profiling and iPS cells to discover new pathways in Alzheimer’s disease and Down syndrome, which is unthinkable when PCR is still a new technique when I studied in medical school. I believe all these advances are unachievable without open science approaches.

When I prepared my master thesis 15 years ago, I had to go to libraries to get literature prints using copy machines, and prepared thesis defense slides using developed films. That is the start of my science career though watching copy machine working and staying in darkrooms for film development had not much fun. Nowadays, with one computer connected to internet, I can find almost all the resources and solutions to my questions and technique problems, from the open access to papers, protocols, methods, software, discussions, webinars, and Google becomes the most often used tool instead libraries. With the exponential increase of publications, you can imagine how much time it saves for you to keep you in the frontier of your research field.

The open science approaches not only include the free access to scientific publication like what NIH is doing in PubMed central, but also all other scientific resources that are shared by all the research community. In a recent project on Down syndrome study, we want to study a gene on chromosome 21, which has an extra copy in Down syndrome patients. To examine the gene expression in the Down syndrome brain, we got invaluable frozen brain tissue of specific ages from Brain Bank at National Institute of Child Health and Human Development (NICHD) in Maryland, who had collected thousands of brain samples from different neurological disorders. To manipulate this gene, we got this gene bacterial clone from BACPACResourceCenter” (BPRC) located at the Children’s Hospital Oakland, California. To target this gene in iPS cells, we got transcription activator-like (TAL) effectors nuclease (TALEN) constructs from Addgene contributed by Jung lab in Massachusetts general hospital (MGH), and Down syndrome iPS cells from Harvard Stem cell Institute in Boston. At last, to study the gene in animal models, we got the DS transgenic mice from Jackson Lab in Bar Harbor. With these tools, we can test our hypothesis in 1-2 years; without these resources, it could take years or decades to achieve our goal to find out the gene function in this disorder.

Above is a simple example from my research experience. In addition to this convenience brought by open science approaches, with more people involved, it may facilitate the improvement of quality, education and application of science to benefit the society. Moreover, current challenges are mainly from the increasing data in high throughput screens of genome or epigenome and imaging or electrological recording in normal and diseased people. One single person or organization cannot fulfill these data mining and interpretation work; it has to be a well-coordinated maneuver of many teams and groups. Many institutions and companies have begun to develop integration platforms from these data, such as ExPASy, NEXTBIO, SAGE and the Human Connectome Project, and the open accessibility of the data is essential to achieve the final goal. This open platform for the open mind ensures everyone with curiosity can think about it and contribute their ideas; they can download the data freely to analyze them with their own mathematical models; they can discuss the projects freely with professional or nonprofessional scientists. I believe these efforts will accelerate our understanding of the physiological and pathological mechanisms of human development and diseases, and find more pharmaceutical interferences for curing these diseases.

The open access to scientific resources has changed our view of traditional research. In a time of self-education with free access to information, knowledge and known techniques, it will stimulate more innovative thoughts without restrains. The most important thing is how to use this free information to produce new ideas and techniques. With this knowledge, we could avoid the known knowns and known unknowns to focus on the unknown unknowns, which are the real gold mine of scientific discovery.



January 28, 2011

统计学第一课说的是区别数据种类:“上个月的薪金”这是连续的(continous)还是分散的(discrete)?有学生举手说是分散的,我说我这也有可能。分散的数据一般能用1, 2, 3, 4,。。。的方式给数出来,当然我们可以用1分,2分,。。。10分,11分,。。。的方式来数钱。不过既然大家一般不这么数钱,我更倾向于理解薪金这个东西是连续的。一般来说,分散的数据都是整数,而连续的数据是小数。学生跟我指出,书上说这个是分散的。我说书上说的不一定都是对的,甚至我说的也不一定都对───有的事情,不分对错,而是一个个人趣味(personal style)上的不同。学生们茫然看我,有的也许认为我在给自己打圆场,有的貌似理解了我的意思,有的还有点不解,或者感到我在嘲笑他们。









Strong Opinions

January 27, 2011

Strong Opinions是我最最喜欢的书之一了。。。因为这个原因一直没舍得开始看speak, memory。。 记得纳博科夫用极度刻薄的语言形容托斯陀耶夫斯基,说他是什么“偏执小报记者”之类的。很奇异的两个形容词,可惜太久我居然忘了。—-那次对我好冲击啊,因为我个人一直对老陀崇拜得不行,反倒是对纳博科夫特别欣赏的托尔斯泰不那么感冒。可即便如此,我还是喜欢这个敢说敢想的老头儿。

一直觉得Strong Opinions这本书改变了我很多。──看它的时候在美国已经呆了几年。我一直没想好怎么对待跟别人之间文化上的隔阂。去学人家那套,不愿。完全照自己意思来,不可行。可以这么说吧,从纳博科夫身上,我找到一种坚持自己内心的声音的不卑不亢的行为准则。我是中国人,但不是说我必须把中国说得坏来讨好你,或者必须装成爱中国到为它说好话的程度来凸现自己的人格。应该是本来怎样,还是怎样。




刚才跑去找Strong Opinions,怎么也找不到。楼上楼下跑了三遍,把别的书都给收拾了一遍,只不见这本的踪影。难道被我上次搬家处理掉了?唉,真要命。书这种东西该处理的时候必须处理,可挡不住回来后悔:要翻的时候,它已经没了。





那天吃火鸡的时候突然提起七武士,我尚在搜肠刮肚找怎么说”黑泽明“的英文,旁边一个女孩道,”我也许喝多了,但你们莫不是在说黑泽明吧?“并且她立刻提起黑泽明自己在关于罗生门的一个访谈里说到电影罗生门着重写了一个”旁观者“的视角,有关于日本人自己看日本战后(罗生门拍摄完成于1950年)的意思。我一听大惊失色:这是遇到行家了。当下瞥开关于Magnificent Seven到底好不好的原话题,(因为老板夫人提到Magnificent Seven是个好片,我一句话立刻出口,“不至于吧。”对方脸上有点红红白白,而我就发现自己那个莽撞发表过于鲜明意见的老毛病,又犯了。。。)积极地开始讨论关于罗生门原著小说来自哪里的问题。当提到Dream的时候我不由得说,这个电影不大好哇,昆廷都说了年纪大了不要拍电影,意思就是不想走黑泽明的老路。那个女孩(不好意思难得遇到个聊天的我连人家名字都没记住)说那么八月狂想曲呢,总还不如dream,我顺口道”八月狂想曲那个更是不值一提“,被对方抓住了”not even worth mentioning“的小辫子说我mean,当下我很不好意思再度开始为自己说话太冲而感到郁闷,不由得抱歉半天,被她大度笑之。言多必失,现在说话越来越冲,好像是时候好生反省一下了。


The Zeitgeist: 时代精神

January 12, 2011

今天第一次听说这部电影:The Zeitgeist,我立刻想到去facebook上推荐了一下(显示自己对那些“严肃”的事情有追求,这是我新年新气象要开始建立自己新形象的一个努力)。Google一下就很容易找到此片的主页。而对我来说,最简洁全面的介绍还是来自wiki。作为一个免费在网上发行的电影,youtube或者土豆上当然极容易找到它。于是今晚的娱乐就成了两个人(昏昏欲睡的)看这个电影。。的大半。后来觉得实在无聊,我们聊了一会天,就决定call it a day了。


这个电影最吸引我的地方是它换个角度看问题的角度—-虽然了,就我所知,这个角度在美国中产阶级年轻人里面不算特别的,反倒基本可称得上是主流,至少也是个类主流吧。事实上美国的精英主义早就决定了,这个国家跟人们日常生活里最常看见的那些人很不一样,很不一样。George Carlin在那不是嚷嚷好多年了吗,“这个国家控制在一小撮人手里!一小撮!”

作为一个semi-academic,我对影片表达的相当严肃的学术精神感到钦佩。当然了,任何一种理论说出来,都难免因为成为一个“理论”而给与他人攻击的极大理由,并且多半还与此同时提供了方法。一般来说,只要那句绝对强大的爱丽丝一句“Why Not”就足够了。于是对这些耶稣来自天狼星,财富等于债务,等等的理论,我一边好奇地笑着合不拢嘴,一边准备把这些理论扫到思想里的一个小角落里去,等到有心情的时候(天知道)再给拎出来,晒晒太阳。

作为一个给此片所写的“伪广告”文,我想至少介绍一个证据,给大家看看这位Peter Joseph有多严肃的学术:他给电影写了几百页的“观片手册”—-就象很多人在给讲座的时候发个handout似的—-只是这个手册一下居然有220页。做得相当用心!

也不难在网络上找到关于Zeitgeist的评论文章。最打头的大概是这篇Alan Feuer写在NY Times上的“他们看见了未来,于是就厌恶现在”:从这个标题里,你不难想象Alan对这个Zeitgeist至少不是欢呼着拥抱上去那种态度吧。。。不过呢,那篇文章其实更多是关于一个叫做Venus Project的东东。那是由一个老头Jacqure Fesco所鼓吹的,叫做Zeitgeist Movement或者Venus Project的乌托邦大计,目的是要建立“resource based economy”(资源经济),作为“monetary based economy”(金钱经济)的对立。

我没有花时间细究这一老一小两个人是怎么把自己拿这么个Venus Project给捆绑在了一起。原因有可能有很多,不光可能是出于情趣上的无限相投,更有可能是来自经济共同体的互利—-他们建立的那个Zeitgeist Movement,象任何一个”运动“一样,立刻在美国这个无脑(俗称”no brainer“)人士的超级供应大国搜罗到了高达数十万(一年前的数据)的从众。而在我看来,这个组合无疑是把Joseph原本追求的那种学术严密精神给摧毁了,让他自己从一个对世界充满好奇和愤怒的小青年,转变成了一个贩卖空想和理论的“乌托邦人士”。或许过不多久,他就会象自己影片里所讽刺的那些人那样,拎个话筒到大街上去招呼民众给自己投票了吧。



January 7, 2011

2005年Freakonomics这本书凭空出世,立时众人皆知。到2009年底已经在全世界卖到四百万册之多。我后知后觉地从朋友博客里听说,从公立图书馆还排队等了好一阵子(图书馆的好书一般会被很多人在一个waiting list上等)方才于2009年年中借到手。记得拿到书那天急着想看,拎着它去洗衣房,路上碰到一个陌生的邻居见了那个花花绿绿的封面就抓住我要聊经济学,吓得我夺路而逃。

其实是很浅显易懂的小册子,只是晚上睡觉前翻翻,一个星期就看完了。这本书出名的原因是有一些“耸人听闻”的见地,最挑战美国大众神经的是找到所谓堕胎合法跟犯罪率降低之间的关联。我个人觉得最有意思的部分倒是后半本关于家庭教育(parenting)讨论是所使用的方法,这对于一个完全经济外行的我来说,真是既符合逻辑又很新奇。这本书还有一个很有意思的“卖点”,就是作者(在芝加哥大学任教的Steve)有个黑人朋友跟芝加哥黑帮有过关联,因此提供了不少关于黑帮组织内部的第一手资料。光凭这些内容能在一本经济学类书籍里出现,就能让人看出Steve Levitt这个以做“非常规”经济学话题而出名的人有多么的非常规了。


▪ Chapter 1: Discovering cheating as applied to teachers and sumo wrestlers (See below)
▪ Chapter 2: Information control as applied to the Ku Klux Klan and real-estate agents
▪ Chapter 3: The economics of drug dealing, including the surprisingly low earnings and abject working conditions of crack cocaine dealers
▪ Chapter 4: The controversial role legalized abortion may have played in reducing crime. (Levitt explored this topic in an earlier paper entitled “The Impact of Legalized Abortion on Crime.”)
▪ Chapter 5: The negligible effects of good parenting on education
▪ Chapter 6: The socioeconomic patterns of naming children

第一章,说关于教师为了提高表面上的教学质量(teaching effectiveness)给学生漏题或者直接改分是怎么被抓住的。这章介绍了贯穿全书始终的一个经济学基本概念:有动机(incentive),才有结果(pay off)。





第六章:从给小孩起名看社会经济学。关于此事我后来在freakonimics上看到一篇后续文章,说有个小女孩被起名叫Marijuana Pepsi,因为这个极度可笑的名字渡过异常努力的一生,现在是主持电视节目的成功人士。

顺便介绍一下两个作者。Steven Levitt是哈佛、MIT毕业生在芝加哥大学任教,经济达人。而Stephen Dubner是NY Times资深写手。这种组合的书,一般都很有看头,既能保证知识养分还能兼顾阅读趣味。(这里希望大家推荐类似组合的书。我想收集个书单。)

他们的freakonomics如此成功,以至于很快就出了续集:superfreaknomics。书一出来我立刻在Amazon看到无数坏评,所以一直也没去看。不过这也不大要紧,因为他们在NY Times上的博客涉及到好多偏偏正正的话题,包括有好些就是写进书里的。

从blog里你会发现,这个两人组合已经扩展到一小撮,搜罗了更多经济学人和专栏写手进去。在2010年年中他们还开始了自己的freakonomics podcast,据说在iTunes的2010年终评选里上榜排得第一不过我去iTunes搜索了一下没看见,可能已经算旧闻了吧。我相信他们的人气足以替他们赢得相当一拨读者。不过我个人听的podcast太多,倒不是觉得freakonomics的这一个有多么强大的竞争力。见仁见智吧。



sex and personality – 续续

July 28, 2010