Live or die: Katalin Karikó Hungarian Nobel4Covid Vaccine
文章来源: TJKCB2023-10-02 12:30:07

Katalin Karikó on the phone with her sister. She is smiling. Katalin Karikó, PhD, is a renowned biochemist and researcher known for her contributions to mRNA technology and the development of COVID-19 vaccines. She specializes in ribonucleic acid (RNA)-mediated mechanisms, particularly in vitro-transcribed messenger RNA (mRNA) for protein therapies.

More than 15 years ago, Karikó and her colleague Drew Weissman discovered a way to modify mRNA and developed a delivery technique using lipid nanoparticles to ensure that mRNA reaches the appropriate part of the body to trigger an immune response against diseases.

In 2023, Karikó and Weissman were awarded the Nobel Prize in Medicine for their groundbreaking discoveries in mRNA technology. mRNA was discovered in the early 1960s, and research on its delivery into cells began in the 1970s. Karikó’s work has played a significant role in the development of mRNA vaccines, including the COVID-19 vaccines.

 

 

** 

Katalin Karikó is a Hungarian-American biochemist who specializes in ribonucleic acid-mediated mechanisms, particularly in vitro-transcribed messenger RNA for protein replacement therapy. Wikipedia
Born: 1955 (age 68 years), Szolnok, Hungary
Spouse: Béla Francia
Children: Susan Francia
Nationality: American, Hungarian
 

First reactions | Katalin Karikó, Nobel Prize in Physiology or Medicine 2023 | Telephone interview

Nobel Prize 


https://www.youtube.com/watch?v=514nzDeT7WM  
545K subscribers 

“Ten years ago I was kicked out and forced to retire.”

Our new medicine laureate Katalin Karikó told us how much it means to be awarded the Nobel Prize after a scientific career that has been full of challenges. Ten years ago, Karikó was still doing all her experiments by hand but today she has been awarded the medicine prize for her research on mRNA, which led to the development of COVID-19 vaccines.

 


39,441 views Oct 2, 2023 Nobel Prize Conversations
The call from Stockholm woke Katalin Karikó at her home outside Philadelphia. Initially in disbelief, in this interview with Adam Smith, recorded soon after she had learnt of the award of the Nobel Prize for discoveries that accelerated the introduction of vaccines for Covid-19, she recalls her journey from Hungary and some of the setbacks on the path to the mRNA vaccines. "10 years ago I was here in October, because I was kicked out and forced to retire!" Her advice is to not to dwell on the problems: "You have to focus on the things you can change."



 

“Ten years ago I was kicked out and forced to retire.”

Our new medicine laureate Katalin Karikó told us how much it means to be awarded the Nobel Prize after a scientific career that has been full of challenges. Ten years ago, Karikó was still doing all her experiments by hand but today she has been awarded the medicine prize for her research on mRNA, which led to the development of COVID-19 vaccines.


 
 
 
 
 
 
 
 
 
 

这次得诺贝尔奖的 Katalin Karikó

来源: STEMkid 于 2023-10-02 06:09:20 [档案] [旧帖] [给我悄悄话] 本文已被阅读: 3860 次 (291 bytes)

89 年加入Penn,job title 是 Research Assistant Professor,其实就是紫檀看不上的千年博后。开创性工作是在 2005 年在 Weissman 的实验室做的。她的收入在很长一段时间里都在6万以下。没有这些研究人员,就不会有将来的新药

已有8位网友点赞!查看

 

faced struggles and bounced up every time and worked with dedication and integrity in times of your Trials and Tribulations and how you overcame all that and achieved SUCCESS is always appreciated and will be well received. https://edition.cnn.com/2020/12/16/us/katalin-kariko-covid-19-vaccine-scientist-trnd/index.html?   

She was demoted, doubted and rejected. Now, her work is the basis of the Covid-19 vaccine

By Leah Asmelash and AJ Willingham, CNN
Updated 10:59 PM EST, Wed December 16, 2020
Video Ad Feedback
[Jill Biden]
Jill Biden speaks out after President Biden contracts Covid-19
00:45
[brian china economic crisis wang 0715]
'I'm losing my mind': Chinese depositor loses life savings in bank
03:58
[LOS ANGELES, CALIFORNIA - APRIL 21: A man is asked to cough into his arm as part of testing for COVID-19, by a member of the Los Angeles Fire Department wearing personal protective equipment (PPE) in Skid Row, amidst the coronavirus pandemic on April 21, 2020 in Los Angeles, California. 43 people tested positive for COVID-19 at one nearby Skid Row homeless shelter. (Photo by Mario Tama/Getty Images)]
Doctor: Covid-19 BA.5 variant is highly transmissible
02:31
[Fauci]
Dr. Fauci explains why new BA.5 subvariant is concerning
04:58
[Katalin Karikó 12/14/2020 cpt vpx]
Scientist reveals how she celebrated successful vaccine trials
03:57
[gupta screengrab vpx]
Will approaching winter mean new Covid-19 surge?
04:20
[china corona nyc]
Artist wears 27 hazmat suits to protest China's policies
03:08
[hong kong tourism]
See how Hong Kong is trying to revitalize itself after Covid-19
02:23
[Late night Joe Biden]
See late night reactions to President Biden claiming pandemic over
01:45
[Patient using video game treatment long haul covid gupta pkg vpx]
Dr. Gupta: This treatment for 'brain fog' from long-Covid just might surprise you
04:05
Aaron Rodgers tells Joe Rogan why he didn't get vaccinated for Covid
02:16
[BARTLETT, ILLINOIS - MAY 01: Seven-year-old Hamza Haqqani, a 2nd grade student at Al-Huda Academy, uses a computer to participate in an E-learning class with his teacher and classmates while at his home on May 01, 2020 in Bartlett, Illinois. Al-Huda Academy, an Islam based private school that teaches pre-school through the 6th grade students, has had to adopt an E-learning program to finish the school year after all schools in the state were forced to cancel classes in an attempt to curtail the spread of the COVID-19 pandemic. (Photo by Scott Olson/Getty Images)]
How Covid upended children's lives
10:16
[hotez vpx]
'Wasn't too surprising': Doctor reacts to Biden's positive Covid test
02:50
[video thumbnail wuhan market 1]
New studies suggest Covid-19 likely originated from Wuhan wet market
01:39
[Dr. Anthony Fauci]
Dr. Fauci gives update on Biden's Covid-19 infection
05:50
[doctor jonathan reiner]
'This was entirely predictable': Doctor on Biden testing positive for Covid-19
01:22
[Jill Biden]
Jill Biden speaks out after President Biden contracts Covid-19
00:45
[brian china economic crisis wang 0715]
'I'm losing my mind': Chinese depositor loses life savings in bank
03:58
[LOS ANGELES, CALIFORNIA - APRIL 21: A man is asked to cough into his arm as part of testing for COVID-19, by a member of the Los Angeles Fire Department wearing personal protective equipment (PPE) in Skid Row, amidst the coronavirus pandemic on April 21, 2020 in Los Angeles, California. 43 people tested positive for COVID-19 at one nearby Skid Row homeless shelter. (Photo by Mario Tama/Getty Images)]
Doctor: Covid-19 BA.5 variant is highly transmissible
02:31
[Fauci]
Dr. Fauci explains why new BA.5 subvariant is concerning
04:58
[Katalin Karikó 12/14/2020 cpt vpx]
Scientist reveals how she celebrated successful vaccine trials
03:57
[gupta screengrab vpx]
Will approaching winter mean new Covid-19 surge?
04:20
[china corona nyc]
Artist wears 27 hazmat suits to protest China's policies
03:08
[hong kong tourism]
See how Hong Kong is trying to revitalize itself after Covid-19
02:23
CNN — 

Covid-19 vaccines are starting to roll out in several countries, a momentous breakthrough that hopefully signals a light at the end of this dark pandemic. For Katalin Karikó, the moment is particularly special.

Karikó has spent decades of her career researching the therapeutic possibilities of mRNA, a component of DNA that is considered to be one of the main building blocks of life. Through multiple setbacks, job losses, doubt and a transatlantic move, Karikó stood by her conviction: That mRNA could be used for something truly groundbreaking. Now, that work is the basis of the Covid-19 vaccine.

From Hungary to the US

Karikó, 65, began her career in her native Hungary in the 1970s, when mRNA research was new and the possibilities seemed endless. But the call of the American dream (and more researching and funding opportunities) took root.

In 1985, she and her husband and young daughter left Hungary for the US after she got an invitation from Temple University in Philadelphia. They sold their car, Karikó told The Guardian, and stuffed the money – an equivalent of about $1,200 – in their daughter’s teddy bear for safekeeping.

这个诺奖得主曾在肉铺卖香肠,父亲想让她也当屠fu 卡里科在匈牙利一个只有1万人的小镇长大,小时候家里没有自来水,也没有电视或冰箱。她的父亲是屠夫,母亲是会计员。家里开了一家肉店,卡里科小时候会去店里帮忙做香肠。
 
卡里科一开始在匈牙利做研究,但缺乏研究资金,于是决定前往美国做博士后。



1985 年 9 月,卡塔琳·卡里科 (Katalin Karikó) 与丈夫贝拉·弗兰西亚 (Béla Francia) 以及 2.5 岁的女儿苏珊 (Susan) 抵达美国一个月后,乘坐他们的第一辆车。|sciencenews.dk

1985年,卡里科从匈牙利前往美国。由于匈牙利政府只允许她一家带100美元出境,她和丈夫将900英镑(约合今天8943元人民币)缝进了2岁女儿的泰迪熊里。

上图抱着泰迪熊(全家最重要财产)的女儿苏珊·弗朗西亚(Susan Francia),后来成为赛艇选手。2008年,苏珊在中国北京奥运会上获得女子八人制赛艇项目金牌,并于4年后在此项目中再次夺冠。
 
卡里科打过一个比方,做科学和她女儿划赛艇有相似之处,赛艇运动员是背对着自己前进的方向的,“她们看不到终点线,看不到距离终点线还有多远,她们只是隐约感觉得到。科学有时也是这样。
背对着终点的弗朗西亚|bioenergylifescience
 
 
也是在2013年,宾夕法尼亚大学告诉卡里科“她不具备教授的素质”,决定不和卡里科续约。

卡里科告诉宾夕法尼亚大学自己要去BioNTech,被嘲笑说,“BioNTech连个官网都没有。”

卡里科觉得,比起学术界,生物产业界有很多优点,在产业界你做的是功效强、能治愈人们的产品,这比一篇又一篇没人读的论文要好得多。
 

美国mRNA疫苗诺奖得主没有那么惨

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
打印(被阅读 4021次)

中国人喜欢看热闹,他们不是看出修饰核苷酸后能够使mRNA更容易存活这一创造,而是为了流量专门去夸大诺贝尔奖得主的职业遭遇。当然Katalin Kariko也是一个great story teller,她的这点很值得我们学习。

我见到的最雷人的标题是“这位屠夫的女儿如何获得诺奖”,所有我们桌上的肉类是否都是屠夫们的产物?

现在通过访谈透露出更多的Katalin Kariko的职业人生的细节,在UPenn发海报庆祝的时候,看看当年那些Penn的系主任们是如何对待她的。

她仍然难忘宾大在10年前将她踢出大学,在接受诺贝尔奖记者Adam Smith采访时,使用的是她被“kicked out”。

这是她在更早时接受采访时说的:“2013年,卡里科与宾夕法尼亚大学又发生一次不愉快,校方拒绝恢复她1995年降薪的教师职位,又在知识产权许可上与她产生分歧(宾大将知识产权卖给了另一家公司)。最终,卡里科选择辞职,加入BioNTech并担任高级副总裁。校方对卡里科极尽刻薄,称BioNTech是一家连网站都不存在、名不见经传的小公司,暗示卡里科的选择毫无价值”。

我们也不能责怪Penn, 如果在任何美国很多一流医学院,她也会面对同样的命运,美国学术之路就是这么残酷。这里关键是钱,谁都不愿意养活你,只有你有价值才能在美国学术界生存。你必须抬起头,在优秀人群中相信自己。


普林斯顿可以善待《美丽心灵》电影里的诺奖得主John Nash, 让他患精神病还在校园。但是他是单枪匹马的数学家,学校的付出有限,如果Nash要求普大每年百万运转实验室看看?

我们学校的著名教授Charlie Parker够优秀吧,几乎在前列腺素领域获得诺贝尔奖,但是当他失去基金后照样关门。我是看着他过来的,最后一个印度技术员走后,他自己做实验。然后实验室关门后,自己在以前学生的实验室找空位做实验,人家曾经是科主任一级的人。

Katalin是典型的美国移民科学家的奋斗史,与走路顺利的耶鲁毕业生相比,充满坎坷。但是她仍然是相当幸运的,在美国常春藤至少当过教授,后来又做资深副总裁。

想想更多的优秀美国移民科学家,他们的大部分都不可能做教授,一辈子都没有她这样的机会。

让我们再看这段转言:“距离最早卡里科研究mRNA过去整整32年(至2020年)。32年中,卡里科个人年收入从来都没有超过6万美金,在冷门到几乎无人问津的领域内坚持耕耘,无数次被拒绝、甚至被降职”

这个传言几乎不可能是真实的,Penn的pay scale(教授工资定级)不会是这样的。况且她在2013年就被迫从Penn辞职了,去德国成为BioNTech 的SVP,怎么至2020年的32年间没超过6万?

我可以这样猜测一下,Katalin现在的资产总值应该超过了千万美金,包括退休金,房产,工资和股票分红或奖金。这对于只将800元缝入女儿玩熊的东欧移民,已经是美梦成真了,对任何人都是。

这是她们的Immunity论文的发表过程。Nature拒稿诺奖工作只需24小时,我们也经历过这样的拒稿,隔壁教授曾经解释说,英国人不懂美国英语:

“卡里科:这个进展,如你所说,我们首先发送到《自然》杂志,在24小时内,他们就拒稿,认为我此前在这方面没基础(incremental contribution,逐步累积的贡献)。我是大学才开始学英语的,所以还要查“incremental”这个词的意思!不管怎样,我们随后把它送到了Immunity,他们接受了它。德鲁和我几乎做了所有的工作。即使在58岁的时候,我也没有太多的人力或资金援助来进行实验,所以我只能自己动手做。2008年,我们花了一段时间在Molecular Therapy《分子治疗》上发表了后续论文”

有读者称她英语没有问题,但是离真正英语好还是有距离的。

Katalin称她在58岁还在做实验,这也没什么,根本不惨。科学家本身就是应该做实验的,就像医生应该看病人,咨询老师必须带学生一样。在我看来,做实验的乐趣超过了坐办公室。

世界引用率之最的Oliver Lowry在70-80岁都拿着冰盒做实验,他曾经这样说,有人付工资让自己做喜欢的东西,这是世界上最幸福的职业。

这里讲点免疫学的基础知识,人体核酸含有大量被修佈的核苷酸,而细菌和病毒里则少,所以人体免疫系统专门攻击外来物,对自己身体的东西则耐受。

这是免疫系统中经常会遇到的识别“自己”和“异己”的问题,弄不好就会得自身免疫性疾病,让你痛苦不堪。诺贝尔得主Katalin Kariko的创造正是让免疫系统也耐受外源mRNA, 从而为人类造福。

这是十分聪明和了不起的成就,通过生化学家与免疫学家通力合作才取得的。Drew Weissman是福奇训练出来的免疫学家,他在接受诺贝尔采访时说,他们是在实验台一起做实验的。

可以延伸说一下,Katalin Kariko和Drew Weissman的合作关系。他们的鲜明反差已经超过了女士和男士,前者多语,后者不太健谈。前者是高大金发的北欧态式的奥运金牌母亲,后者是细心的犹太人。

后者向前者发工资,但是前者将技术带入后改变了实验室,这里Weissman的胸怀了得,这是发生在Penn的所谓Weissman Lab的故事。

可以谈点别的,那些我怎么告诉华大优秀的MD/PhD学生的话。我说你未来是否能成功,关键看你如何为人,因为你科学上已经很聪明。

你未来建实验室,或者拿到NIH Grant, 你一定要摆正心态。千万不要以为是你在为博士生或博士后发工资,应该认为美国纳税人相信你,委托你,使用这些工资去做精采的科学。


冷泉港亚洲CEO季茂业的照片,经允许转载。上周他们举行了庆祝重组DNA五十周年的纪念活动,著名科学家云集。Eric Lander和Francis Collins还有老的时候,张锋也受邀赴会。首先讲的还是华大医学院校友Dan Nathans发现限制性内切酶的故事,他长期在Johns Hopkins当教授,华大与Hopkins相连。


Katalin Kariko在诺奖电话中谈到此会议,说刚从Cold Spring Harbor 回来。季老师说:“大家都是移民,共鸣多”。Katalin在冷泉港也受邀讲mRNA治疗,我可是见识过匈牙利的优秀化学家,这次在英国开会,匈牙利同行教我好多。

从Katalin的幻灯看,她们的切入点是自然的tRNA,她们发现tRNA因为含有修佈的核苷酸而不被机体的免疫系统排斥。我想她们认识到这点后,以后就可以设计转录试验,加入从公司里买的修佈好了的核苷酸,这样治疗用mRNA就成行了,可以去读他们Immunity论文。现在马后炮说来都很顺,只是很多时候摆在眼前的东西,我们都看不见。

 
 
BMC 发表评论于 
RNA contains four bases, abbreviated A, U, G, and C, corresponding to A, T, G, and C in DNA, the letters of the genetic code. Karikó and Weissman knew that bases in RNA from mammalian cells are frequently chemically modified, while in vitro transcribed mRNA is not. They wondered if the absence of altered bases in the in vitro transcribed RNA could explain the unwanted inflammatory reaction. To investigate this, they produced different variants of mRNA, each with unique chemical alterations in their bases, which they delivered to dendritic cells. The results were striking: The inflammatory response was almost abolished when base modifications were included in the mRNA. This was a paradigm change in our understanding of how cells recognize and respond to different forms of mRNA. Karikó and Weissman immediately understood that their discovery had profound significance for using mRNA as therapy. These seminal results were published in 2005, fifteen years before the COVID-19 pandemic.
BMC 发表评论于 
@irisin2021: 请仔細阅读诺奖委員會的官方声明,它明确指出, Kariko发表在2005Immunity的文章(甲基化RNA以逃避免疫攻击)是她获今年诺奖的原因。
irisin2021 发表评论于 
假尿嘧啶不是尿嘧啶的修饰物,而是同其他4种碱基一样,独立存在的第5种碱基。
irisin2021 发表评论于 
微博中有一个博文“我的师姐-mRNA技术奠基人卡特琳-卡里科博士”。比较准确介绍了Dr.Kariko。目前网上许多文章并不准确。她对科学的贡献不是mRNA,而是“假尿嘧啶和假尿嘧啶在mRNA中的生物作用“,她提出,DNA有四种碱基,而mRNA有五种碱基,缺一不可。covid疫苗只是她这个理论的应用而已
BMC 发表评论于 
Typo, 应该是TLR 而不是TRL
BMC 发表评论于 
今年的诺贝尔医学奖授予了对的人和对的事,但也有遗憾,漏掉了间接促成RNA疫苗的人,我认为这人也应获今年诺奖。Kariko 获奖的原因是她在2005年发表在Immunity 的文章,提出用甲基化RNA 的方法免除RNA 受到TRL3, TRL7 和TRL8的免疫攻击而得以在体內转译蛋白质,但这个发现不是Kariko 的原创,她是受到甲基化DNA的CpG片段可以使DNA免受TRL9攻击这一发现的启发才想到甲基化RNA. 第一个做甲基化DNA的人才是最重要的的RNA疫苗的功臣。这与MIT的张鋒与伯克莱加大的Jennifer Doudna争2020诺贝尔医学奖有点相似。Doudna 是基因编辑CRISPR的发明者,但只是在原核细胞上。后来张锋把CRISPR应用到真核生物细胞上,这就极大地扩大了基因编辑技术的应用。Doudna的技术只是一种实验室技术,而张锋的技术有很大的商业价值。二人因此而为专利权和诺奖争得不可开交。最后Doudna得2020诺奖,张锋却贏了专利官司。我觉得这是最合理的,因为Doudna是发现者,而张锋是应用者,而诺奖讲究原创性,所以给了Doudna. 如果你明白了为什么Doudna而不是张锋得2020诺奖,你可能也会觉得今年的诺奖不包括DNA甲基化逃脱免疫攻击的发现者确实不公平。
宇都宫 发表评论于 
谢谢好文分享!想起了“耐得住寂寞”的母亲,她把一辈子奉献给了科研,最后因病早逝。
雅美之途 发表评论于 
回复 '零不是数' 的评论 : 谢谢,必须相信我,放朋友圈时改过一次。
零不是数 发表评论于 
精彩,不是“精采”。