科学美国人60秒 卡夫利奖颁发：理解神经发育和神经退行性变（在线收听）

The Kavli Prize Presents: Understanding Neurodevelopment and Neurodegeneration

卡夫利奖颁发：理解神经发育和神经退行性变

This podcast was produced for The Kavli Prize by Scientific American Custom Media, a division separate from the magazine’s board of editors.

这篇播客是由《科学美国》定制媒体为卡夫利奖制作的，该部门独立于该杂志的编辑委员会。

Megan Hall: Why would a normally developing girl stop walking?  What causes a middle-aged person to lose their sense of balance? Dr. Huda Zoghbi has devoted her career to unraveling these puzzles.

梅根·霍尔：为什么一个正常发育的女孩会停止走路？是什么导致中年人失去平衡感？胡达·佐格比博士的职业生涯致力于解开这些谜团。

She shares The Kavli Prize with Jean-Louis Mandel, Harry Orr, and Christopher Walsh for discovering the genetic pathways behind serious brain disorders.

她与Jean-LouisMandel、HarryOrr和ChristopherWalsh共同获得卡夫利奖，因为他们发现了严重脑部疾病背后的遗传途径。

Scientific American Custom Media, in partnership with The Kavli Prize, spoke with Huda to learn more about her research.

美国科学定制媒体与卡夫利奖合作，与胡达交谈，以了解更多关于她的研究。

The Kavli Prize is a prestigious honor on its own, but the award holds a special place in Dr. Huda Zogbhi’s heart.

卡夫利奖本身就是一项享有盛誉的荣誉，但该奖在胡达·佐格比博士心中占有特殊地位。

Huda Zoghbi: Because it recognizes work that I have so cherished. It is work with my longtime collaborator, Harry Orr, and I so cherish the work as well as our relationship over the years. So to me, this was the sweetest way to recognize that work.

胡达·佐格比：因为它认可了我非常珍惜的工作。这是与我的长期合作伙伴哈里·奥尔（HarryOrr）的合作，我非常珍惜这项工作以及我们多年来的关系。所以对我来说，这是认可这项工作的最甜蜜的方式。

Hall: Huda and Professor Harry Orr both received the Kavli Prize this year, for research that has been intertwined for decades.

霍尔：胡达和哈里·奥尔教授都获得了今年的卡夫利奖，因为他们的研究已经交织了几十年。

Zoghbi: Our collaboration has outlasted most American marriages.

佐比：我们的合作比大多数美国婚姻都要长久。

Hall: It all started when Huda was at the very beginning of her career. She was trying to unravel the genetic cause of a disorder that affected the balance and speech of a large family in Texas. At around 40 years old, affected family members ...

霍尔：这一切都始于胡达职业生涯刚开始的时候。她试图解开一种疾病的遗传原因，这种疾病影响了德克萨斯州一个大家庭的平衡和语言。在40岁左右，受影响的家庭成员

Zoghbi: ... will start feeling a little bit off-balance, if they're making a quick move. And slowly their speech becomes slurred. And that gets worse and worse with time.

佐比：。。。如果他们快速移动，会开始感觉有点失衡。慢慢地，他们的言语变得含糊不清。随着时间的推移，情况越来越糟

Hall: Eventually, the family members lose their ability to walk and talk clearly. They typically die around 20 years later, of causes related to breathing or swallowing problems.

The disorder is known as spino-cerebellar ataxia type 1, or SCA-1.

霍尔：最终，家庭成员失去了清晰行走和说话的能力。他们通常在20年后死于呼吸或吞咽问题。

这种疾病被称为脊髓-小脑共济失调1型，或SCA-1。

Zoghbi: It’s a family with 200 members, and I started immediately driving every few days to Montgomery and collecting samples.

佐比：这是一个有200人的家庭，我开始每隔几天就开车去蒙哥马利采集样本。

Hall: With the samples Huda gathered and the help of her colleagues, she discovered that the gene responsible for SCA-1 was located on chromosome 6. But, she still had a long way to go.

霍尔：在胡达收集的样本和同事的帮助下，她发现负责SCA-1的基因位于6号染色体上。但是，她还有很长的路要走。

Zoghbi: Imagine you map it to the state of Texas, right? And now you want to find where the house is. So we have to really get the map closer and closer and narrow in to get close to it.

Hall: Time passed, and she finally started getting closer to the location of the gene. Let’s say, she’d located the city.

佐比：想象一下你把它映射到德克萨斯州，对吗？现在你想知道房子在哪里。所以我们必须让地图越来越近，越来越窄，才能接近它。

霍尔：随着时间的推移，她终于开始接近基因的位置。比如说，她找到了这个城市。

She also discovered that Professor Harry Orr at the University of Minnesota was studying a similar disorder in the same general area of chromosome 6.

Zoghbi: I read papers by him showing that we are in the same city. And I was like, wow, this guy is impressive. He's done all this work.

她还发现明尼苏达大学的哈里·奥尔教授正在研究6号染色体相同区域的类似疾病。

佐比：我看了他写的文件，表明我们在同一个城市。我想，哇，这家伙真让人印象深刻。他完成了所有这些工作。

Hall: They eventually met and started sharing information. But, over time, it became clear that they were looking at genes in different locations.

Zoghbi: By then Harry had an inkling that his gene is towards one side, let's say the northern side of the city. And I had data to suggest it's at the southern side of the city. So we're far apart.

霍尔：他们最终会面并开始分享信息。但是，随着时间的推移，很明显他们正在研究不同位置的基因。

佐比：到那时，哈利已经知道他的基因是朝着一边的，比如说城市的北边。我有数据表明它在城市的南边。所以我们相距遥远。

Hall: Huda learned a complicated technique to create little “addresses” or markers on chromosome 6 to better locate her gene. And she thought, why not share them with Harry?

Zoghbi: So I called him up. And I said, look, I made those hybrids. If you want to use them, please go ahead and take them and use them. And he was like, great. So, we’re communicating, we’re having a really beautiful, cordial relationship.

霍尔：胡达学会了一种复杂的技术，在6号染色体上创建小“地址”或标记，以便更好地定位她的基因。她想，为什么不和哈利分享呢？

佐比：所以我打电话给他。我说，看，我做了那些混合动力车。如果你想使用它们，请继续使用它们。他说，太好了。所以，我们在交流，我们有一个非常美丽、亲切的关系。

Hall: Huda went on with her research, but she had this nagging thought in the back of her brain.

Zoghbi: I think there's something fishy here.

Hall: How could it be that she and Harry were studying two different diseases if both had similar symptoms, with a genetic cause in the same general region of chromosome 6?

霍尔：胡达继续她的研究，但她脑子里有一个烦人的想法。

佐比：我觉得这里有点可疑。

霍尔：如果她和哈里都有相似的症状，遗传原因在6号染色体的同一个一般区域，那怎么可能她和哈里在研究两种不同的疾病呢？

Zoghbi: I kept pushing and pushing.

Hall: Eventually, Huda found a mistake in the data from the family she was studying—everyone had assumed a group of daughters had inherited SCA-1 from their mother. But it turns out, it was actually the father who passed the disorder to his girls.

佐比：我一直推啊推。

霍尔：最终，胡达在她所研究的家庭数据中发现了一个错误，每个人都认为有一群女儿从母亲那里继承了SCA-1。但事实证明，是父亲把疾病传给了他的女儿们。

Huda quickly worked with a technician to rerun some of her experiments.

Zoghbi: Cataloging everything for all the branches of this family to construct what came from dad, what came from mom. And when we did that, it fell on top of Harry's gene.

Hall: She immediately called Harry.

胡达很快与一名技术人员合作，重新进行了一些实验。

Zoghbi：为这个家族的所有分支编目，以构建什么来自爸爸，什么来自妈妈。当我们这样做的时候，它落在了哈利的基因上。

霍尔：她立刻打电话给哈利。

Zoghbi: I said, Harry, I use this marker, it puts it right on top of your gene. We're working on the same disease.

Hall: Huda was relieved, but Harry was worried.

Zoghbi: Because back then cloning a disease gene was a big deal. Everybody wanted the glory to themselves.

佐比：我说，哈利，我用这个标记，它把它放在你基因的正上方。我们正在研究同一种疾病。

胡达松了口气，但哈利很担心。

佐比：因为当时克隆疾病基因是一件大事。每个人都想把荣耀留给自己。

Hall: Harry asked if Huda wanted him to return the resources she’d shared with him.

Zoghbi: I said, no, no, no, no, you keep them. We work together. Now we really collaborate. Now we're working on the same thing.

15 seconds of silence. And he said, Let's do it.

霍尔：哈里问胡达是否希望他归还她与他共享的资源。

佐比：我说，不，不，不，不，你留着。我们一起工作。现在我们真的合作了。现在我们正在做同样的事情。

15秒的沉默。他说，我们来做吧。

Hall: When Huda and Harry combined their data, they were able to narrow the location of their gene down to about one million base pairs. They slowly examined each gene one at a time.

But then, Huda heard a scientific talk about a disorder that was marked by repeating letters of DNA.

霍尔：当胡达和哈里结合他们的数据时，他们能够将基因的位置缩小到大约一百万个碱基对。他们一次一个地慢慢检查每个基因。

但后来，胡达听到了一个关于一种以重复DNA字母为特征的疾病的科学讨论。

Zoghbi: I said, Harry, we're not going to walk gene by gene. I just heard this awesome talk from Tom Caskey and it's these three bases of DNA that repeat.  Let's just ignore everything else and focus on finding repeats.

佐比：我说，哈利，我们不会一个基因一个基因走。我刚刚听到汤姆·卡斯基（TomCaskey）的精彩演讲，正是这三个DNA碱基在重复。让我们忽略其他一切，专注于寻找重复。

Hall: So, she and Harry divided their genes up,  including a little bit of overlap, and started hunting.

A few weeks later, on the same day...

霍尔：所以，她和哈里把他们的基因分了开来，包括一点重叠，然后开始打猎。

几周后的同一天。。。

Zoghbi: April 8, 1993. He sent me a fax, he discovered the mutation in his family and I sent him a fax, I discovered the mutation in my family.

Hall: Huda and Harry have been working together ever since. Before Huda submits a grant proposal, she always lets Harry know.

佐比：1993年4月8日。他给我发了一份传真，他在家里发现了突变，我给他发了一份传真，我在家里发现了突变。

霍尔：胡达和哈里一直在一起工作。在胡达提交拨款申请之前，她总是让哈利知道。

Zoghbi: Harry, I'm going to do this, this, and this. And he goes perfect. I'm not doing any of that. I will write a letter to assure the reviewers and to tell them how I will help you. And I do the same for him.

佐比：哈利，我要做这个，这个，还有这个。他很完美。我什么都没做。我将写一封信向评审人员保证，并告诉他们我将如何帮助您。我也为他做了同样的事。

Hall: Between them, they’ve discovered that the gene responsible for SCA-1 produces a protein called ATAXIN-1 that causes clumps in the brain and leads to that loss of balance.

They’ve also developed a new type of treatment that improves SCA-1 symptoms in mice.

It’s a rare collaboration in a world that’s highly competitive. What made them do it?

霍尔：在他们之间，他们发现负责SCA-1的基因会产生一种叫做共济失调蛋白-1的蛋白质，这种蛋白质会导致大脑结块并导致平衡的丧失。

他们还开发了一种新型治疗方法，可以改善小鼠的SCA-1症状。

在一个竞争激烈的世界里，这是一次罕见的合作。是什么让他们这么做的？

Zoghbi: I don't think either of us really thought about who's gonna get credit. Honestly. We just wanted to solve this problem. And I think that was the driver.

Hall: Also, they were young.

Zoghbi: I would say most of my good decisions were due to naivety. You know, trust your heart and don’t overthink it, really.

佐比：我认为我们两人都没有真正想过谁会得到信贷。真的我们只是想解决这个问题。我想那就是司机。

霍尔：而且，他们还年轻。

佐比：我想说，我的大多数好决定都是由于天真。你知道，相信你的心，不要想得太多，真的。

Hall: Huda says this collaboration has deepened their knowledge not just of SCA-1, but other neurological disorders, like Alzheimer's and Parkinson's disease.

Zoghbi: In my long-term vision is prevention. And I'm excited about venturing in that area and finding things that we can maybe take a small pill for that’s safe for people who had a family history of disease or had an at-risk genotype.

霍尔：胡达说，这项合作不仅加深了他们对SCA-1的了解，而且加深了他们对其他神经系统疾病的了解，如阿尔茨海默病和帕金森病。

佐比：我的长期愿景是预防。我很高兴能在这一领域冒险，找到一些我们可以服用的小药丸，对有家族病史或有危险基因型的人来说是安全的。

Hall: Her work with Harry is already being used in clinical trials for treating SCA-1 and other disorders.  Her advice for scientists that want to follow in her path? Be patient.

Zoghbi: Everybody looks at me and gets excited because of the big discovery. I want to remind everybody there were years for each of these discoveries. And that's okay.

霍尔：她与哈里的合作已经用于治疗SCA-1和其他疾病的临床试验。她给那些想追随她的科学家们的建议？要有耐心。

佐比：每个人都看着我，因为这个重大发现而感到兴奋。我想提醒大家，这些发现都有好几年的时间。没关系。

Hall: Huda says, in science, it might take a long time for success to come. But when it does, it’s so satisfying. Especially when it’s shared with a good friend.

Dr. Huda Zoghbi is a Professor at Baylor College of Medicine, the Director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and an Investigator with the Howard Hughes Medical Institute.

霍尔：胡达说，在科学领域，成功可能需要很长时间。但当它出现时，它是如此令人满意。尤其是当它与一个好朋友分享时。

Huda Zoghbi博士是贝勒医学院的教授，德克萨斯州儿童医院Jan和Dan Duncan神经研究所所长，霍华德·休斯医学研究所的研究员。

This year, she shared The Kavli Prize in Neuroscience with Harry Orr, Jean-Louis Mandel, and Christopher Walsh.

今年，她与哈里·奥尔、让·路易斯·曼德尔和克里斯托弗·沃尔什共同获得了卡夫利神经科学奖。

The Kavli Prize honors scientists for breakthroughs in astrophysics, nanoscience, and neuroscience—transforming our understanding of the big, the small and the complex. The Kavli Prize is a partnership among the Norwegian Academy of Science and Letters, The Norwegian Ministry of Education and Research, and the US-based Kavli Foundation.

卡夫利奖表彰在天体物理学、纳米科学和神经科学方面取得突破的科学家，这些突破改变了我们对大、小和复杂的理解。卡夫利奖是挪威科学与文学学院、挪威教育与研究部和美国卡夫利基金会之间的合作伙伴。

This work was produced by Scientific American Custom Media and made possible through the support of The Kavli Prize.

该作品由美国科学定制媒体制作，并通过卡夫利奖的支持得以实现。