Episode Transcript
Announcer: 检查最新的研究，告诉你最新的突破, the science and research show is on the Scope.
Interviewer: My guest Dr. 沃尔夫冈·贝尔（Wolfgang Baehr）说，要在科学上取得进步，你必须无所畏惧. 他研究失明的遗传原因，刚刚被ARVO授予职业成就奖, the Association for Research in Vision and Ophthalmology. You've been in the same field for about 30 years..
Dr. Wolfgang Baehr: Almost 40.
Interviewer: Almost 40..
Dr. Wolfgang Baehr: 1976.
Interviewer: Oh, right. 1976, yeah. What has been the most exciting moment of your career?
Dr. Wolfgang Baehr: Well, it's kind of hard, I have published about 200 papers, each one was a major, not each one but most of them were hard work. 在过去的5年里，我发现即使是一篇好论文也很难发表. 这是我两年前在《大发娱乐》上发表的最好的论文之一, we worked five years on this project. And tried eight different [terms], we started with a top major in science, and it was very frustrating. 但最终，大发娱乐把它发表在了《大发娱乐》上. It was a wonderful paper and that was very satisfying. 所以坚持是我的特点. We don't give up.
Interviewer: 你认为你对待科学的态度和你的一些同事有什么不同吗?
Dr. Wolfgang Baehr: Well, I think I do because I'm trained as an organic chemist, 基础科学教育，当我完成博士学位时，我基本上决定放弃化学，学别的东西, and I got into biophysics, fast kinetics, Stopped-flow kinetics and eventually into biochemistry. 然后我来到美国做博士后，从事视网膜研究, so that's really when our research started back in 1976. During that time we started to work on phototransduction, 在视网膜中产生电脉冲的机制是什么, which is transmitted through the optic nerve to the brain, which is initially [meant] for vision.
Interviewer: 在过去的30年里，你所在的领域发生了哪些最显著的变化?
Dr. Wolfgang Baehr: At that time phototranduction was completely unknown, 在那个时候，生物化学是用来识别[听不清00:02:23]来识别g蛋白，比如转导，最终大发娱乐确定了主要成分，然后分子生物学开始了, DNA sequencing became possible in the 1970s, so I was one of the first starting sequencing trials, in [inaudible 02:46] for example. 然后在1990年，第一个与常染色体显性视网膜色素变性相关的突变在视紫红质中被发现. And we decided to take this mutation, make the same mutation in mouse, 老鼠会在体内产生这种分子, which was really not easy in those times.
Interviewer: 我的一个印象是，你不害怕全身心投入.
Dr. Wolfgang Baehr: You have to be fearless. 试着去看看这个新基因的发表和新的突变. 所以大发娱乐很快就能进行基因敲除，因为在老鼠身上相对容易.
Interviewer: 是的，这似乎是让你脱颖而出的东西..
Dr. Wolfgang Baehr: Yes.
Interviewer: 你是在做遗传性视网膜疾病的老鼠模型吗.
Dr. Wolfgang Baehr: 在过去的十年里，大发娱乐可能已经敲除了20种不同的基因, and many of those models were first and unique. Nobody had ever produced any of those mice.
Interviewer: 你能举一个老鼠模型的例子吗？它有什么缺陷，你是如何扭转这些缺陷的?
Dr. Wolfgang Baehr: Well, 最好的小鼠模型是由钙结合蛋白突变引起的显性疾病, which is called guanylate cyclase activating protein, called GCAP for short.
Interviewer: So, basically, 如果GCAP发生突变，就会导致显性疾病，蛋白质就会过度活跃, correct?
Dr. Wolfgang Baehr: 蛋白质过度活跃，但使用cGMP分子，这是破坏光感受器. We depend on cone vision for color vision, acuity, reading newspapers is all dependent on cones, and this disease destroys first, cones. 所以，你基本上变得怕光，因为光的强度是非常有害的. And you start having problems with reading newspapers, begin central vision problems and you wear sunglasses. 所以病人很难慢慢失去视锥视觉和视觉敏锐度然后慢慢失明. 注射了AV病毒的老鼠可以敲碎mRNA...
Interviewer: 当你敲除mRNA时，就会产生更少的蛋白质?
Dr. Wolfgang Baehr: 产生的有害蛋白质更少，视网膜也不会受损.
Interviewer: Right. So, you're taking away the problem in the first place.
Dr. Wolfgang Baehr: 大发娱乐可以减缓损害，并在一年后产生非常积极的影响, 在视敏度和视锥光功能方面有了很大的提高. So in a mouse model it works beautifully, 这个结构的另一个优点是它适用于GCAP的任何突变, there are about 2,000 families worldwide, which have been identified so far, with 100 to 150 patients. 所有这些病人都可以使用相同的[听不清06:01]病毒通过大发娱乐的基因敲除结构可以获得有益的健康体验并显著减缓疾病. The point where we are right now is, is it worthwhile to do clinical trials, there's a very small patient collection...
Interviewer: Right.
Dr. Wolfgang Baehr: In different parts of the country or the world. 你们知道，是否会有公司支持大发娱乐，这是我不知道的问题.
Interviewer: Another aspect, of course, 你的工作是你正在理解光转导的整个过程，并对其工作原理有了新的认识..
Dr. Wolfgang Baehr: Yes, how that works. In the beginning we know all details, and my interest really, is to understand mechanisms leading to disease, and I think we might essentially, each gene is a new area, [of possibilities]
Interviewer: What keeps you fascinated in this work?
Dr. Wolfgang Baehr: Because there's always something new. We've focused, of course, at genes very specific for photoreceptors, 但最终大发娱乐进入了（中心性营养不良），比如影响多个组织. You know, 切除一个基因，其中一些基因会导致胚胎死亡, mice would never be born; or would die early. And, of course, that's much more complicated, you cannot do just retinal research, you have to look into kidneys, for example. 当然，那不是我的研究领域，所以我需要合作者.
Interviewer: Yeah. Yeah.
Dr. Wolfgang Baehr: 但这让它变得更有趣，因为这些疾病非常非常具有破坏性. 但它也扩大了研究范围，让它变得更有趣. Getting into new areas, 我认为这是大发娱乐可以展示的特点.
Announcer: 有趣，内容丰富，而且都是为了更好的健康. This is The Scope, health sciences radio.