章节 1：百年巨头与完美的一品脱 (The 150-Year Giant & The Art of the Pour)

📝 本节摘要：

访谈在一种轻松的氛围中拉开序幕。Eli Lilly（礼来）的第11任CEO Dave Ricks以娴熟的手法为自己倒了一杯吉尼斯黑啤，这一举动被主持人风趣地称为“实力的炫耀（Major flex）”。开场旁白简要勾勒了礼来公司的行业地位：作为一家拥有150年历史、市值7000亿美元的制药巨头，它不仅是全球最有价值的制药公司，正凭借GLP-1药物引领市场，并通过LillyDirect直销模式颠覆传统的医药分销体系。

[原文] [Dave Ricks]: I'm the 11th CEO of the company. That's one less than popes in that period of time.

[译文] [Dave Ricks]: 我是这家公司的第11任CEO。在同一时期内，这个数量比教皇的人数还少一个。

[原文] [Host]: Where did you learn to pour?

[译文] [Host]: 你是在哪里学会倒酒的？

[原文] [Dave Ricks]: I actually learned in Ireland.

[译文] [Dave Ricks]: 我其实是在爱尔兰学的。

[原文] [Host]: Okay, do you want me to leave it down? You're the expert here.

[译文] [Host]: 好吧，你要我把它（杯子）放下吗？你才是这方面的专家。

[原文] [Dave Ricks]: Okay, oscillate this way.

[译文] [Dave Ricks]: 好的，让它这样回旋流动。

[原文] [Host]: That's an excellent pint.

[译文] [Host]: 这是一杯极好的啤酒。

[原文] [Dave Ricks]: Yeah.

[译文] [Dave Ricks]: 是的。

[原文] [Narrator]: Dave Ricks is CEO of Eli Lilly, which is now a $700 billion company and the world's most valuable pharma company. Eli Lilly is 150 years old. They grew up as the first company to mass produce insulin in the 20th century. But today most of the company's business is in the new GLP-1 diabetes and weight loss drugs where they've become the market leader. Simultaneously, Eli Lilly is upending the traditional model by selling directly to their consumers over the internet with LillyDirect rather than through the traditional middleman.

[译文] [旁白]: Dave Ricks是Eli Lilly（礼来公司）的CEO，该公司目前市值7000亿美元，是全球最有价值的制药公司。礼来公司已有150年的历史。他们在20世纪作为首家大规模生产胰岛素的公司而成长起来。但如今，该公司的主要业务集中在新型GLP-1糖尿病及减肥药物上，并在该领域成为了市场领导者。与此同时，礼来正在颠覆传统模式，通过LillyDirect在互联网上直接向消费者销售产品，而不是通过传统的中间商。

[原文] [Host]: All right, cheers.

[译文] [Host]: 好的，干杯。

[原文] [Dave Ricks]: Cheers.

[译文] [Dave Ricks]: 干杯。

[原文] [Host]: Cheers. Thanks for coming.

[译文] [Host]: 干杯。感谢你的到来。

[原文] [Dave Ricks]: Good to be here.

[译文] [Dave Ricks]: 很高兴来到这里。

[原文] [Host]: I'm very impressed that you came and you just poured your own pint.

[译文] [Host]: 我印象非常深刻，你来了并且亲自倒了自己的这杯酒。

[原文] [Dave Ricks]: Poured my own pint, yeah.

[译文] [Dave Ricks]: 倒了我自己的酒，是的。

[原文] [Host]: Major flex.

[译文] [Host]: 绝对是实力炫耀（Major flex）。

[原文] [Dave Ricks]: Have glass, will pour.

[译文] [Dave Ricks]: 只要有杯子，我就能倒。

[原文] [Host]: Exactly. Well, actually a good place to start.

[译文] [Host]: 没错。好吧，这其实是一个很好的开始。

(注：原文开头提及的“R&D投入对比德国”部分为视频预告片段，将在后续关于研发经济学的章节中完整呈现)

章节 2：AI超算与药物研发的“外星”化学 (AI Supercomputers & The "Alien" Chemistry)

📝 本节摘要：

对话迅速切入前沿科技话题。主持人询问了礼来与NVIDIA的最新合作——构建一台专注于生物学的超级计算机。Dave Ricks详细解释了AI在“生成式化学”中的应用，即利用算法设计出人类化学家难以构想的“正交”分子结构（以口服GLP-1为例）。然而，面对行业内关于AI的过度乐观情绪（如化学博主Derek Lowe的批评），Ricks表现得十分理性：他承认AI目前在“靶点选择”和“毒性预测”上尚未发挥决定性作用，并指出核心瓶颈在于人类对基础生物学的认知尚浅（仅掌握了约10-15%），缺乏足够的高质量训练数据。

[原文] [Host]: Tell us about your NVIDIA announcement that you just had.

[译文] [Host]: 给我们讲讲你们刚刚发布的关于NVIDIA（英伟达）的公告吧。

[原文] [Dave Ricks]: Yeah, so today at the, what's it called, GTC conference they have, they unveiled that we're well underway, actually it should be done by the end of the year, but building a supercomputer on-prem for us really just to run proprietary drug discovery models.

[译文] [Dave Ricks]: 是的，就在今天的——叫什么来着——GTC大会上，他们宣布我们要——实际上项目已经在顺利进行中，应该会在今年年底前完成——我们要建立一台本地部署（on-prem）的超级计算机，专门用来运行我们专有的药物发现模型。

[原文] [Dave Ricks]: We think it's the biggest biologically-focused supercomputer there is. And certainly the biggest pharma's done with B300s, the latest chip set. And, yeah, we're only constrained by power, like everyone else.

[译文] [Dave Ricks]: 我们认为这是目前存在的最大的生物学专用超级计算机。当然也是制药公司中使用B300（最新芯片组）所构建的最大规模的超算。而且，是的，和大家一样，我们唯一的限制就是电力。

[原文] [Dave Ricks]: But, yeah, we've built a bunch of tools, we'll run them on that, and scientists use it to sort of co-invent, co-develop. Focus mostly on chemistry to begin with, but we'll expand from there.

[译文] [Dave Ricks]: 不过，是的，我们已经构建了一堆工具，我们将在这台机器上运行它们，科学家们会利用它来进行某种“共同发明”或“共同开发”。起初主要集中在化学领域，但我们会从那里扩展开来。

[原文] [Host]: And so is the idea here you have some target, you've had some challenges actually drugging it, and so you give it to one of these new chemistry models and you ask it whether it can come up with something totally orthogonal beyond what—

[译文] [Host]: 所以这里的思路是，你有一个靶点，但在实际成药（drugging it）方面遇到了一些挑战，于是你把它交给这些新的化学模型之一，问它能否想出一些完全正交的（orthogonal）、超乎常规的方案……

[原文] [Host]: Correct, yeah. A human might have tried.

[译文] [Dave Ricks]: 正确，是的。超乎人类可能尝试过的范畴。

[原文] [Host]: So take a really good popular example is like GLP-1. So that's a hormone peptide that we all excrete. It engages targets that are what we call G protein-coupled receptors. So they're hard to drug targets on the outside of cells.

[译文] [Dave Ricks]: 举一个非常恰当且流行的例子，比如GLP-1。这是一种我们要分泌的激素肽。它结合的靶点是我们所说的“G蛋白偶联受体”（GPCRs）。这些位于细胞外部的靶点很难针对性地开发药物（hard to drug）。

[原文] [Dave Ricks]: And to try to mimic a big huge protein with a very small chemical is a complicated undertaking. And by the way, do only that and not other things that are untoward.

[译文] [Dave Ricks]: 而且，试图用一个非常小的化学分子来模仿一个巨大的蛋白质，是一项复杂的任务。顺便说一句，还得只做这件事（起效），而不能引发其他不好的副作用。

[原文] [Dave Ricks]: And so this is sort of a frontier of drug discovery that's been tough and very empirical. That's a hot area for this kind of technology because these strange arrangements of atoms don't look like other drugs that have come before, but they do follow the principles of organic chemistry and seem to engage these targets effectively.

[译文] [Dave Ricks]: 所以这算是药物发现的一个前沿领域，一直以来都很艰难且非常依赖经验。这正是此类技术的热门应用领域，因为这些奇异的原子排列看起来并不像以前出现的任何药物，但它们确实遵循有机化学的原理，并且似乎能有效地结合这些靶点。

[原文] [Dave Ricks]: I don't know of one that's come through the machine-driven discovery process, which is really machine plus human, that's made it to the clinic yet, but they're coming. And I think that's exciting because those have been structures that are, they don't exist in nature, and yet the machines are alien and they can predict these interactions.

[译文] [Dave Ricks]: 我目前还不知道有哪个完全通过机器驱动的发现过程（实际上是机器加人）做出来的药物进入了临床阶段，但它们快来了。我认为这令人兴奋，因为那些结构在自然界中并不存在，然而机器是“异类（alien）”的，它们能预测这些相互作用。

[原文] [Host]: I'm always struck by Derek Lowe's arguments where he's always sounding this note of caution I guess about the optimism and maybe what he might view as boosterism around AI and biomedicine where, as I see at least, his two claims are, one, it's really hard to select the targets and AI doesn't help you that much there.

[译文] [Host]: 我总是对Derek Lowe（知名药物化学博主）的论点印象深刻，他对AI和生物医学领域的乐观情绪——或者他可能视为“吹捧（boosterism）”的现象——总是发出警告。据我所见，他的两个主要观点是：第一，选择靶点真的很难，而AI在这方面并没有太大帮助。

[原文] [Dave Ricks]: No.

[译文] [Dave Ricks]: 没错（没太大帮助）。

[原文] [Host]: And then so much fails at, like, human toxicity. And again, at least so far, AI has not been all that helpful at that step.

[译文] [Host]: 第二，很多药物失败在人体毒性上。同样地，至少到目前为止，AI在这个步骤上也没有那么大的帮助。

[原文] [Dave Ricks]: Yes.

[译文] [Dave Ricks]: 是的。

[原文] [Host]: Do you agree with him or is he overrating, you know, these particular challenges and maybe underrating the challenges that AI does help solve thoughts on that argument?

[译文] [Host]: 你同意他的观点吗？还是说他高估了这些特定的挑战，或者可能低估了AI确实能解决的那些挑战？你怎么看这个争论？

[原文] [Dave Ricks]: Probably we need to create the equivalent of what got created with human language, which is a more complete repository of biological knowledge to train against before the machines get a lot better.

[译文] [Dave Ricks]: 我们可能需要像人类语言领域那样，建立一个更完整的生物学知识库来进行训练，这样机器才能大幅进步。

[原文] [Dave Ricks]: And today, I don't know, I would estimate we might know 10%-15% of human biology. So the machine's not going to be good at all until we get way above 50%.

[译文] [Dave Ricks]: 而今天，我不确定，我估计我们可能只了解人类生物学的10%到15%。所以，直到我们将这一认知提升到远超50%之前，机器的表现都不会太好。

[原文] [Dave Ricks]: That probably requires, you know, robotic 24/7 experiments just to create training data sets and, you know, sort of this kind of big lift effort. The kind of thing actually NIH should be doing right now, I would think.

[译文] [Dave Ricks]: 这可能需要机器人进行全天候（24/7）的实验，仅仅是为了创建训练数据集，也就是那种需要大力气投入的工作。我认为这其实是NIH（美国国立卫生研究院）现在应该做的事情。

[原文] [Dave Ricks]: But that effort's not ongoing, at least in our country. But I think if that gets going, I think we'll know more and the machines get better at the harder big problems, system prediction.

[译文] [Dave Ricks]: 但这种努力目前并没有在进行，至少在我们国家没有。但我认为如果这能启动起来，我们会了解更多，机器也会在更难的大问题——即系统预测——上变得更好。

章节 3：30亿美元的豪赌与科学决策 (The $3 Billion Bet & Scientific Decision Making)

📝 本节摘要：

本节深入探讨了Dave Ricks作为非科学背景出身的CEO，如何掌舵一家顶尖制药公司。他分享了自己“保持好奇心”的学习方法，并透露自己在会议中会实时使用AI（如Claude或xAI）来辅助理解科学问题。在决策风格上，Ricks形容礼来采用的是“魔球（Moneyball）”式的严谨数据分析与领导层“品味”的结合。对话随后转向令人咋舌的研发经济学：礼来每年的R&D投入高达140亿美元，超过了德国的国家级投入；而开发一款新药的平均成本高达35-40亿美元，其中60%的资金都燃烧在风险最高的“最后阶段”——三期临床试验上。

[原文] [Host]: Patrick and I did not, well, just didn't finish any college. So not only don't have a, you know, formal training in computer science, but don't have formal training in anything. You did not come up through the science side of Eli Lilly, but you seem extremely comfortable with the science. What has been your method for ingesting all this stuff, like, and especially as you're essentially making science decisions at the end of the day with the top-level capital allocation decisions? Just how do you learn?

[译文] [Host]: Patrick和我并没有——嗯，就是没读完大学。所以我们要么没有计算机科学的正式训练，甚至没有任何专业的正式训练。你并非出身于Eli Lilly的科研线，但你似乎对科学内容极度游刃有余。你吸收这些知识的方法是什么？特别是考虑到你归根结底是在做科学决策——那些顶层的资本配置决策。你是如何学习的？

[原文] [Dave Ricks]: No, that's right. I think we probably make three or four important decisions a year and they're all science. I don't know. Stay curious.

[译文] [Dave Ricks]: 不，你说得对。我想我们一年大概要做三四个重要决策，而它们全都是关于科学的。我不知道（有什么秘诀），保持好奇心吧。

[原文] [Host]: Mm-hm. Read. Read what?

[译文] [Host]: 嗯哼。阅读。读什么？

[原文] [Dave Ricks]: I read a lot of medical journals. I go to conferences where data is presented. I spend time with our scientists. Stay curious.

[译文] [Dave Ricks]: 我读大量的医学期刊。我去参加那些展示数据的学术会议。我花时间和我们的科学家在一起。保持好奇心。

[原文] [Dave Ricks]: Now I have like at least one or two AIs running every minute of every meeting I'm in and I just am asking it science questions.

[译文] [Dave Ricks]: 现在，我在参加每一个会议的每一分钟里，至少都运行着一两个AI，我一直在问它科学问题。

[原文] [Host]: So you found for your learning ChatGPT or whatever your—

[译文] [Host]: 所以你发现为了学习，ChatGPT或者是你们用的什么——

[原文] [Dave Ricks]: I don't use that one for science. ChatGPT's too verbal.

[译文] [Dave Ricks]: 我不用那个（ChatGPT）做科学用途。ChatGPT太啰嗦了（too verbal）。

[原文] [Host]: Wait, so which one do you use for science?

[译文] [Host]: 等等，那你用哪个来做科学研究？

[原文] [Dave Ricks]: I tend to use either Claude or the xAI one. I find it more terse and the references actually check out more often. Sometimes the AIs produce references and they're actually not the thing that it said and that takes too much work to go cross reference.

[译文] [Dave Ricks]: 我倾向于使用Claude或者xAI的那个。我发现它们更简洁（terse），而且引用的参考文献通常更准确。有时候AI生成的参考文献实际上并不是它所说的那样，去交叉核对太费功夫了。

[原文] [Host]: So for an autodidact, presumably the emergence of LLMs has been transformative for you.

[译文] [Host]: 所以对于一个自学者来说，大语言模型（LLMs）的出现想必对你来说是变革性的。

[原文] [Dave Ricks]: Yeah, well, I think for learning, that's a whole nother topic we could talk about, but you have to sort of question the, like, pedagogical kind of method period. If you can just learn continuously—

[译文] [Dave Ricks]: 是的，嗯，我认为关于学习，那是我们可以探讨的另一个大话题，但你必须某种程度上质疑那种——你知道的——教学法式的模式。如果你能持续不断地学习——

[原文] [Host]: It's mastery learning for everyone.

[译文] [Host]: 这就是针对每个人的“精通式学习（mastery learning）”。

[原文] [Dave Ricks]: Yeah, yeah, exactly. So you take advantage of that. But, you know, early in my career, I started in our business development M&A group and I spent my whole time with scientists looking at little companies and projects in other companies and trying to understand what they were worth. Well, then you have to understand what they do and, you know, I found that part of the industry, I didn't expect that when I came to Lilly. I came to the company accidentally by the way. But when I found that, I was like, "Wow." I loved it. This is so interesting.

[译文] [Dave Ricks]: 是的，没错。所以你要利用这一点。不过，在我职业生涯早期，我是从业务发展并购部门（M&A）开始的，我整天和科学家们在一起，考察小公司和其他公司的项目，试图弄清楚它们值多少钱。既然如此，你就必须理解它们是做什么的。我发现了这个行业的这一面——我来礼来的时候完全没料到这个。顺便说一句，我加入这家公司纯属偶然。但当我发现这一点时，我想，“哇。”我爱上了它。这太有趣了。

[原文] [Dave Ricks]: And then I had a moment where one of the projects I worked on became a medicine in the US and my mother was diagnosed with a condition and she got put on it. And so then that's the magic. It's like, okay, you can work on things that change people, but the people you care about, that's—

[译文] [Dave Ricks]: 然后我有过这样一个时刻，我参与的一个项目在美国成了一款药物，而我的母亲被诊断出某种疾病，她用上了这款药。那就是魔法时刻。这就好比，好吧，你可以从事改变人们生活的工作，但这其中有你在乎的人，那是——

[原文] [Host]: You saw the full end-to-end impact.

[译文] [Host]: 你看到了完整的端到端的影响。

[原文] [Dave Ricks]: That's what purpose is. From lab, exactly. So special.

[译文] [Dave Ricks]: 这就是使命感（purpose）。从实验室（到患者），正是如此。非常特别。

[原文] [Host]: Your four big decisions a year that are kind of grounded in science, how quantitative versus qualitative do these end up being? Are you Rick Rubin, where it's all taste based and you just like the feel of this direction? Or are you Billy Beane where it's a "Moneyball" type, you know, the ROI pencils and—

[译文] [Host]: 你每年那四个基于科学的重大决策，最终是定量的多还是定性的多？你是Rick Rubin（著名音乐制作人）那种风格，完全基于品味，只是喜欢这个方向的感觉？还是你是Billy Beane（《点球成金》原型）那种“魔球（Moneyball）”类型，看重投资回报率（ROI）的计算和——

[原文] [Dave Ricks]: I think the system does a lot of the Billy Beane. I think that's a change at Lilly that's made us more successful. I think we've actually put together a decision process that's quite a bit more rigorous than it used to be and that leads to fewer bad decisions. That's good. So that's sort of like the bumpers on the bowling alley that you put up.

[译文] [Dave Ricks]: 我认为我们的系统做了很多“魔球”式的工作。这是礼来的一个变化，让我们变得更成功。我认为我们实际上构建了一个比过去严谨得多的决策流程，这减少了糟糕的决策。这很好。这就像是你竖起的保龄球道护栏。

[原文] [Dave Ricks]: But then within that, whether it's a strike or a single pin, that's a little bit of the judgment and taste. And there, though, you know, wisdom of crowds, I think we have a great leadership team and we all come with equal voice and sort of debate. We actually have a rule to like never decide in one meeting. So you're asking about the day, but we, like, come back to it, think about what others said and kind of push it again.

[译文] [Dave Ricks]: 但在那之后，是打出全中（strike）还是只击倒一个瓶，这就要靠一点判断力和品味了。在这方面，你知道，“群体的智慧”，我想我们有一个很棒的领导团队，大家都有平等的话语权并进行某种辩论。我们实际上有个规矩，就是绝不在一次会议上做决定。所以你问的是这一天，但我们会回过头来，思考别人说了什么，然后再推进一次。

[原文] [Host]: And are you deciding?

[译文] [Host]: 是由你来拍板吗？

[原文] [Dave Ricks]: Ultimately yes. Nothing happens unless I say go, and if I don't like it, then it definitely doesn't go. But people will often persuade me and I definitely change my mind.

[译文] [Dave Ricks]: 最终是的。除非我说行，否则什么都不会发生；如果我不喜欢，那肯定就推行不下去。但人们经常能说服我，我也确实会改变主意。

[原文] [Host]: And some of these are projects within the company. So what's the structure of the industry? We have huge expenditures on R&D, I think more than any other sector, as a percent of revenue, we'll spend almost 25% of sales this year.

[译文] [Host]: 其中一些是公司内部的项目。那么这个行业的结构是怎样的？我们在研发上有巨大的支出，我想比任何其他行业都多，按收入百分比计算，我们今年将花费近25%的销售额。

[原文] [Dave Ricks]: On R&D.

[译文] [Dave Ricks]: 在研发上。

[原文] [Host]: I like your way of putting it that you spend more on medical R&D than Germany does.

[译文] [Host]: 我喜欢你这种说法：你们在医疗研发上的投入比德国还要多。

[原文] [Dave Ricks]: Yes, yeah, we're at the nation state level. It'll be, yeah, $14 billion this year. Total NIH, which is the biggest thing on earth that spends money, is 40. So that's—

[译文] [Dave Ricks]: 是的，没错，我们处于“民族国家”的级别。今年大概是140亿美元。NIH（美国国立卫生研究院）的总预算——那是地球上花钱最多的机构——是400亿。所以那是——

[原文] [Host]: It's up there.

[译文] [Host]: 已经相当接近了。

[原文] [Dave Ricks]: It's getting close, yeah. But some of those are projects we've been working on it for a while and now we have a data set, now we need to make a decision to go to the final stage. The final stage of testing, the average drug costs $3.5-4 billion to make. More than 60% of that is the last step. So that call is the big one.

[译文] [Dave Ricks]: 越来越接近了，是的。但其中一些是我们已经研究了一段时间的项目，现在我们有了一组数据，需要决定是否进入最后阶段。在测试的最后阶段——制造一款药物的平均成本是35到40亿美元。这其中超过60%的成本都在这最后一步。所以那个决策是重头戏。

[原文] [Dave Ricks]: The earlier ones of, like, go forward, okay, it's a lot of small things that add up. You can waste a lot of money if you do that poorly, but, you know, there's a portfolio, so that's unlikely. But usually we're carrying five to 10 projects in the latest phase and those are—

[译文] [Dave Ricks]: 早期的决策，比如“继续推进”，好吧，那是由很多小事情累积起来的。如果你做得不好，可能会浪费很多钱，但是，你知道，因为有一个投资组合（portfolio），所以那种情况不太可能发生。但通常我们在最新阶段会同时进行5到10个项目，而那些是——

[原文] [Host]: And so you're saying like the phase III trial—

[译文] [Host]: 所以你是说像三期临床试验——

[原文] [Dave Ricks]: Phase III, exactly. That's the question. What to test it in, how to test it, what's the design of that, go/no-go, against that criteria. And that stage, yeah, is going to be burning a billion plus a year. So it's a big investment.

[译文] [Dave Ricks]: 三期，没错。这就是问题所在。在什么人群中测试、如何测试、设计方案是什么、根据标准决定做还是不做。而那个阶段，是的，每年将烧掉十亿美元以上。所以这是巨大的投资。

[原文] [Host]: Per program.

[译文] [Host]: 每个项目。

[原文] [Dave Ricks]: Yeah, and, of course, the returns on most drugs that make it through that are not positive. So it's not just can you get through that, but will you produce something useful enough to create excess value for society but also the company to keep the whole thing running? That's the exercise.

[译文] [Dave Ricks]: 是的，而且，当然，大多数通过那个阶段的药物回报都不是正的。所以问题不仅仅是你能不能通过测试，而是你能否生产出足够有用的东西，既能为社会创造超额价值，又能让公司保持运转？这就是我们要做的功课。

章节 4：临床试验的经济账：4万美元一个病人？ (The Economics of Clinical Trials: $40k Per Patient?)

📝 本节摘要：

主持人指出一个令人咋舌的数据：临床试验的中位成本已高达每位患者4万美元，这几乎接近美国人的年收入中位数。Dave Ricks详细拆解了这一数字背后的逻辑：为了消除实验变量，药企必须“接管”患者的全部医疗护理，并支付高额溢价以确保标准治疗的一致性。他还剖析了美国临床试验参与率极低（仅4%）的结构性原因——不仅因为美国现有的标准治疗已经足够好，导致患者缺乏“试药”的动力，还因为顶尖医疗机构（如MD Anderson）过于拥挤，且伦理审查体系（IRB）过于分散，导致效率低下。

[原文] [Host]: Okay, so to this point, the dynamics and the funding of clinical trials determine so much of the portfolio dynamics for you. I think anyone who comes across these clinical trial figures and mechanics asks themselves, "Why?" How could this be?

[译文] [Host]: 好的，说到这里，临床试验的动态和资金在很大程度上决定了你们的投资组合动态。我想任何看到这些临床试验数据和运作机制的人都会问自己：“为什么？”怎么会这样？

[原文] [Dave Ricks]: Yes.

[译文] [Dave Ricks]: 是的。

[原文] [Host]: So I looked at— It's a great question. I looked at the numbers. So apparently the median clinical trial enrollee, it now costs $40,000. You know, the median US wage is $60,000. So we're talking two thirds. Why and why couldn't it be a 10th or a hundredth of what it is?

[译文] [Host]: 所以我看了——这是个好问题。我看了那些数字。显然，现在每位临床试验受试者的中位成本是4万美元。你知道，美国人的中位工资是6万美元。所以我们说的是三分之二的水平。为什么会这样？为什么不能是现在的十分之一或百分之一呢？

[原文] [Dave Ricks]: Yeah, brilliant question, and one we've spent a lot of time working on. We've done a lot of things to improve the drug development process. So taking a systems approach. And I think one of the reasons Lilly has probably the highest return on investment in R&D in the industry is because not the picking of winners and losers, but actually the process by which we run it. I think that's at least as valuable as what we've done. And we can come back to that if you want.

[译文] [Dave Ricks]: 是的，非常精彩的问题，我们也在这上面花了很多时间。为了改进药物开发流程，我们做了很多事情。也就是采取系统性的方法。我认为礼来之所以拥有行业内最高的研发投资回报率，原因之一不在于挑选赢家和输家，而实际上在于我们运作它的流程。我认为这至少与我们所做的成果一样有价值。如果你愿意，我们可以回过头来谈谈这个。

[原文] [Dave Ricks]: But the piece we've really not moved is the enrollment of clinical trials, this is going to sound super arcane when I go through it, and the cost, which is escalating about 7%-8% over the last decade. That's about the same as the healthcare system. And that's not an accident.

[译文] [Dave Ricks]: 但我们真正没有撼动的部分是临床试验的招募——当我详细讲的时候这听起来会非常晦涩难懂——以及成本，过去十年成本每年上涨约7%到8%。这与医疗系统的涨幅大致相同。这绝非巧合。

[原文] [Dave Ricks]: When people go, "Why does a trial cost so much?" Well, we're taking the sickest slice of the healthcare system that are costing the most and we're ingesting them, we're taking them out of the healthcare system and putting them in a clinical trial. Typically we pay for all care. So we are literally running the healthcare system for those individuals.

[译文] [Dave Ricks]: 当人们问，“为什么试验成本这么高？”嗯，我们选取的是医疗系统中病情最重、花费最高的那部分人群，我们将他们“摄入”，即把他们从医疗系统中接出来，放入临床试验中。通常我们会支付所有的护理费用。所以，我们实际上是在为这些人运行整个医疗系统。

[原文] [Dave Ricks]: And that is, in some ways, for control, because you want to have the best standard of care, so your experiment is properly conducted and it's not just left to the whims of hundreds of individual doctors and people in Ireland versus the US getting different background therapies. So you standardize that, that costs money because you're sort of leveling up a lot of things.

[译文] [Dave Ricks]: 这在某种程度上是为了控制变量，因为你想要最好的标准治疗，这样你的实验才能正确进行，而不是任由数百名个体医生的突发奇想摆布，或者让爱尔兰和美国的患者接受不同的背景疗法。所以你要将其标准化，这需要花钱，因为你在某种程度上是在“升级（leveling up）”很多东西。

[原文] [Dave Ricks]: But then also, in some ways, you're paying a premium to both get the treating physicians and having a great care to get the patient. We don't offer them remuneration, but they get great care, an inducement to be in the study because you're subjecting yourself quite often, not all the case, but to something other than the standard of care, either placebo or this, or in more specialized care, often it's standard care plus X where X could actually be doing harm, not good. So people have to go into that in a blinded way. And I guess the consideration is you'll get the best care.

[译文] [Dave Ricks]: 但从另一方面来说，你也支付了溢价，既是为了获得治疗医生，也是为了让患者得到极好的护理。我们不给他们（患者）报酬，但他们得到了极好的护理，这是参与研究的一种诱因。因为你经常——虽然不全是这样——要让自己接受标准治疗以外的东西，要么是安慰剂，要么是这个新药，或者在更专业的护理中，通常是“标准治疗加X”，而这个X实际上可能带来伤害而非好处。所以人们必须在不知情（盲态）的情况下参与。我想这种交换条件就是你会得到最好的照顾。

[原文] [Host]: Of the $40,000, how much of that should I look at as inducement and encouragement for the patient and how much should I look at it as the cost of doing things given the regulatory apparatus that exists?

[译文] [Host]: 在这4万美元中，有多少应被视为对患者的诱导和鼓励，又有多少应被视为在现有监管机制下做事的必要成本？

[原文] [Dave Ricks]: The patient part is like the level up part and I would say 20%-30% of the cost of studies typically would be this. So you're buying the best standard of care. You're not getting something less. That's medicine costs, you're getting more testing, you're getting more visits.

[译文] [Dave Ricks]: 患者部分就像是“升级”的那部分，我想说通常研究成本的20%到30%是这一块。所以你买的是最好的标准治疗。你得到的不会打折扣。那是药物成本，你会得到更多的检测，更多的就诊。

[原文] [Dave Ricks]: And then there is a premium that goes to institutions, not usually to the physician, the institution, to pay for the time of everybody involved in it plus something. We read a lot about it in the NIH cuts, the 60% Harvard markup or whatever. There's something like that in all clinical trials too. Overhead, coverage, whatnot. But it's paying for things that aren't in the trial.

[译文] [Dave Ricks]: 然后还有一笔支付给机构的溢价——通常不是给医生，而是给机构——用来支付所有参与人员的时间，外加一些额外费用。我们在关于削减NIH（经费）的新闻里经常读到这个，比如“60%的哈佛加价（Harvard markup）”之类的。所有的临床试验中也有类似的情况。管理费、覆盖范围等等。但这实际上是在为试验之外的事情买单。

[原文] [Host]: US healthcare is famously the most expensive in the world. Do you run trials outside the US?

[译文] [Host]: 众所周知，美国医疗是世界上最昂贵的。你们在美国以外的地方进行试验吗？

[原文] [Dave Ricks]: Yeah, actually most. Most of it, yeah.

[译文] [Dave Ricks]: 是的，实际上大部分都是。大部分，是的。

[原文] [Host]: So, yeah.

[译文] [Host]: 所以，是的。

[原文] [Dave Ricks]: I mean, we want to actually do more in the US. This is a problem, I think, for our country. Like, take cancer care where you think, "Okay, what's the one thing the US system is really good at?" Like if I had cancer, I'd come to the US. That's definitely true.

[译文] [Dave Ricks]: 我的意思是，我们其实想在美国做更多。我认为这对我们要国家来说是个问题。比如拿癌症治疗来说，你会想，“好吧，美国体系真正擅长的一件事是什么？”比如如果我得了癌症，我会来美国。这绝对是真的。

[原文] [Dave Ricks]: But only 4% of patients who have cancer in the US are in clinical trials, whereas in Spain and Australia, it's over 25%. And some of that is because they've optimized the system so it's easier to run and then enroll, which I'd like to get to, people in the trials. But some of it is also that the background of care isn't as good. So that level up inducement is better for the patient and the physician. Here, the standard's pretty good. So people are like, "Meh, do I want to do something where there's extra visits and travel time?"

[译文] [Dave Ricks]: 但是在美国，只有4%的癌症患者参与临床试验，而在西班牙和澳大利亚，这个比例超过25%。部分原因是因为他们优化了系统，使其更容易运行和招募——这一点我稍后想谈谈——更容易让人进入试验。但部分原因也是因为那些地方的基础护理水平没那么好。所以那种“升级”带来的诱因对患者和医生来说都更有吸引力。而在美国，标准已经很好了。所以人们会觉得，“啧，我真的想做这种需要额外就诊和花费路上时间的事情吗？”

[原文] [Dave Ricks]: There's another problem in the US, which is we have really good standards of care but also quite different performing systems and we often want to place our trials in the best performing systems that are famous, like MD Anderson or the Brigham, and those are the most congested with trials and therefore they're the slowest and most expensive. So there's a bit of a competition for place that goes on as well.

[译文] [Dave Ricks]: 在美国还有另一个问题，就是我们拥有非常好的标准治疗，但各医疗系统的表现却差异巨大。我们通常希望把试验放在那些著名的、表现最好的系统中，比如MD Anderson（MD安德森癌症中心）或Brigham（布列根和妇女医院），但那些地方也是试验最扎堆（congested）的地方，因此它们也是最慢和最贵的。所以这里面也存在一种对“地盘”的竞争。

[原文] [Dave Ricks]: But, overall, I would say, like, in our diabetes and cardiovascular trials, many, many more patients are in our trials outside the US than in and that really shouldn't be other than cost of the system, and to some degree, the tuning of the system, like I mentioned with Spain and Australia, toward doing more clinical trials.

[译文] [Dave Ricks]: 但总的来说，我想说，比如在我们的糖尿病和心血管试验中，美国以外的参与患者比美国国内要多得多得多，而这真的不应该是这样，除了系统成本的原因，还在一定程度上取决于系统的“调校”，就像我提到的西班牙和澳大利亚，它们更倾向于开展更多的临床试验。

[原文] [Dave Ricks]: For instance, like, here in the US, everywhere, you get ethics clearance, we call IRB. The US has a decentralized system, so you have to go to every system you're doing a study in. Some countries, like Australia, have a single system. So you just have one stop and then the whole country is available to recruit, those types of things.

[译文] [Dave Ricks]: 举个例子，比如在美国，无论在哪里，你都要获得伦理许可，我们称之为IRB（机构审查委员会）。美国有一个去中心化的系统，所以你必须去每一个你开展研究的系统中申请。有些国家，比如澳大利亚，有一个单一的系统。所以你只需要过这一关，然后整个国家都可以进行招募，诸如此类的事情。

章节 5：泰勒·斯威夫特效应与招募瓶颈 (The Taylor Swift Effect & The Enrollment Bottleneck)

📝 本节摘要：

药物开发中最耗时的环节往往不是科学实验，而是漫长的“等待患者”。Dave Ricks用一个生动的类比指出了行业的痛点：泰勒·斯威夫特（Taylor Swift）的演唱会门票能在几秒钟内售罄，而制药公司却难以填满一个拥有庞大潜在患者群体的阿尔茨海默病临床试验。为了打破这种“守株待兔”的低效模式，礼来正在尝试主动出击：利用电子健康记录（如针对Lp(a)胆固醇项目）精准定位并联系患者，以及采用“直接面向患者”的远程试验模式。Ricks分享了一个惊人的成功案例：通过这种去中心化的新模式，他们仅依靠一名研究员就筛选了8万名志愿者，完成了史上招募速度最快的阿尔茨海默病预防研究。

[原文] [Host]: You said you want to talk about enrollment?

[译文] [Host]: 你说你想谈谈招募的问题？

[原文] [Dave Ricks]: Yeah, yeah, it's fascinating. So drug development time in the industry is about 10 years in the clinic, a little less right now. We're running a little less than seven at Lilly. So that's the optimization I spoke about.

[译文] [Dave Ricks]: 是的，是的，这很值得玩味。行业内的药物临床开发时间大约是10年，现在稍微短一点。我们在礼来大约控制在不到7年。这就是我之前提到的优化。

[原文] [Dave Ricks]: But actually, half of that seven is we have a protocol open. That means it's an experiment we want to run. We have sites trained, they're waiting for patients to walk in their door and to propose, "Would you like to be in the study," but we don't have enough people in the study.

[译文] [Dave Ricks]: 但实际上，这7年里有一半时间是因为我们开启了一个方案。这意味着这是一个我们想运行的实验。我们培训好了站点，他们在等待患者走进门，然后提议问：“你想参加这项研究吗？”但我们研究中的人手（患者）不够。

[原文] [Dave Ricks]: So you're in the serial process, diffuse serial process, waiting for people to show up and you think, "Wow, that seems like we could do better than that. If Taylor Swift can sell out a concert in a few seconds, why can't I fill an Alzheimer's study? There seem to be lots of patients."

[译文] [Dave Ricks]: 所以你陷入了一个串行的过程，一个分散的串行过程，等着人们出现，你会想，“哇，看来我们可以做得比这更好。如果泰勒·斯威夫特（Taylor Swift）能在几秒钟内卖光一场演唱会的票，为什么我填不满一个阿尔茨海默病的研究？明明似乎有很多患者。”

[原文] [Dave Ricks]: But that's healthcare. It's very tough. We've done some interesting things recently to work around that. One thing that's an idea that partially works now is culling existing databases and contacting patients. Proactive outreach.

[译文] [Dave Ricks]: 但这就是医疗保健。非常艰难。最近我们做了一些有趣的事情来解决这个问题。其中一个现在部分奏效的想法是筛选现有的数据库并联系患者。即主动出击（Proactive outreach）。

[原文] [Host]: Right, where you have, like, their lab values from, where before there wasn't a treatment, now there is one being studied, would you like to be a part of it?

[译文] [Host]: 对，比如你有他们的实验室数值，以前那里没有治疗方法，现在有一个正在研究中，你问他们愿不愿意参与？

[原文] [Dave Ricks]: That's something we're doing now with our Lp program. That's a cholesterol subtype where there was nothing to do about it. A lot of people have had it tested and it's high. You could say, "Hey, you're high. Would you like to do something now?"

[译文] [Dave Ricks]: 这正是我们现在在Lp（脂蛋白）项目中做的事情。那是一种胆固醇亚型，以前对此束手无策。很多人做过检测，数值很高。你可以说：“嘿，你的指标很高。你现在想做点什么吗？”

[原文] [Dave Ricks]: But it's still a lot to be done there and the data that's sitting in electronic health records in our country is very poorly organized. So it would be good to optimize that.

[译文] [Dave Ricks]: 但这方面仍有很多工作要做，而且我们国家电子健康记录中的数据组织得非常糟糕。所以优化这一点会很好。

[原文] [Dave Ricks]: I think the other is actually just go directly to the patients. So who has the most interest? It's usually the patient. And then physicians and their institution may not be in the trial or they might not be interested in spending much time on this and people—

[译文] [Dave Ricks]: 我认为另一种方法实际上是直接面向患者。谁最感兴趣？通常是患者。而医生和他们的机构可能并没有参与试验，或者他们可能对在这上面花太多时间不感兴趣，而人们——

[原文] [Host]: That's kind of what I want. I want to get an email, as you say, you know, the system knows, you know, my health data and what conditions I have and so forth, and be told that a package will be arriving tomorrow with a drug.

[译文] [Host]: 这正是我想要的那种。就像你说的，我希望收到一封邮件，系统知道我的健康数据、我有什么病症等等，然后告诉我明天会有一个装着药的包裹送到。

[原文] [Host]: I can take the drug if I want to, if I want to participate in this trial. You can include whatever disclosures. And, you know, some nice person will come every month or whatever and take—

[译文] [Host]: 如果我想，如果我想参加这个试验，我就能服用这种药。你可以附上任何免责声明。然后，你知道，每个月会有个和善的人过来，或者不管怎样，来取——

[原文] [Dave Ricks]: Or just telephonically visit you.

[译文] [Dave Ricks]: 或者只是通过电话回访你。

[原文] [Host]: Yeah. Take my vitals, exactly, and measure my blood pressure and what have you. Are all these intermediaries in the systems in, you know, the hospitals and so forth, are they required intrinsically for the kinds of trials you want to run?

[译文] [Host]: 是的。测量我的生命体征，没错，量血压之类的。系统里的所有这些中间人——比如医院里的那些等等——对于你们想进行的这类试验来说，本质上是必须的吗？

[原文] [Dave Ricks]: Obviously varies a little bit on the condition or the drug. Depends on the disease.

[译文] [Dave Ricks]: 显然这取决于病情或药物。取决于疾病。

[原文] [Host]: Yeah, yeah. Right, right. Well, I guess, yeah, so how much of it is there in fact intrinsically required given, you know, the characteristics of the condition and how much is it this is how things are done?

[译文] [Host]: 是的，是的。对，对。好吧，我想，是的，考虑到病情的特征，事实上有多大程度上是本质上需要的？又有多少仅仅是因为“事情一贯是这么做的”？

[原文] [Dave Ricks]: Yeah, what you described is actually a great vision for where we want to go. We've executed one of these at scale, which is fully enrolled, which was our Alzheimer's prevention study.

[译文] [Dave Ricks]: 是的，你描述的实际上正是我们想要实现的一个伟大愿景。我们已经规模化地执行过一次这样的试验，并且已经完全招募满员了，那是我们的阿尔茨海默病预防研究。

[原文] [Dave Ricks]: It's a more complicated medicine. It's an infused medicine. But we ran this with one investigator in the United States and we screened over 80,000 people.

[译文] [Dave Ricks]: 那是一种比较复杂的药物。是一种输液药物。但我们在美国仅用了一名研究员（investigator）就运行了这个项目，并且我们筛选了超过80,000人。

[原文] [Dave Ricks]: By the way, it's the fastest accrued Alzheimer's study in history, even though it's pre-Alzheimer's. It's people with the amyloid precursor protein, but not dementia. It's fully enrolled.

[译文] [Dave Ricks]: 顺便说一句，这是历史上招募速度最快的阿尔茨海默病研究，尽管它是针对阿尔茨海默病前期的。针对的是那些有淀粉样前体蛋白但尚未痴呆的人群。已经完全招募满了。

[原文] [Dave Ricks]: We've treated people, actually no one's left on treatment. We're just watching them now, because the treatment's a nine-month course to deplete amyloid and see if that can prevent the symptoms. So that was a very successful trial. Just what you said. They got instructions to be in the study.

[译文] [Dave Ricks]: 我们已经治疗了患者，实际上现在没有人还在治疗期了。我们现在只是在观察他们，因为治疗是一个九个月的疗程，目的是清除淀粉样蛋白，看看是否能预防症状。所以那是一个非常成功的试验。就像你说的。他们收到了参与研究的指引。

[原文] [Dave Ricks]: There was a televisit. They got some diagnostic tests, blood-based, that went in and said, "Okay, this is sort of an indicator you might have high amyloid," then you can go to get a PET scan, and if that was positive, you could be enrolled in the study. Pretty successful.

[译文] [Dave Ricks]: 有远程问诊。他们做了一些基于血液的诊断测试，结果显示，“好的，这是一个指标，显示你可能有高淀粉样蛋白”，然后你可以去做个PET扫描，如果是阳性，你就可以加入研究。相当成功。

[原文] [Dave Ricks]: So we'd like to replicate that. I think one very interesting thing in the future of medicine is that I think we will have a lot more preventative medicines in the future. And I think this type of study in particular is well suited to prevention because you have sort of the people who are worried about their wellness, so they're motivated.

[译文] [Dave Ricks]: 所以我们想复制这种模式。我认为医学未来的一个非常有趣的事情是，我们将来会有更多的预防性药物。我认为这类研究特别适合预防领域，因为你会遇到那些担心自己健康状况的人，所以他们有动力。

[原文] [Dave Ricks]: They have means. They're in the middle of their life. They're working. They don't have complications of comorbidities and so forth. They want to be in the study, and I think they would like to prevent terrible conditions like Alzheimer's. So that's an exciting new chapter we can push.

[译文] [Dave Ricks]: 他们有经济能力。他们处于中年。他们在工作。他们没有并发症的困扰等等。他们想参加研究，我想他们也愿意预防像阿尔茨海默病这样可怕的疾病。所以这是一个我们可以推进的令人兴奋的新篇章。

章节 6：医学界的乔丹与监管的“单向棘轮” (The Michael Jordan of Medicine & The Regulatory Ratchet)

📝 本节摘要：

本节从向传奇人物Paul Janssen（杨森）致敬开始，他被誉为医学界的“迈克尔·乔丹”。随后，对话转向了一个深刻的行业议题：为何药物研发过程如此官僚且昂贵？Dave Ricks认为这是一种“社会选择”，源于过去由于检测能力不足而导致的安全事故（如默克的Vioxx和GSK的药物撤回事件）。这些危机导致了长达十年的“研发寒冬”，并确立了极其严苛的心血管风险排除标准。Ricks形象地将其描述为监管的“棘轮效应”——规则往往只增不减。虽然这在无意中为当前的GLP-1药物构建了极高的竞争护城河，但也引发了关于技术进步是否应促使监管“重新评估”的反思。

[原文] [Host]: So you know Paul Janssen?

[译文] [Host]: 你知道Paul Janssen（保罗·杨森）吗？

[原文] [Dave Ricks]: Yeah.

[译文] [Dave Ricks]: 是的。

[原文] [Host]: Yeah, yeah. So- Explain who Paul Janssen is. Come on.

[译文] [Host]: 是的，是的。那么——解释一下Paul Janssen是谁。来吧。

[原文] [Host]: Paul Janssen, as I understand it, was behind the discovery, invention, what have you, of more medications than any other single—

[译文] [Host]: 据我所知，Paul Janssen所发现、发明（或者随便你怎么称呼）的药物数量，比任何其他单个人都要多——

[原文] [Dave Ricks]: I think a Belgian guy.

[译文] [Dave Ricks]: 我想是个比利时人。

[原文] [Host]: Yeah, exactly, yes, yes. I think it's— Who invented a number of—

[译文] [Host]: 对，没错，是的，是的。我想是——他发明了大量的——

[原文] [Dave Ricks]: 79 or 80 approved—

[译文] [Dave Ricks]: 79或80种获批药物——

[原文] [Host]: The MVP of medicine.

[译文] [Host]: 医学界的MVP（最有价值球员）。

[原文] [Dave Ricks]: Michael Jordan of the NIH.

[译文] [Dave Ricks]: NIH（美国国立卫生研究院）级别的迈克尔·乔丹。

[原文] [Host]: Beyond MVP. Yes. Okay, so amazing guy. When some outsider comes to the clinical trial process and system and just the development pipeline overall, maybe they naively think, "Wow, this seems so torturous, so expensive, so bureaucratic," what have you. But that's how it's gotta be.

[译文] [Host]: 超越MVP。是的。好吧，一个了不起的人。当一些外行看到临床试验流程、系统以及整个开发管线时，也许他们会天真地想：“哇，这看起来太折磨人了，太昂贵了，太官僚了，”诸如此类。但事情就得是这样。

[原文] [Dave Ricks]: But that's how it's gotta be.

[译文] [Dave Ricks]: 但事情就得是这样。

[原文] [Host]: You know, or if they think it can be otherwise, you might think that they're naive, right? There's a video interview with Janssen from, I think it's from the '90s, it's from, you know, quite a while ago, I mean, he's dead now, where he's recounting the history of his career. He started the company in 1953.

[译文] [Host]: 你知道，或者如果他们认为可以不这样，你可能会觉得他们很天真，对吧？有一段Janssen的视频采访，我想是90年代的，是很久以前的了——我是说，他现在已经去世了——他在那里回顾了自己的职业生涯历史。他在1953年创办了那家公司。

[原文] [Host]: We could go back to doing it the way we used to and it's kind of a, it's a societal choice to make it so bureaucratic.

[译文] [Host]: 我们本可以回到过去的做法，但这有点像是——把它变得如此官僚化是一种社会选择。

[原文] [Dave Ricks]: I guess it's an explicit and implicit one. The explicit part is through time, there have been accidents and nothing is perfect. We probably have 2,000 manmade approved medicines versus natural products or vitamins or other things and maybe 400 unique mechanisms. So there's clustering.

[译文] [Dave Ricks]: 我想这既是显性的也是隐性的选择。显性的部分是，随着时间的推移，出现过事故，没有任何东西是完美的。我们大概有2000种获批的人造药物（相对于天然产物、维生素或其他东西），大概涉及400种独特的机制。所以存在聚集效应。

[原文] [Dave Ricks]: Within those, there have been problems and there's also been problems that turned out not to be problems. And so our detection ability is flawed. Because of that, I think each time that occurs, there was intervention in the system, which is sort of a global consensus, but mostly the developed economies kind of harmonize their systems either directly or indirectly to say, "Oh, no, let's require more information or rebalance the risk-benefit."

[译文] [Dave Ricks]: 在这些药物中，出现过问题，也有过那种后来证明并非问题的问题。所以我们的检测能力是有缺陷的。正因为如此，我认为每当这种情况发生时，系统就会进行干预，这算是一种全球共识，但主要是发达经济体直接或间接地协调它们的系统，说：“哦，不，让我们要求更多的信息，或者重新平衡风险与收益。”

[原文] [Dave Ricks]: We've had this ratchet. Have we gone too far? I think that it's a function of what the technology is at the moment. And I think in past times, yes.

[译文] [Dave Ricks]: 我们经历了这种“棘轮效应”（注：指只能单向转动，意指规则只增不减）。我们是否做得过火了？我认为这是取决于当时的具体技术水平。我觉得在过去，是的。

[原文] [Dave Ricks]: You can take the 2000s in the US where there were two big controversial drug approvals that were later retracted, the Vioxx situation with Merck and then Avastin from GSK. These were both drugs that were for different uses, pain and diabetes, but through a detection requirement that the agencies, because now we have electronic records, we can look at things, picked up what they thought was a trace of risk for both, cardiovascular risks, and intervened with labeling and escalation until finally both companies actually removed the products from the market, withstood billions of dollars in product liability suits, only to find later under a different analysis that there was nothing to be seen there. Both of them.

[译文] [Dave Ricks]: 你可以看看2000年代的美国，当时有两个巨大的争议性药物批准后来被撤回了：默克（Merck）的Vioxx事件，以及GSK的Avastin（注：此处口误，结合下文应指Avandia/文迪雅）。这是两种用途不同的药物，分别用于止痛和糖尿病，但通过监管机构的检测要求——因为现在我们有了电子记录，可以查看数据——他们在这两种药中都发现了他们认为是风险迹象的东西，即心血管风险，并通过标签和升级措施进行干预，直到最后两家公司实际上都将产品撤出了市场，承受了数十亿美元的产品责任诉讼，结果后来在另一种分析下才发现，那里其实什么问题都没有。两者都是。

[原文] [Dave Ricks]: And I think there's like an ascertainment bias problem with these studies. There's also who was looking at this data. But that caused a 10-year chill in drug development.

[译文] [Dave Ricks]: 我认为这些研究存在某种确认偏差（ascertainment bias）问题。还有就是谁在看这些数据的问题。但这导致了药物开发领域长达10年的寒冬。

[原文] [Dave Ricks]: And the Avandia one we know well, we work in diabetes, actually caused a policy change. And the policy change was you must rule out cardiovascular risk prior to market entry.

[译文] [Dave Ricks]: 那个Avandia（文迪雅）的案例我们很熟悉，因为我们从事糖尿病领域，它实际上导致了一项政策变更。这项政策变更是：你必须在进入市场之前排除心血管风险。

[原文] [Dave Ricks]: And as you may know, some conditions like diabetes have a more continuous variable you're measuring and so studies can be short and cheaper, glucose levels. Other studies like cardiovascular event studies are not a continuous variable, it's a binary variable, and you have to wait for natural history to occur to pile up enough variables to have a statistical difference.

[译文] [Dave Ricks]: 如你所知，像糖尿病这样的疾病，你测量的是一个更连续的变量（血糖水平），所以研究可以很短且更便宜。而像心血管事件研究，那不是连续变量，是二元变量（发病或未发病），你必须等待自然病程发生，积累足够的变量才能得出统计学差异。

[原文] [Dave Ricks]: Those are four to five-year undertakings. So there, you just bought four or five years of extra time before you could get any new diabetes medication. We got better at doing them, but that was expensive. Now, has that... That's the explicit.

[译文] [Dave Ricks]: 那些都是需要四到五年的任务。所以在那里，你为了获得任何新的糖尿病药物，凭空增加了四到五年的额外时间。我们后来更擅长做这些研究了，但那是昂贵的。现在，这是否……那是显性的部分。

[原文] [Dave Ricks]: The implicit is the regulatory problem. There must be a name for this problem some smart person's given it, but regulatories are added but never taken away. So the regulation is still there.

[译文] [Dave Ricks]: 隐性的部分是监管问题。肯定有个聪明人给这个问题起过名字，就是监管规定总是被添加，却从未被取消。所以那些规定依然存在。

[原文] [Dave Ricks]: Now, by happy accident, we are all now really pleased with, like, incretins like our tirzepatide to run them 'cause they frequently demonstrate massive benefit on cardiovascular and, in some ways, it creates a barrier to entry for the next low-cost Chinese program or whatever 'cause it's this big expensive thing you have to—

[译文] [Dave Ricks]: 现在，出于某种幸运的巧合，我们实际上都很乐意为像我们的替尔泊肽（tirzepatide）这样的肠促胰素药物运行这些测试，因为它们经常在心血管方面显示出巨大的益处。而且，在某种程度上，这为下一个低成本的中国项目或其他什么项目建立了进入壁垒，因为这是一个巨大的、昂贵的、你必须完成的事情——

[原文] [Host]: As with many regulatory—

[译文] [Host]: 就像许多监管一样——

[原文] [Dave Ricks]: Yeah, exactly. Right. So is it right? No, we're imperfect as people and certainly as decision-makers at a collective level. I would also say the technology for seeing early signals has changed and improved, including computer technology, and it's probably worth a reassessment.

[译文] [Dave Ricks]: 是的，没错。对。但这正确吗？不，作为人我们是不完美的，作为集体层面的决策者当然也不完美。我也想说，用于观察早期信号的技术已经改变和改进了，包括计算机技术，这可能值得重新评估。

章节 7：为预防买单与打破“在位者”魔咒 (Paying for Prevention & The Incumbency Problem)

📝 本节摘要：

对话转向了预防性医疗的经济学悖论。主持人提出了一个尖锐的现实问题：既然GLP-1减肥药的经济回报（如避免心脏病）需要长期体现，而员工或投保人的流转率很高，保险公司为何要在短期内为此买单？Dave Ricks反驳了这种“短期主义”担忧，指出最新数据表明，药物带来的总医疗成本节省其实在“两年内”就能实现盈亏平衡。他特别引用了ICER（一家通常对药企持批评态度的监督机构）的报告，该报告意外地认定Zepbound即便在当前价格下也是“具有成本效益”的。此外，Ricks深刻剖析了医疗体系中的“在位者问题（Incumbency Problem）”：新疗法往往面临极其严苛的审查，而那些早已确立但可能低效的“标准疗法”却极少被重新评估。

[原文] [Host]: Paying for prevention, you were going to ask.

[译文] [Host]: 关于为预防买单，你刚才正要问。

[原文] [Host]: Yeah, let's talk about that because say with, you know, GLPs in the weight loss context, they economically pay off over a very long time horizon, but if you're looking at a short time horizon of an insurer or an employer, they don't necessarily, and so that's created this challenge for reimbursement where, you know, not as many people reimburse GLPs for weight loss as you think would be rational.

[译文] [Host]: 是的，让我们谈谈这个。因为比如说在减肥情境下的GLP类药物，它们在经济上的回报周期非常长，但如果你从保险公司或雇主的短期时间范围来看，这笔账未必算得过来。所以这就造成了报销方面的挑战，导致报销GLP减肥药的人数并没有像你认为理性的那样多。

[原文] [Dave Ricks]: Yep.

[译文] [Dave Ricks]: 是的。

[原文] [Host]: That just will always be the case with prevention. And so how do you actually develop drugs that are commercializable and reimbursable?

[译文] [Host]: 预防性医疗的情况总是如此。那么，你们究竟如何开发既具商业价值又能获得报销的药物呢？

[原文] [Dave Ricks]: Yeah, well, in the obesity case, I'll take a little bit issue with your first assertion and then add two other problems. The data actually is becoming more clear that within actually a two-year timeframe, and I hope at Stripe, you reimburse these medicines for your patients, or for your employees. Within two years, you can break even basically on total medical costs.

[译文] [Dave Ricks]: 是的，嗯，在肥胖症这个案例上，我对你的第一个断言稍微有点不同意见，然后我再补充两个其他问题。数据实际上正变得越来越清晰，在短短两年的时间框架内——我希望在Stripe，你们为你们的患者，或者说为你们的员工报销这些药物——在两年内，你基本上可以在总医疗成本上实现盈亏平衡。

[原文] [Dave Ricks]: So there's this group called ICER, which is funded by someone who hates our industry and the insurance companies, and they analyze all new drugs and usually seeking to prove that they're not worth it. That's sort of their mission in life.

[译文] [Dave Ricks]: 有这么一个叫ICER（临床与经济评价研究所）的组织，它是由痛恨我们行业的人和保险公司资助的。他们分析所有新药，通常旨在证明这些药不值那个价。这算是他们的人生使命。

[原文] [Dave Ricks]: They just analyzed our medicine, tirzepatide and semaglutide, and they said, "Actually, they're both cost effective at current pricing."

[译文] [Dave Ricks]: 他们刚刚分析了我们的药物——替尔泊肽（tirzepatide）和索马鲁肽（semaglutide），结论是：“实际上，按当前定价，它们都具有成本效益。”

[原文] [Dave Ricks]: In fact, Zepbound, or tirzepatide, was, the threshold they have is to save a hundred thousand dollars per person per year in downstream health costs, and it was twice as effective as that at the current pricing.

[译文] [Dave Ricks]: 事实上，Zepbound（即替尔泊肽）的表现是——他们设定的门槛是每人每年在下游健康成本上节省10万美元——而在当前定价下，它的效果是这个门槛的两倍。

[原文] [Dave Ricks]: And the current pricing isn't going to stay, let's be honest. There'll be more competition. The government wants to lower our prices. So, you know, I think we're in a good place there.

[译文] [Dave Ricks]: 而且老实说，当前的定价不会一直维持下去。会有更多的竞争。政府也想压低我们的价格。所以，你知道，我认为我们在这一点上处于有利位置。

[原文] [Dave Ricks]: Now, the two other problems are there's sort of this incumbency problem in healthcare, like many things, but particularly in healthcare, where the last thing in is scrutinized the most and the base stack of services and products we use is never revisited. It becomes standard of care.

[译文] [Dave Ricks]: 那么，另外两个问题是，医疗领域存在某种“在位者问题（incumbency problem）”，很多领域都有，但在医疗领域尤甚：也就是最新进来的东西受到最严格的审查，而我们使用的基础服务和产品堆栈却从未被重新审视。它们成了“标准疗法”。

[原文] [Dave Ricks]: But displacing that in most therapeutic spaces and in the healthcare system in general is extremely difficult. I think we suffer from that here.

[译文] [Dave Ricks]: 但在大多数治疗领域以及整个医疗体系中，要取代这些旧东西是极其困难的。我认为我们在这里就遭遇了这个问题。

[原文] [Dave Ricks]: If the first medicine we had to treat metabolic conditions was tirzepatide in 1972, I have no doubt it would be reimbursed everywhere and broadly used in the system. But they get the ratcheting effects.

[译文] [Dave Ricks]: 如果我们在1972年用来治疗代谢疾病的第一种药物就是替尔泊肽，我毫无疑问它会在各地得到报销并在系统中被广泛使用。但它们遭遇了这种“棘轮效应”。

[原文] [Dave Ricks]: But then you're just stacking on top of it and it's difficult to remove benefits, it's easy to deny new ones, and that's true in government-funded systems but also, you know, big insurers.

[译文] [Dave Ricks]: 你只是在旧的基础上不断叠加，要取消现有的福利很难，但拒绝新的福利很容易。无论是在政府资助的系统中，还是在大保险公司里，情况都是如此。

章节 8：进化的陷阱与“第二顿早餐” (The Evolutionary Trap & The "Second Breakfast")

📝 本节摘要：

话题深入到肥胖的根源与社会偏见。Dave Ricks不仅从生物进化角度为肥胖者“平反”，指出人类基因被编程为“囤积热量以抗饥荒”，这在现代食物过剩（美国人日均摄入3600卡路里）的环境下变成了一种生理陷阱。他通过数据揭示了GLP-1药物的神奇之处：它能让患者每天自然减少约800卡路里的摄入——这相当于少吃了一顿“第二早餐”。更重要的是，与让人暴躁的传统节食不同，这种药物能调节体内的激素平衡，让减肥过程不再痛苦。

[原文] [Dave Ricks]: I think the other thing that's going on with this one and why we're spending so much energy exploring, you know, real indications for comorbid diseases that go with obesity, which is so far pretty successful, is that the idea of just treating someone who's overweight or obese without any other illness, to many people I think exposes a bias we have about that particular condition.

[译文] [Dave Ricks]: 我认为这件事还有另一个层面——这也是为什么我们投入如此多精力去探索伴随肥胖的共病适应症，且目前相当成功的原因——那就是：在很多人看来，仅仅治疗一个超重或肥胖但没有其他疾病的人，暴露了我们对这种特定状况的一种偏见。

[原文] [Dave Ricks]: That if it wasn't something you could see, you might not have. But I think we are conditioned to think of someone who's overweight as someone who's not disciplined. The data does not show that actually.

[译文] [Dave Ricks]: 如果这病不是肉眼可见的，你可能就不会有这种偏见。但我认为我们已经习惯于认为，超重的人就是缺乏自律的人。然而数据实际上并不支持这一点。

[原文] [Dave Ricks]: Like our ancestors roaming the plains of whatever, the tundra of Ireland, walking across the ice bridge from Norway, were in a background of starvation and there are very few humans on earth that have a genetic background that has any limit on food consumption.

[译文] [Dave Ricks]: 就像我们的祖先，无论是在哪里的平原漫游，还是在爱尔兰的冻原，或是走过挪威的冰桥，他们都处于饥荒的背景之中。地球上极少有人类的基因背景是对食物摄入有任何限制的。

[原文] [Dave Ricks]: It's irrational. It's a wasted piece of code. It did no good. Now, today, in today's environment, we're in the flip, the complete flip, especially here in the US, where there's food everywhere we walk.

[译文] [Dave Ricks]: 那（限制食欲）是不理性的。那是一段废代码。它没有任何好处。然而在今天，在如今的环境下，我们处在一个反转、完全反转的局面中，尤其是在美国，我们走到哪里都是食物。

[原文] [Host]: I came across your stat, what would you guess the average caloric consumption per day in America is?

[译文] [Host]: 我看到了你们的一个统计数据，你猜美国人平均每天的热量摄入是多少？

[原文] [Dave Ricks]: 3,600 calories.

[译文] [Dave Ricks]: 3600卡路里。

[原文] [Host]: Yeah.

[译文] [Host]: 是的。

[原文] [Dave Ricks]: Yeah. Isn't that incredible?

[译文] [Dave Ricks]: 是的。这难道不令人难以置信吗？

[原文] [Host]: Yeah, that's a really incredible. And here's an interesting stat. When you're on our medicine, how many fewer calories do you consume on average?

[译文] [Host]: 是的，这真的太不可思议了。这里还有一个有趣的数据。当服用你们的药物时，人们平均会少摄入多少卡路里？

[原文] [Dave Ricks]: On one of the GLP-1s?

[译文] [Dave Ricks]: 在服用某种GLP-1药物的情况下吗？

[原文] [Host]: Yeah. You don't need to swing it that much to cause meaningful—

[译文] [Host]: 是的。其实不需要大幅度改变就能产生有意义的——

[原文] [Dave Ricks]: 800 calories a day.

[译文] [Dave Ricks]: 每天800卡路里。

[原文] [Host]: Oh my God. 800? Which is almost a meal.

[译文] [Host]: 天哪。800？这几乎是一顿饭的量了。

[原文] [Dave Ricks]: Yeah. If you go pull up to In-N-Out Burger—

[译文] [Dave Ricks]: 是的。如果你把车开到In-N-Out汉堡店——

[原文] [Host]: That's second breakfast right there.

[译文] [Host]: 那简直就是“第二顿早餐”（second breakfast）。

[原文] [Dave Ricks]: It's second breakfast. Exactly. So that's why people lose weight so successfully. No wonder all the food companies are so worried.

[译文] [Dave Ricks]: 就是第二顿早餐。没错。所以这就是为什么人们能如此成功地减肥。难怪所有的食品公司都那么担心。

[原文] [Dave Ricks]: And the trick, yeah, yeah. And the trick is people lose the weight and they don't feel miserable, right?

[译文] [Dave Ricks]: 诀窍在于——是的，是的。诀窍在于人们减掉了体重，而且他们并不感到痛苦，对吧？

[原文] [Dave Ricks]: So here's the thing about being obese is people, when you start to gain a little bit of weight, your set point sort of readjusts. This is the missing code we have. And there's only one direction, which is up is better.

[译文] [Dave Ricks]: 关于肥胖是这样的：当你开始增加一点体重时，你的“调定点（set point）”会某种程度上重新调整。这就是我们缺失的那段代码。它只有一个方向，那就是“涨了更好”。

[原文] [Dave Ricks]: And the more up you have actually the more hunger it creates. Hyperinsulinemia, which is a hunger-stimulating hormone. And it sort of starts to overwhelm the counterregulatory system, which is incretins, GLP-1, GIP, the ones we are making medicines around, and you're out of balance and there's no going back.

[译文] [Dave Ricks]: 而且实际上你体重越重，产生的饥饿感就越强。高胰岛素血症（Hyperinsulinemia），这是一种刺激饥饿的激素状态。它开始压倒反向调节系统——即肠促胰素、GLP-1、GIP，也就是我们要围绕其制造药物的那些东西——导致你失去平衡，无法回头。

[原文] [Dave Ricks]: And interestingly, even when people lose weight, that balance still seems to be off, which is why if you've ever gone on a crash diet, you feel like shit constantly. You want to hurt people. You're angry.

[译文] [Dave Ricks]: 有趣的是，即使人们减了肥，那种平衡似乎仍然是失调的，这就是为什么如果你尝试过那种“速成节食（crash diet）”，你会觉得一直像一坨屎一样难受。你想伤害别人。你很愤怒。

[原文] [Dave Ricks]: And on these medicines, that doesn't happen.

[译文] [Dave Ricks]: 而用了这些药，这种情况就不会发生。

[原文] [Host]: Yes.

[译文] [Host]: 是的。

[原文] [Dave Ricks]: Which is the miracle. People feel good and lose weight.

[译文] [Dave Ricks]: 这就是奇迹所在。人们感觉良好，同时体重在下降。

章节 9：基因疗法的商业困局：SaaS模式与“一次性治愈” (The Business of Cures: SaaS vs. "One-and-Done")

📝 本节摘要：

对话转向了生物医药行业最核心的商业模式挑战：如何为“治愈”定价？主持人用软件行业作比喻，将需要长期服用的GLP-1药物比作SaaS（软件即服务），而将“一次性治愈”的基因疗法比作传统的盒装软件（Shrink-wrap software）。Dave Ricks坦承，目前的医疗支付体系完全是基于“按片计价”的，无法适应基因疗法（如礼来正在研发的PCSK9基因编辑，可终身降低LDL胆固醇）。为了打破这一僵局，Ricks提出了大胆的创新支付构想：模仿SaaS模式，实行“按效付费”的分期付款制度，甚至引入“保修（Warranty）”机制——如果疗法失效，药企需承担后果。

[原文] [Host]: If you have a medicine that is recurring and it, you know, presents some income stream for Eli Lilly, now, maybe nothing is truly recurring in the sense that, you know, all patent protection ends, but nonetheless, there's something on an ongoing basis and I guess there are various ways to extend that, then some genetic medicine comes along. It's one time.

[译文] [Host]: 如果你有一种药物是经常性（需长期服用）的，它能为Eli Lilly带来某种收入流——当然，也许没有什么是真正永远经常性的，因为专利保护总会结束，但这依然是一种持续的基础，而且我猜还有各种方法可以延长它——然后，某种基因药物出现了。它是一次性的。

[原文] [Dave Ricks]: Yep, one and done.

[译文] [Dave Ricks]: 是的，一次搞定（one and done）。

[原文] [Host]: Exactly. Is it in practice possible to charge enough upfront such that as a company looking at its portfolio—

[译文] [Host]: 没错。实际上有可能在前期收取足够的费用，使得作为一家审视自己投资组合的公司——

[原文] [Dave Ricks]: Pays back the R&D?

[译文] [Dave Ricks]: 能收回研发成本？

[原文] [Host]: Yeah, you are in fact neutral as to which it is? Because from first principles, for the patient, it's way better to do that—

[译文] [Host]: 是的，你们实际上对这两种模式持中立态度吗？因为从第一性原理来看，对患者来说，那样做（一次性治愈）要好得多——

[原文] [Dave Ricks]: I think you asked about a value perception problem, and I think we need to overcome that. We're doing that by studying and all these other conditions people recognize as conditions and then we'll insure. And because obesity is sort of this master switch to all these things, that's an achievable thing. It just costs a lot of R&D.

[译文] [Dave Ricks]: 我想你问的是关于价值认知的问题，我认为我们需要克服这一点。我们正在通过研究所有这些人们认可的疾病状况来做到这一点，然后我们会获得承保。因为肥胖在某种程度上是所有这些问题的“总开关”，所以这是一件可实现的事情。只是这需要巨额的研发投入。

[原文] [Host]: I'm talking about perception. I think he's talking about reality. Yeah, you're talking about actually pricing, which is, why is it that the industry's evolved to have a unit pricing model? It's back to like a shrinkwrap software world, right?

[译文] [Host]: 我说的是认知。我想他说的是现实。是的，你说的是实际定价的问题，也就是为什么这个行业演变成了一种“单价计费模型”？这就像回到了那个“盒装软件（shrinkwrap software）”的世界，对吧？

[原文] [Dave Ricks]: Where you're basically just shipping a box and all your value has to be captured upon that invoice.

[译文] [Dave Ricks]: 你基本上只是发一个盒子，你所有的价值都必须在那张发票上体现出来。

[原文] [Host]: Right. Yes.

[译文] [Host]: 对。是的。

[原文] [Dave Ricks]: That is how we price all medicines.

[译文] [Dave Ricks]: 这就是我们目前对所有药物的定价方式。

[原文] [Host]: You're currently, you know, in the SaaS model and, you know, tech people know that SaaS is way better than the shrinkwrap software business model.

[译文] [Host]: 你们（指GLP-1业务）目前处于SaaS模式，你知道，科技界的人都知道SaaS比盒装软件的商业模式要好得多。

[原文] [Dave Ricks]: Yes.

[译文] [Dave Ricks]: 是的。

[原文] [Host]: And genetic medicines are shrinkwrapped software.

[译文] [Host]: 而基因药物就是盒装软件。

[原文] [Dave Ricks]: Exactly.

[译文] [Dave Ricks]: 没错。

[原文] [Host]: Exactly. You know, wouldn't you be crazy to go back even though it's better for the patient?

[译文] [Host]: 没错。你知道，即使这对患者更好，如果你要退回到那种模式，岂不是疯了吗？

[原文] [Dave Ricks]: Yeah, so I think, so we have some genetic medicines coming and we're thinking actively about this. For instance, we have a medicine development that will knock down your LDL if it's safe enough in a one and done PCSK9 edit in your liver and presumably that will last the rest of your life and your LDLs will be between 20 and 40 forever. It looks like an amazing drug.

[译文] [Dave Ricks]: 是的，所以我想——我们确实有一些基因药物即将问世，我们也正在积极思考这个问题。例如，我们正在开发一种药物，如果足够安全的话，它可以通过在你肝脏中进行一次性的PCSK9基因编辑来降低你的LDL（低密度脂蛋白），据推测这将持续你的余生，你的LDL数值将永远保持在20到40之间。这看起来像是一款神奇的药物。

[原文] [Host]: Yeah.

[译文] [Host]: 是的。

[原文] [Dave Ricks]: Of course, there's problems with these delivery systems, we have to rule out safety, but let's just say it works. How would one price that? Because you're displacing a medicine that costs, I don't know, $8,000-$9,000 per year.

[译文] [Dave Ricks]: 当然，这些递送系统还存在问题，我们必须排除安全隐患，但我们就假设它有效。你要怎么给它定价？因为你正在取代一种每年花费——我不知道——大概8000到9000美元的药物。

[原文] [Host]: Right.

[译文] [Host]: 对。

[原文] [Dave Ricks]: We need to innovate that pricing model.

[译文] [Dave Ricks]: 我们需要创新那种定价模式。

[原文] [Host]: Why haven't we?

[译文] [Host]: 为什么我们还没做到？

[原文] [Dave Ricks]: It's mostly because the consumption side has no capability to do this. Particularly governments have built all, back to the regulatory incumbency problem, built all this stack of rules around the idea that I buy one unit, I pay X. Whereas here you buy one unit and we want money over time. What is that?

[译文] [Dave Ricks]: 主要是因为消费端没有能力这样做。特别是政府，又回到那个监管的“在位者问题”上，他们围绕着“我买一个单位，我付X元”的概念建立了一整套规则。而在这种情况下（基因疗法），你买了一个单位，但我们要的是随着时间推移的付款。那算什么呢？

[原文] [Dave Ricks]: But it's conceivable that one could create like a licensing concept, stealing from the SaaS model, where you say, "We'll do the procedure for free, and as long as it's working for you, you will deposit X amount in our bank account and you're getting the value and we're getting paid for our research. If it doesn't work," you know, so that invokes a warranty as well.

[译文] [Dave Ricks]: 但这是可以想象的，我们可以创建一个类似许可（licensing）的概念，偷师SaaS模式。你可以说：“我们免费为你做这个手术，只要它对你有效，你就定期向我们的银行账户存入X金额，这样你获得了价值，我们的研究也获得了回报。如果它无效，”——你知道，这就引入了保修（warranty）机制。

[原文] [Dave Ricks]: That's an interesting idea and one we're thinking about for these more common, because so far gene therapy is mostly for uncommon things where they've just charged it and someone's paid, but for common gene therapy to really be unlocked, this has to be solved.

[译文] [Dave Ricks]: 这是一个有趣的想法，也是我们正在为那些更常见的疾病考虑的方案。因为到目前为止，基因疗法主要针对罕见病，他们就是直接收费，然后有人买单了；但对于常见病的基因疗法要想真正被解锁，这个问题必须得到解决。

章节 10：全球定价悖论与“总净差额”泡沫 (The Global Pricing Paradox & The "Gross-to-Net" Bubble)

📝 本节摘要：

本节切入最具争议的药价话题。主持人指出美国实际上在通过高药价“补贴”全球的药物研发，而欧洲等单一支付体系享受了“搭便车”的红利。Dave Ricks坦承这种差异导致了严重的社会撕裂，并以胰岛素为例，揭露了美国药价虚高的核心机制——“总净差额泡沫（Gross-to-Net Bubble）”。他解释道，虽然制药公司实际到手的净价格（约40美元）多年未变，但在PBM（药品福利管理者）的“回扣竞价”机制下，标价被被人为推高至275美元。这种扭曲的体系导致中间商获得了高额回扣，而最弱势的无保险群体却被迫支付天价。

[原文] [Host]: There's the much discussed, like, maybe the top discussed topic in pharma that people know about generally is pharma pricing and the disparity between the US and internationally where, you know, all the cost is in R&D, the cost of actually producing the drugs is fairly low. And so single-payer healthcare systems internationally pay very low prices and so the R&D cost is borne by the US.

[译文] [Host]: 这里有一个被广泛讨论——甚至可能是制药行业中大众最熟知、讨论最多的话题，那就是药品定价以及美国与国际市场之间的差异。众所周知，所有的成本都在研发（R&D）上，而实际生产药物的成本相当低。因此，国际上的单一支付医疗体系支付的价格非常低，结果就是研发成本由美国承担了。

[原文] [Host]: And the biggest problem is not only, like, at the margin, maybe you have fewer drugs developed because this phenomenon because, you know, you have fewer returns. I think honestly the biggest problem is the social issues it creates in the US where it turns people against pharma and, you know, the insulin price disparities between the US and Canada and things like that.

[译文] [Host]: 最大的问题不仅仅是——比如在边际上——也许因为这种现象导致回报减少，开发出的药物变少了。老实说，我认为最大的问题是它在美国造成的社会问题，它让人们反对制药行业，比如美国和加拿大之间胰岛素价格的巨大差异这类事情。

[原文] [Dave Ricks]: Which no longer exist by the way because we fixed that, but yes.

[译文] [Dave Ricks]: 顺便说一句，这种差异已经不复存在了，因为我们解决了这个问题，但你是对的。

[原文] [Host]: But that was like the hot topic for—

[译文] [Host]: 但那曾经是热门话题，持续了——

[原文] [Dave Ricks]: Yeah, it was a hot topic.

[译文] [Dave Ricks]: 是的，那确实是个热门话题。

[原文] [Host]: For such a long time.

[译文] [Host]: 持续了很长时间。

[原文] [Dave Ricks]: And it needed to be fixed. And that's a classic example of this commercial environment I spoke about. I mean, our actual net on insulin really hasn't changed. It's like $30 or $40, but the list price got up to $275. Why? We were competing on the spread.

[译文] [Dave Ricks]: 而且它确实需要被解决。那是我之前提到的这种商业环境的一个典型例子。我的意思是，我们在胰岛素上的实际净收入（net）其实并没有改变。大概就是30或40美元，但标价（list price）却涨到了275美元。为什么？因为我们在通过“差价（spread）”进行竞争。

[原文] [Dave Ricks]: And so that just drove this huge, and so the individual—

[译文] [Dave Ricks]: 而这导致了巨大的——所以个人——

[原文] [Host]: When you say the spread, what do you mean?

[译文] [Host]: 当你说“差价”时，你是指什么？

[原文] [Dave Ricks]: Okay, so insulin, so the latest versions were launched in the '90s and 2000s, but they got quite along in their lifecycle because—

[译文] [Dave Ricks]: 好的，关于胰岛素，最新版本是在90年代和2000年代推出的，但它们的生命周期持续了相当长的时间，因为——

[原文] [Host]: As in close to the end of the—

[译文] [Host]: 意思是接近结束——

[原文] [Dave Ricks]: Well, they were past their patent window actually, but there were no competitors. Why? Beause net pricing was pretty low. How could it be so low? Well, the incumbent players, mostly Novo and Lilly, we can come back to that on GLPs as well, same players, had a lot of CapEx in the ground.

[译文] [Dave Ricks]: 嗯，实际上它们已经过了专利保护期，但却没有竞争对手。为什么？因为净价格相当低。怎么会这么低呢？因为现有的玩家，主要是Novo（诺和诺德）和Lilly（礼来）——我们在GLP药物上也可以回过头来谈这个，还是这几家——已经投入了大量的资本支出（CapEx）。

[原文] [Dave Ricks]: And to start a new insulin company made no sense at the net prices we were achieving. Yet at the same time, the public viewed this as this outrageous price gouging because list prices, if we were getting about $40 a month of therapy, were like $270.

[译文] [Dave Ricks]: 按照我们当时达到的净价格，创办一家新的胰岛素公司是毫无意义的。然而与此同时，公众却认为这是令人发指的价格欺诈，因为虽然我们每月的治疗费用只拿到大约40美元，但标价却高达270美元左右。

[原文] [Host]: And so we— So who's getting the 235?

[译文] [Host]: 所以我们——那么谁拿走了那235美元？

[原文] [Dave Ricks]: Yeah, so middle actors. And so big PBMs like UnitedHealthcare runs and CVS and Express Scripts were offering to employers and others, the government as well, "We will create an auction, and in this auction, we will get a take on the percent we save you off the list price and you'll get a lower price than you could on your own. And we will create an auction by..."

[译文] [Dave Ricks]: 是的，是中间商。那些大型PBM（药品福利管理机构），比如UnitedHealthcare运营的、CVS以及Express Scripts，它们向雇主和其他机构（包括政府）提议：“我们将创建一个拍卖，在这个拍卖中，我们会从帮你节省的标价折扣中抽取一部分，而你将获得比你自己谈更低的价格。我们将通过……来创建这个拍卖。”

[原文] [Dave Ricks]: and this is actually a highly interchangeable class. They're not exactly the same substance, but they are pretty close. And so they could do this more easily and they'll say, "We'll just pick one, and every January, manufacturer, mail us your best deal," and the best deals that tended to win, we learned through time, were those that had the biggest spread between the high list price and a low net price.

[译文] [Dave Ricks]: 这实际上是一个高度可替代的药物类别。它们并不是完全相同的物质，但非常接近。所以他们可以更容易地通过这种方式操作，他们会说：“我们只选一种，每年一月，制造商，把你们最好的报价寄给我们。”随着时间的推移我们发现，那些往往能赢的“最好报价”，是那些在高标价和低净价之间拥有最大“差价（spread）”的报价。

[原文] [Dave Ricks]: So we competed on this. What did we do? We kept raising the list price and modestly lowering our net price. That was how the market evolved. And after 10 years, you had this huge bubble, gross to net bubble, and who was paying?

[译文] [Dave Ricks]: 所以我们就为此展开了竞争。我们做了什么？我们不断提高标价，同时适度降低我们的净价。市场就是这样演变的。十年后，就形成了这个巨大的泡沫——“总净差额泡沫（gross to net bubble）”。而谁在为此买单？

[原文] [Host]: Okay, so you weren't—

[译文] [Host]: 好吧，所以你们并没有——

[原文] [Dave Ricks]: No real payers. But the person who walked in the pharmacy with no insurance, they had to pay that. That's outrageous. That's what I mean. That should not exist.

[译文] [Dave Ricks]: 不是真正的付款人（指保险公司）。而是那些走进药房却没有保险的人，他们必须支付那个价格（高标价）。这是令人发指的。这就是我的意思。这不应该存在。

章节 11：打破泡沫：自杀式降价与全球“搭便车” (Bursting the Bubble: The Insulin "Hack" & The Global Free Rider)

📝 本节摘要：

为了刺破胰岛素价格的“总净差额泡沫”，Dave Ricks采取了一项近乎“自杀式”的行动：推出自家高价药的廉价仿制版。这一举动直接威胁了中间商（PBM）的盈利模式，Ricks甚至收到了警告：“别这么做，这是对我们模式的威胁。”但他置之不理，哪怕初期没有保险公司愿意将这款低价药纳入目录。随后，话题转向了更宏大的全球博弈：美国实际上是在独自承担全球药物研发的成本。Ricks指出，在绝大多数生物科技公司的商业计划书里，80%到100%的利润预期都来自美国市场，而其他国家实际上是在“搭便车”，享受着美国消费者资助的创新成果。

[原文] [Dave Ricks]: We were able to disarm that through a number of actions. But the critical first one was we went to the government and we said, "We don't want this problem anymore. We're an innovative company"

[译文] [Dave Ricks]: 我们通过一系列行动解除了那个武装。但关键的第一步是我们去找政府说：“我们不想再要这个问题了。我们是一家创新公司。”

[原文] [Host]: 'Cause it looks bad for you.

[译文] [Host]: 因为这让你们看起来很糟糕。

[原文] [Dave Ricks]: It looks terrible. And it's also producing these unfair outcomes. We're going to, because no generic has applied for a copy of our medicine or biosimilar, we will create our own. So we launched our own biosimilar. It says Lilly on the bottle. It says Insulin Lispro, which is the generic name.

[译文] [Dave Ricks]: 看起来糟透了。而且它也造成了这些不公平的结果。（我们说）我们要——因为没有仿制药厂商申请复制我们的药或生物类似药——我们将创造我们自己的（仿制药）。所以我们推出了我们自己的生物类似药。瓶子上写着Lilly（礼来）。写着Insulin Lispro（赖脯胰岛素），这是通用名。

[原文] [Dave Ricks]: And we priced it really cheap, like a third of the regular product. Similar net price actually, but quite a bit less. Interesting fact, that launched, all these insurance companies and middle people called me and said, "Why'd you do this?"

[译文] [Dave Ricks]: 我们把价格定得很便宜，大概是常规产品的三分之一。实际上净价格差不多，但（标价）低了很多。有趣的事实是，这药一推出，所有这些保险公司和中间人都打电话给我说：“你为什么要这么做？”

[原文] [Dave Ricks]: I said, "Well, because we're trying to lower insulin prices." They said, "Don't. This is a threat to our model." It's like, "I don't care." Like, we have a higher calling. And in the first year, no formularies covered this. So it was really only for that cash payer. No insurance company picked it up even though it was dramatically cheaper.

[译文] [Dave Ricks]: 我说：“嗯，因为我们想降低胰岛素价格。”他们说：“别这么做。这是对我们模式的威胁。”我的反应是：“我不在乎。”就像是，我们有更高的使命。第一年，没有处方集（formularies）覆盖这个药。所以它真的只针对那些用现金支付的人。没有保险公司选它，尽管它便宜得多。

[原文] [Dave Ricks]: Now it's about half of the volume, but still half not, because that model of this margin spread model is still there. But we largely have defanged that problem by introducing a copy of our own medicine.

[译文] [Dave Ricks]: 现在它的销量大概占了一半，但仍有一半不是，因为那个“利润差价模式”依然存在。但通过引入我们自己药物的复制品，我们很大程度上已经拔掉了那个问题的毒牙。

[原文] [Host]: You know, I think we can get into differences between the US healthcare system and the rest of the world where the US has a very vibrant private healthcare system, but it's kind of weirdly unpopular at least in certain parts of the, you know, political discussion. But there's a choice.

[译文] [Host]: 你知道，我想我们可以深入探讨一下美国医疗体系与世界其他地区乃至全球的差异，美国拥有非常有活力的私营医疗体系，但这在某种程度上奇怪地不受欢迎，至少在某些政治讨论中是这样。但这是一种选择。

[原文] [Dave Ricks]: Yeah, so but taking about R&D. No, it's amazing. Actually let me just answer that. So it is true. If you went out and said, "Hey, I want to back some biotechs," and they sent you their business plan, 80% to 100% of the revenue and return they'll pitch you on is the US.

[译文] [Dave Ricks]: 是的，不过说到研发。不，这很惊人。实际上让我来回答这个问题。这是真的。如果你走出去说，“嘿，我想投资一些生物科技公司，”然后他们发给你商业计划书，他们向你推销的收入和回报中，80%到100%都来自美国。

[原文] [Dave Ricks]: Meaning there is no return outside the US if you start at the point of origin of the idea. Now, once we get to the market with a product, it's not sensical to not market it in these countries at whatever price you can get because your R&D is paid for on the US launch.

[译文] [Dave Ricks]: 这意味着如果你从创意的原点开始算，美国以外是没有回报的。当然，一旦我们的产品进入市场，不在这些国家以你能拿到的任何价格销售是不理智的，因为你的研发成本已经通过在美国的上市发布赚回来了。

[原文] [Dave Ricks]: So here you're just margin gathering—

[译文] [Dave Ricks]: 所以在这里你只是在收集边际利润——

[原文] [Host]: But it's the free-rider problem.

[译文] [Host]: 但这就是“搭便车问题（free-rider problem）”。

[原文] [Dave Ricks]: But it's the free-rider problem.

[译文] [Dave Ricks]: 没错，这就是“搭便车问题”。

[原文] [Host]: But to John's point, this seems increasingly politically untenable. Americans are—

[译文] [Host]: 但就John的观点来看，这在政治上似乎越来越站不住脚了。美国人正在——

[原文] [Dave Ricks]: I agree. Americans are waking up to this. We should get rid of it. It's actually not good for our industry either because you get a skewing in addition to the problem, the social problem.

[译文] [Dave Ricks]: 我同意。美国人正在觉醒。我们应该摆脱这种情况。这对我们行业其实也不好，因为除了这个问题，社会问题之外，还会导致偏差。

[原文] [Dave Ricks]: So what does everyone do? They tune the R&D model to the US healthcare problems when actually we're 5% of the world population. So shouldn't we tune it to the global health problems and reward the global health problems?

[译文] [Dave Ricks]: 那么大家都在做什么呢？他们将研发模式调整为针对美国的医疗问题，而实际上我们只占世界人口的5%。那么，难道我们不应该将其调整为针对全球健康问题，并奖励解决全球健康问题的行为吗？

章节 12：“单一公平价格”提案与1.4万美元的赤霞珠 (The "One Fair Price" Proposal & The $14,000 Cabernet)

📝 本节摘要：

针对全球药价不公与美国本土的定价乱象，Dave Ricks提出了一项名为“单一公平价格（One Fair Price）”的改革方案。该方案主张两点：第一，在国际上建立基于人均GDP的定价契约，让富裕国家承担应有的研发成本；第二，在美国国内废除所有不透明的回扣与折扣，实行“一口价”透明交易。为了说明美国现行医疗定价的荒谬性，他打了一个生动的比方：这就像在餐厅点了一瓶标价1.4万美元的红酒，侍者却告诉你“别担心，这不全是你要付的钱”，导致消费者完全失去了价格判断力。

[原文] [Host]: When you say we should get rid of it, we should solve it...

[译文] [Host]: 当你说我们应该摆脱这种状况，我们应该解决它……

[原文] [Dave Ricks]: Yeah.

[译文] [Dave Ricks]: 是的。

[原文] [Host]: How?

[译文] [Host]: 怎么做？

[原文] [Dave Ricks]: Yeah, so I pitched this idea to this administration actually, which I call the one fair price. So—

[译文] [Dave Ricks]: 是的，实际上我向本届政府推销过这个想法，我称之为“单一公平价格（one fair price）”。所以——

[原文] [Host]: Good branding.

[译文] [Host]: 名字起得不错。

[原文] [Dave Ricks]: Yeah, yeah, yeah. We're learning. I need a hat. One fair price. OFP. That's it, yeah.

[译文] [Dave Ricks]: 是的，是的，是的。我们也在学习。我需要一顶帽子。单一公平价格。OFP。就是这个，是的。

[原文] [Dave Ricks]: But the idea would be that manufacturers introduce at the price they want. They are restricted by only a couple things. One is that they will need to introduce it in other developed economies in a price band that's sensical to the GDP of those countries.

[译文] [Dave Ricks]: 这个想法的核心是，制造商可以按他们想要的价格推出产品。他们只受几件事的限制。其一是，他们需要在其他发达经济体推出该产品时，设定一个与这些国家GDP相符的合理价格区间。

[原文] [Dave Ricks]: GDP per capita. Because the ability to pay I think should largely be borne by more wealthy nations.

[译文] [Dave Ricks]: 人均GDP。因为我认为支付能力（的责任）应主要由更富裕的国家承担。

[原文] [Host]: Okay, so you're saying—

[译文] [Host]: 好的，所以你是说——

[原文] [Dave Ricks]: That's where the surplus is.

[译文] [Dave Ricks]: 那里才是（经济）盈余所在。

[原文] [Host]: You introduce a drug that costs $100 in the US. You're saying it should cost, you know, on the order of, you know, $70 in— So, say, Britain, $70 in the UK or whatever.

[译文] [Host]: 你在美国推出一种售价100美元的药。你是说它在——比如说英国，应该定价在70美元左右，或者类似的水平。

[原文] [Dave Ricks]: Yeah, it's 30% less GDP per capita, we would introduce it at 70.

[译文] [Dave Ricks]: 是的，如果他们的人均GDP低30%，我们就定价70美元。

[原文] [Dave Ricks]: Those countries can say yes or no, but we would basically sign a compact that would say, "That's our deal. We think it's worth a hundred." We can not sell it there, but not because we're lowering it below 70. We have to charge them what we think it's worth.

[译文] [Dave Ricks]: 那些国家可以说行或不行，但我们基本上会签署一份契约，声明：“这就是我们的交易。我们认为它值100。”我们可以不在那里销售，但这不能是因为我们将价格降到了70以下。我们必须向他们收取我们认为值得的价格。

[原文] [Host]: And you could do that today.

[译文] [Host]: 其实你们今天就可以这样做。

[原文] [Dave Ricks]: We could.

[译文] [Dave Ricks]: 我们是可以。

[原文] [Host]: So, you know, why not just do it? Why do you need a compact?

[译文] [Host]: 那么，你知道，为什么不直接做呢？为什么需要一份契约？

[原文] [Dave Ricks]: That's fix number one. Fix number two is that the reimbursement system in the US, starting with the US government itself, would need to get rid of all discounts and rebates so that the product moves through the channel physically at one price and is reimbursed at that same price.

[译文] [Dave Ricks]: 那是第一个修正方案。第二个修正方案是，美国的报销系统——从美国政府自身开始——需要废除所有的折扣和回扣，这样产品在渠道中实际流转时就只有一个价格，并且按同样的价格进行报销。

[原文] [Dave Ricks]: You have to select that price. And here you're not price discriminating anymore. You have to sort of look at all the equities around that and say, "This is the fair price that I select and I'm going to live with that," just like other commodities and things we buy every day. And there's no skimming of that number.

[译文] [Dave Ricks]: 你必须选择那个价格。在这里你不再进行价格歧视。你必须审视这周围所有的资产价值，然后说：“这就是我选择的公平价格，我将接受这个价格，”就像我们每天购买的其他商品和东西一样。而且没有人能从这个数字中抽成（skimming）。

[原文] [Host]: What you're describing is an instantiation of what I view as the general phenomenon. One of the biggest shortcomings of the US healthcare system in my view and one of the biggest critiques you can have is none of the numbers mean anything. Like, just a number that you see, they're all lies. And that kind of has to lead to market failure essentially.

[译文] [Host]: 你所描述的其实是我所认为的一个普遍现象的具体例证。在我看来，美国医疗体系最大的缺陷之一，也是你能提出的最大批评之一，就是所有的数字都没有任何意义。就像你看到的每一个数字，它们都是谎言。这本质上必然导致市场失灵。

[原文] [Dave Ricks]: Yeah, could you imagine this? Like, we go to a restaurant tonight and someone gives us the wine list and a bottle of like a hundred dollar Napa Cabernet is like $14,000.

[译文] [Dave Ricks]: 是的，你能想象这个场景吗？比如，我们今晚去一家餐厅，有人递给我们酒单，一瓶原本大概100美元的纳帕赤霞珠（Napa Cabernet），标价却是1.4万美元。

[原文] [Dave Ricks]: But then the waiter says, "Don't worry, that's not your copay."

[译文] [Dave Ricks]: 但接着侍者说：“别担心，那不是你要付的共付额（copay）。”

[原文] [Host]: Yeah. And so what's my copay? "I can't tell you."

[译文] [Host]: 是的。那我问：“那我的共付额是多少？”他说：“我不能告诉你。”

[原文] [Dave Ricks]: We enjoy the wine. We have a nice dinner. Four weeks later, you get a letter in the mail that starts at the top by saying, "This is not a bill," but it says the $14,000 and then there's a number of deductions. And it says, "This is not a bill. Don't pay this." And then later you get an actual bill. This is healthcare pricing.

[译文] [Dave Ricks]: 我们享用了美酒。我们吃了一顿愉快的晚餐。四周后，你收到一封邮件，开头写着：“这不是账单”，但上面写着1.4万美元，然后是一堆扣除项。它写着：“这不是账单。请勿支付。”然后过段时间你才收到真正的账单。这就是医疗定价。

章节 13：恶意合规与650美元的抽血 (Malicious Compliance & The $650 Blood Draw)

📝 本节摘要：

既然价格如此不透明，为何不强制公开？Dave Ricks直言，美国最近推行的医疗价格透明化法规是一场“彻底的失败”。医院对此采取了“恶意合规（Malicious Compliance）”的态度——他们虽然公布了数据，却将其埋藏在难以解读的乱码数据库中，就像《银河系漫游指南》里那些只有爬过“豹子窝”才能找到的文件。Ricks还分享了自己的亲身经历：他在看医生时顺便做了一次简单的抽血，结果收到了650美元的账单。这揭示了美国医疗体系的另一个荒谬之处：仅仅因为抽血是在“医院大楼”而非“门诊诊所”进行，费用就翻了几倍，而系统竟然奖励这种低效的高成本模式。

[原文] [Host]: But it feels like you could pull on this thread quite a bit and, you know, the next admin should, of just the numbers should mean something. Like, the FTC does this a lot. You know, they say that for consumers, numbers should be trusted and yet we kind of let the healthcare system off the hook.

[译文] [Host]: 但感觉你可以在这个话题上深入挖掘一下，而且下届政府也应该这么做，就是数字应该代表真实的含义。比如FTC（联邦贸易委员会）经常这样做。他们说对于消费者而言，数字应该是可信的，然而我们却某种程度上放过了医疗系统。

[原文] [Dave Ricks]: Yeah, there's no pre posting of pricing. Now, with drugs, there is. So one of the things we get criticism, I push back, is, like, "Well, because you can know a list price of a drug." Actually most every, the other 90%, you mostly can't know the price.

[译文] [Dave Ricks]: 是的，没有预先公布的价格。现在，药品是有（标价）的。所以当我们受到批评时，我会反驳说：“嗯，至少你能知道药品的标价。”实际上绝大多数——其他的90%（医疗服务）——你基本上无法知道价格。

[原文] [Host]: Well, we've introduced regulations in the last couple of years mandating some degree of transparency here for healthcare.

[译文] [Host]: 嗯，我们在过去几年引入了法规，强制要求医疗保健领域在一定程度上实现透明化。

[原文] [Dave Ricks]: Yes. Total failure.

[译文] [Dave Ricks]: 是的。彻底的失败（Total failure）。

[原文] [Host]: Have those worked?

[译文] [Host]:那些起作用了吗？

[原文] [Dave Ricks]: Yeah. Look up in your region who has actually complied. Compliance is terrible. Most major hospital systems have not complied. Or if they have, they put on a website somewhere a coded database that is impossible to interpret with ICD-10 codes and price points that consumers cannot digest. It's like "The Hitchhiker's Guide to the Galaxy."

[译文] [Dave Ricks]: 是的。你去查查你所在地区谁真正合规了。合规情况糟糕透顶。大多数主要医院系统都没有合规。或者即使他们做了，也只是在网站某个角落放一个编码数据库，里面全是普通消费者无法理解的ICD-10代码和价格点。这简直就像《银河系漫游指南》（里的情节）。

[原文] [Host]: It's a non-searchable— Beware of the Leopard.

[译文] [Host]: 是不可搜索的——“当心豹子（Beware of the Leopard）”。（注：梗出自《银河系漫游指南》，讽刺文件被藏在极难找到的地方）

[原文] [Dave Ricks]: You know, file, flat file, with everything they have. That doesn't work. It's malicious compliance.

[译文] [Dave Ricks]: 你知道，就是那种文件，扁平文件，堆砌了他们所有的东西。那根本没用。那是恶意合规（malicious compliance）。

[原文] [Host]: Yeah, or facial or whatever. And so that's not working and we need to have that.

[译文] [Host]: 是的，或者是表面功夫之类的。所以那行不通，我们需要真正的透明。

[原文] [Dave Ricks]: I've actually gone to like an imaging center and I asked, like, "What's this cost?" And the person gets irritated with me. Like, "Why are you asking that?" I'm like, "I don't know." Like...

[译文] [Dave Ricks]: 我实际上去过像影像中心这样的地方，我问：“这个多少钱？”那个人对我感到很恼火。好像在说：“你为什么要问这个？”我就像：“我不知道啊。”就像……

[原文] [Host]: I generally ask that before I consume things.

[译文] [Host]: 我通常在消费之前都会问这个问题。

[原文] [Dave Ricks]: I want to know what it costs. I had a situation, my physician is like attached to a hospital. Here's another terrible thing about US healthcare is that the federal rules require payment differences based on site of care.

[译文] [Dave Ricks]: 我想知道它多少钱。我遇到过一种情况，我的医生是隶属于一家医院的。这是美国医疗保健另一件可怕的事情：联邦规则要求根据“护理地点（site of care）”支付不同的费用。

[原文] [Dave Ricks]: So if you're an outpatient clinic, which is theoretically cheaper, the reimbursement is lower, not because it's less valuable, but because it's cheaper to deliver. We punish that. We reward where it's more expensive in a hospital complex.

[译文] [Dave Ricks]: 所以如果你是一家门诊诊所，理论上成本更低，报销额度就更低——不是因为它的价值更低，而是因为它的交付成本更低。我们惩罚这种（高效）。而在更昂贵的医院综合体里，我们却给予奖励。

[原文] [Dave Ricks]: So my doctor's there, he's like, "Hey, you can get a blood draw downstairs. Why don't you go do that now and then come back up?" So I went down there, they drew my blood. Five minutes later, I went to his office, the result was there, and I'm like, "Oh, I should have asked what that costs."

[译文] [Dave Ricks]: 所以我的医生在那儿（医院里），他说：“嘿，你可以在楼下抽个血。你为什么不现在去做了然后再上来？”所以我下去了，他们抽了我的血。五分钟后，我回到他的办公室，结果已经在那里了，我想，“噢，我应该问问那个多少钱的。”

[原文] [Dave Ricks]: So on my way out, I asked. They're like, "That was $650." I'm like, "For a blood draw? Like, that's insane." And they ran it in their own lab there. No one asks.

[译文] [Dave Ricks]: 所以在出去的路上，我问了。他们说：“那是650美元。”我说：“就为了一个抽血？这太疯狂了。”而且他们就是在自己的实验室里跑的数据。从来没人问过。

[原文] [Dave Ricks]: And I think that's a major, major pricing problem we have in healthcare. And then, you know, I think people are insulated from those costs, but in strange ways. Some things are deductible, some are not. And so it's really very difficult to make informed consumer economic decisions in health and we need to improve that.

[译文] [Dave Ricks]: 我认为这是我们在医疗保健中面临的一个重大的、重大的定价问题。而且，你知道，我认为人们与这些成本是隔绝的，是以一种奇怪的方式。有些东西可以抵扣，有些不行。所以要在健康方面做出明智的消费者经济决策真的非常困难，我们需要改进这一点。

章节 14：橡木地板诊所与“奇怪”的私营医疗 (Oak-Floored Clinics & The "Weird" Private Healthcare)

📝 本节摘要：

话题转向了对美国私营医疗体系的文化审视。作为同样在爱尔兰长大的背景，主持人指出美国医疗虽然拥有极短的等待时间和强大的诊断能力（如美国和中国占据了全球70%的诊断产能），但其“营利性”本质和无处不在的药物广告常让外人感到震惊。Dave Ricks对比了他在加拿大生活的经历，指出美国医疗竞争往往走偏了方向——初级诊所竞相铺设“橡木地板”和豪华装饰来吸引患者，而非比拼基础服务效率。此外，他深刻指出现有的医疗筹资模式是为“急性护理”设计的，已完全不适应如今以慢性病和预防为主的健康需求。

[原文] [Host]: The other thing I observe about the US healthcare system, so Patrick and I both grew up in Ireland, moved here for college, and the US has a very vibrant private healthcare system, which is different from kind of many other countries which have, you know, public government-run and funded healthcare systems.

[译文] [Host]: 我观察到美国医疗体系的另一件事是——Patrick和我都主要是在爱尔兰长大的，后来搬到这里上大学——美国拥有一个非常有活力的私营医疗体系，这与许多其他拥有公共政府运营和资助医疗体系的国家截然不同。

[原文] [Host]: And what I notice is people just have a weird reaction to private healthcare. Private hospitals people think are weird despite the fact that, you know, you have much shorter wait times in the US than you have in many other countries because we have more kind of hospitals and all these new private outpatient kind of specialty clinics.

[译文] [Host]: 我注意到人们对私营医疗有一种奇怪的反应。人们觉得私立医院很奇怪，尽管事实是，你在美国的等待时间比在许多其他国家要短得多，因为我们有更多类型的医院以及所有这些新的私营门诊专科诊所。

[原文] [Host]: But the biggest one is when people come to the US, they're shocked by pharma advertising. And, you know, they put on a sports game and just, like, the break comes and it's all pharma ads.

[译文] [Host]: 但最大的冲击是当人们来到美国时，他们对医药广告感到震惊。你知道，他们打开电视看体育比赛，一到广告休息时间，全是医药广告。

[原文] [Host]: And my understanding is that there's, again, a significant pro-social defense of this, which is many of these drugs are shown through all the extensive trials that, you know, we make you guys do to have a significant health benefit, and then it leads to them being prescribed more by doctors because people actually ask their doctors, they do in fact do the thing, they ask their doctor about them, and it leads to more usage.

[译文] [Host]: 我的理解是，这同样有一个重要的亲社会（pro-social）辩护理由，那就是许多此类药物通过了所有广泛的试验——你知道，我们要求你们做的那些——证明具有显著的健康益处，然后这导致医生更多地开具这些处方，因为人们实际上会问他们的医生，他们确实会这么做，他们向医生询问这些药，从而导致了更多的使用。

[原文] [Host]: But yet people just find the whole thing weird. You know, private, for-profit healthcare. And so do you have a view on where this goes? What we can do about it?

[译文] [Host]: 但人们还是觉得整件事很奇怪。你知道，私营的、营利性的医疗保健。所以你对这会如何发展有什么看法吗？我们能做些什么？

[原文] [Dave Ricks]: Yeah. Well, not having grown up in a system like Ireland, but I lived in Canada for a while, for six years, so I was treated in that and I've seen it, yeah, I find it weird the other way. Totally. Because that's your conditioning.

[译文] [Dave Ricks]: 是的。嗯，虽然我不是在像爱尔兰那样的系统中长大的，但我曾在加拿大生活过一段时间，六年，我在那里接受过治疗，我也见过那种系统。是的，反过来我也觉得那种系统很奇怪。完全如此。因为那是你的习惯使然。

[原文] [Dave Ricks]: I think there's good and bad to both. I think actually, we were talking about prevention earlier, to some degree primary care, what I experienced in that country was pretty good quality of care, very standardized, which has a confidence boosting thing when it's the same for everybody.

[译文] [Dave Ricks]: 我认为两者各有利弊。实际上，我们之前谈到了预防，在某种程度上的初级护理，我在那个国家（加拿大）体验到的是相当不错的护理质量，非常标准化，当所有人得到的待遇都一样时，这会有一种增强信心的作用。

[原文] [Dave Ricks]: That also, in specialty care, is implemented but actually to kind of a negative result, because take, like, diagnostics. The US and China have something like 70% of all diagnostic capacity in the world. That's crazy.

[译文] [Dave Ricks]: 这在专科护理中也有实施，但实际上结果却有些消极，因为拿诊断来说。美国和中国拥有全世界大约70%的诊断产能。这太疯狂了。

[原文] [Host]: Yeah.

[译文] [Host]: 是的。

[原文] [Dave Ricks]: But your chance of finding a tumor or something is much, much higher in those two countries than Ireland or certainly the UK. And that's not a good outcome. Why? Because I think they're focused on cost of delivery and evenness instead of exceptional care.

[译文] [Dave Ricks]: 但在这两个国家发现肿瘤或其他疾病的几率要比爱尔兰或当然还有英国高得多得多。那（指英爱的情况）并不是一个好结果。为什么？因为我认为他们关注的是交付成本和平均主义，而不是卓越的护理。

[原文] [Dave Ricks]: So I think we've moved on that axis of, like, let's offer something that could be the best and charge for it, yet for common conditions, we've also moved on that axis unnecessarily. And so here you end up with hard, you know, oak-floored primary care offices and beautiful drapery and furniture.

[译文] [Dave Ricks]: 所以我认为我们（美国）在这个轴向上走的是“让我们提供最好的服务并为此收费”，然而对于常见病症，我们也毫无必要地在这个轴向上移动了。所以在这里，你最终会看到那种硬木——你知道，铺着橡木地板的初级护理诊所，还有漂亮的窗帘和家具。

[原文] [Dave Ricks]: That's the basis of competition instead of actually, it's quite a simple thing, "You need your flu vaccine. Like, just get in and get out."

[译文] [Dave Ricks]: 那成了竞争的基础，而不是实际上非常简单的事情，比如“你需要流感疫苗。那就进去打完赶紧出来。”

[原文] [Dave Ricks]: And there's a third thing coming, which you touched on, which is prevention and self-care. And I actually think that if we think of the funding mechanism in our country, but also in Europe, and Europe's system has problems going forward, it was really built on an acute care model when most illness and death was accidents, you know, things we couldn't solve.

[译文] [Dave Ricks]: 还有第三件事正在发生，你也提到了，那就是预防和自我护理。实际上我认为，如果我们考虑我们国家的筹资机制，还有欧洲的——欧洲的系统未来也有问题——它实际上是建立在一个“急性护理模型”之上的，那时大多数疾病和死亡是事故，或者是我们无法解决的事情。

[原文] [Dave Ricks]: It was basically treat them as best you can and people were going to expire. That's what a hospital did. We've, of course, now evolved well beyond that. I think that's 30% of US cost. Now 70% is primary care and sort of, you know, the chronic disease.

[译文] [Dave Ricks]: 基本上就是尽力治疗，然后人就会离世。这就是以前医院做的事。当然，我们现在已经进化得远超那个阶段了。我认为那只占美国成本的30%。现在70%是初级护理以及，你知道，慢性病。

[原文] [Dave Ricks]: And those institutions and those funding models are really poorly suited to that, and particularly so if behaviors have an input into that. Don't we want people before they get the disease to modify their behavior?

[译文] [Dave Ricks]: 而那些机构和筹资模式真的非常不适合这种情况，特别是如果行为对疾病有影响的话。难道我们不想让人们在得病之前修正他们的行为吗？

[原文] [Dave Ricks]: Well, how do you charge for that? And so, you know, there's a little bit of a selection problem that, you know, the best healthcare systems get the worst behaved people because the coverage is better.

[译文] [Dave Ricks]: 可是，你怎么为此收费呢？所以，你知道，这有点像是一个选择性问题（selection problem）：最好的医疗系统吸引了行为最糟糕的人，因为覆盖范围更好。

[原文] [Dave Ricks]: So I think it is time for a rethink of the whole thing. And I would think of those three different things and try to solve for them differently. Right now, we pretty much have one answer, and the Europe answer has produced kind of an institutional rationing model that seems very fair but actually produces poor outcomes for acute conditions.

[译文] [Dave Ricks]: 所以我认为是时候重新思考整件事了。我会考虑这三件不同的事情，并尝试用不同的方式解决它们。目前，我们基本上只有一个答案，欧洲的答案产生了一种制度化的配给模型，看起来很公平，但在急性病症上实际上产生了糟糕的结果。

[原文] [Dave Ricks]: And the US, which is very expensive, also is unfair but produces good outcomes for acute conditions. Probably just the same for everything else, but costs too much. That's I think needs to be addressed.

[译文] [Dave Ricks]: 而美国，非常昂贵，也不公平，但在急性病症上产生了好的结果。除此之外的其他方面可能差不多，但成本太高了。我认为这是需要解决的问题。

章节 15：治疗指数的非线性扩张与“去中介化”未来 (Non-Linear Expansion of Therapeutic Index & The Disintermediated Future)

📝 本节摘要：

Dave Ricks在本节引入了一个核心药理学概念——“治疗指数（Therapeutic Index）”，即有效剂量与有害剂量之间的安全区间。他指出，随着RNA干扰等新技术的出现，这一指数正在呈“非线性扩张”，使得药物变得极度安全且长效（例如一年只需注射两次的Lp(a)胆固醇药物）。这种极高的安全性带来了一个革命性的推论：我们可能不再需要复杂的医疗体系来管理这些药物。Ricks以LillyDirect为例，指出患者宁愿直接掏信用卡自费，也不愿面对那些写着“这不是账单”的保险文书，这种“去中介化”的直销模式正是未来的方向。

[原文] [Dave Ricks]: In the future, and here, medicines plus information I think can play a really big role in disease prevention. In the past, we haven't been able to make... the age old problem in medicine is this thing we call therapeutic index. That's the difference between a dose which is harmful and one which is helpful.

[译文] [Dave Ricks]: 在未来，在这里，我认为“药物加信息”可以在疾病预防中发挥真正的巨大作用。在过去，我们无法做到……医学界的一个古老难题是我们称之为“治疗指数（therapeutic index）”的东西。那就是有害剂量与有益剂量之间的差值。

[原文] [Dave Ricks]: And a therapeutic index that's small is difficult. You have to very precisely dose and people have differences, so it requires a lot of attention. But over time, the techniques we make drugs with, that therapeutic index, the TI we call it, is expanding and expanding non-linearly. Because of that—

[译文] [Dave Ricks]: 治疗指数如果很小，就很困难。你必须非常精确地给药，而且人与人之间存在差异，所以这需要大量的关注。但随着时间的推移，我们制造药物的技术让那个治疗指数——我们称之为TI——正在扩张，并且是非线性地扩张。正因为如此——

[原文] [Host]: Sorry, why is it expanding?

[译文] [Host]: 抱歉，为什么它在扩张？

[原文] [Dave Ricks]: Yeah, because of new drug technologies. Two main ones. One is, going to the root of disease, whether it be genetic or RNA blocking medicine. So a lot of diseases have excess protein. We can now really pristinely block RNA production of the protein and the disease, without a lot of side effects, goes away.

[译文] [Dave Ricks]: 是的，因为新的药物技术。主要有两个。一个是直击疾病的根源，无论是基因药物还是RNA阻断药物。很多疾病都是由于蛋白质过量引起的。我们现在可以真正纯净地（pristinely）阻断该蛋白质的RNA生成，疾病就会消失，而且没有太多副作用。

[原文] [Dave Ricks]: And by the way, these medicines happily also have sort of this catalytic effect. So they last a really long time. I mentioned Lp earlier. So that's a kind of cholesterol that's untreatable today. We're developing a medicine that will be a once or twice a year treatment for this and the side effects look totally benign.

[译文] [Dave Ricks]: 顺便说一句，令人高兴的是，这些药物还具有某种催化效应。所以它们持续的时间非常长。我之前提到了Lp（脂蛋白a）。那是目前无法治疗的一种胆固醇。我们正在开发一种药物，每年只需治疗一次或两次，而且副作用看起来完全是良性的。

[原文] [Dave Ricks]: That's a really wide therapeutic index, right? So now when you have that, you can think, "Well, my trials I can run faster because I don't have worries about treatment. They can be cheaper. I can charge less and get it to more people at scale. And I actually don't really need a healthcare system."

[译文] [Dave Ricks]: 那是一个非常宽的治疗指数，对吧？所以当你拥有这个时，你会想，“嗯，我的试验可以跑得更快，因为我不担心治疗风险。它们可以更便宜。我可以收更少的钱，并规模化地提供给更多人。而且我实际上并不真的需要一个医疗体系。”

[原文] [Dave Ricks]: And here, maybe back to the GLP-1s, that's giving us a little bit of glimpse of these. These are more invasive than what I just described, but pretty safe. People know how to treat themselves. You certainly know if you have overweight or obesity. You don't need a doctor to tell you that.

[译文] [Dave Ricks]: 在这里，也许回到GLP-1药物上，这让我们对这些未来有了一点瞥见。虽然它们比我刚才描述的（基因/RNA药物）更具侵入性，但也相当安全。人们知道如何治疗自己。你肯定知道自己是否超重或肥胖。你不需要医生来告诉你这个。

[原文] [Dave Ricks]: And platforms like our direct platform have really taken off because it's self-paid, but people skip all this other morass and getting the, "This is not a bill," piece of paper. They're just like, "Here's my visa card number. Yeah, charge me 500 bucks, but my problem's getting solved."

[译文] [Dave Ricks]: 像我们这种直销平台之所以真正腾飞，是因为它是自费的，人们跳过了所有其他的泥潭，也不用去收那张写着“这不是账单”的纸。他们只是说：“这是我的Visa卡号。是的，收我500块，但我的问题解决了。”

[原文] [Dave Ricks]: I think for prevention, that's an intriguing future, direct to consumer.

[译文] [Dave Ricks]: 我认为对于预防医学来说，直接面向消费者（DTC），那是一个迷人的未来。

章节 16：谁在驱动创新？生物科技 vs. 传统的“垂直整合” (Who Drives Innovation? Biotech vs. Traditional "Vertical Integration")

📝 本节摘要：

访谈地点位于被称为“生物科技诞生地”的南旧金山，主持人借此抛出了行业格局的宏大问题：如今2/3的新药似乎都源自生物科技初创公司（Biotech），而非传统大药企（Pharma）。大药企的未来角色是否仅仅是充当“私募股权投资组合经理（PE Portfolio Manager）”，负责收购并扩大规模？Dave Ricks反驳了这种二元对立，提出了礼来的“混合模式（Hybrid Model）”。他提出了一个核心洞察：临床试验具有显著的规模经济效应（大药企做得更快、更便宜），但发明创造却具有“规模不经济（Diseconomies of Scale）”。为了解决这一矛盾，礼来采用了“分布式实验室”策略，例如在圣地亚哥建立仅有400人的独立中心，让他们像创业公司一样灵活运作，却无需为融资分心。

[原文] [Host]: We're here in the great city of South San Francisco, the home of Genentech and to some significant extent of the US biotech sector. And we're talking a whole bunch here in this conversation about fostering and inducing and creating adequate incentives for R&D.

[译文] [Host]: 我们现在位于伟大的南旧金山市，这里是Genentech（基因泰克）的故乡，在很大程度上也是美国生物科技行业的重镇。我们在这次谈话中已经谈了很多关于培育、引导和为研发创造足够激励机制的话题。

[原文] [Host]: I think the, I mean, to some extent, you can bucket biotech and pharma separately. Obviously the lines blur, but, you know, there's kind of two poles. And I think it's very striking the extent to which, as far as I can see at least, the introduction of new medicines, you know, new molecular entities, whatever, is increasingly dominated by biotechs.

[译文] [Host]: 我认为——我的意思是，在某种程度上，你可以把生物科技（Biotech）和制药公司（Pharma）分开归类。显然界限是模糊的，但也就是有两个极点。而且我认为非常引人注目的是——至少据我所见——新药的推出，也就是新分子实体（new molecular entities）之类的，正日益被生物科技公司所主导。

[原文] [Host]: And you would know the numbers better than me, but I think that around two thirds, both of the revenue and also of the, just by count, the introductions themselves, are attributable to biotechs rather than to pharma. And so I guess I'm just curious how you think about this landscape.

[译文] [Host]: 你对这些数字肯定比我更清楚，但我认为大约三分之二——无论是从收入还是仅仅从数量上来看——新药的推出都归功于生物科技公司，而不是制药公司。所以我很好奇你是如何看待这一格局的。

[原文] [Host]: I mean, maybe there's some view where the role of, in an extreme, one role of pharma would be to be a kind of private equity portfolio manager where you take stock of the landscape and you look at who's doing well, whose approach you believe in, et cetera, and you have the risky innovation be done by earlier stage entities, by venture capitalists, what have you, and then you bet on winners, you go and scale them, and you distribute them. One model.

[译文] [Host]: 我的意思是，也许有一种观点认为，在极端情况下，制药公司的一个角色可能是成为某种“私募股权投资组合经理（Private Equity Portfolio Manager）”，你去审视整个格局，看谁做得好，你相信谁的方法等等；你让那些早期实体、风险投资家去做高风险的创新，然后你押注赢家，去扩大他们的规模，并进行分销。这是一种模式。

[原文] [Host]: Traditional model is actually, no, you have all these internal R&D capabilities and you're vertically integrated and you have economies of scale and so on and so forth. Are we shifting there? You know, where between those poles ought we be? How is it changing? Just thoughts on that whole landscape?

[译文] [Host]: 传统模式实际上是——不，你拥有所有这些内部研发能力，你是垂直整合的，你拥有规模经济等等。我们正在向那边转移吗？你知道，我们应该处于这两个极点之间的什么位置？它是如何变化的？对整个格局有什么看法？

[原文] [Dave Ricks]: Yeah, well, I think there's three models that have emerged. One is the biotech that grows up. Another is the outsourced early model you're describing where we just say, "We're good at clinical trials. Everything before that, just gobble it up as companies mature." You know, because the capital market is so terrible as I described, it's a liquidity event for the investors. They go back and try something earlier.

[译文] [Dave Ricks]: 是的，嗯，我认为出现了三种模式。一种是长大了的生物科技公司。另一种就是你描述的那种早期外包模式，即我们说：“我们擅长临床试验。在那之前的所有事情，就在公司成熟时把它们吞并掉。”你知道，因为正如我所描述的，资本市场如此糟糕，这对投资者来说是一个流动性事件（套现机会）。他们会回去尝试更早期的事情。

[原文] [Dave Ricks]: And then sort of the hybrid of fully integrated plus. I don't think anyone's really pursuing just fully integrated anymore. I think your head's in the sand if you're doing that. We're running the third one.

[译文] [Dave Ricks]: 然后是某种“完全整合加（fully integrated plus）”的混合模式。我认为现在没有人真的只追求完全整合模式了。如果你那样做，我觉得你是在把头埋在沙子里。我们正在运行的是第三种（混合模式）。

[原文] [Dave Ricks]: The other two are reliable—

[译文] [Dave Ricks]: 另外两种也是可靠的——

[原文] [Host]: That hybrid?

[译文] [Host]: 那种混合模式？

[原文] [Dave Ricks]: Yeah. And why do we make that choice? I think we observe a few things. First of all, while it's true that the origin of, I think it's a little more than half of medicines approved in the last 10 years have come from biotech, hardly any of those traveled all the way through biotech because there are, as we talked about earlier, huge checks to write and risks to take and the biotech investor base is not interested in those risks, those very binary large checks.

[译文] [Dave Ricks]: 是的。我们为什么做出这个选择？我想我们观察到了几件事。首先，虽然确实——我认为过去10年批准的药物中有一半多一点源自生物科技公司——但几乎没有哪个是完全在生物科技公司内部走完全程的。因为正如我们之前谈到的，需要开出巨额支票并承担巨大风险，而生物科技投资者群体对这些风险、那些非常二元（非成即败）的大额支票并不感兴趣。

[原文] [Dave Ricks]: Whereas we can absorb them, we can run a portfolio across many of those. There's also scale economies in clinical trials. There is no doubt in my mind we are faster, more robust, probably cheaper than actually every biotech out there trying to do their own early phase clinical trials and manufacturing and distribution globally. So those things benefit scale.

[译文] [Dave Ricks]: 而我们可以吸收这些风险，我们可以在许多项目上运行一个投资组合。此外，临床试验也存在规模经济。我毫无疑问地认为，比起那些试图自己做早期临床试验、制造和全球分销的生物科技公司，我们更快、更稳健，甚至可能更便宜。所以这些事情受益于规模。

[原文] [Host]: What doesn't?

[译文] [Host]: 什么不受益于规模？

[原文] [Dave Ricks]: It is discovery. It's the early phase. I think that's a more diffuse undertaking. What we've done, starting with my predecessor maybe 15 years ago, is we started putting diverse, spreading out our labs. Scale's bad.

[译文] [Dave Ricks]: 是发现（Discovery）。是早期阶段。我认为那是一项更分散的任务。我们所做的——从我的前任大约15年前开始——是我们开始建立多样化的、分散的实验室。规模（对发现来说）是坏事。

[原文] [Host]: And I think our idea was 300 or 400 people, about right, Allow for some deviation. As in you think the—

[译文] [Host]: 我想我们的想法是300或400人，大概刚刚好，允许一些偏差。也就是说你认为——

[原文] [Dave Ricks]: Put some outposts out there. The act of invention has diseconomies of scale.

[译文] [Dave Ricks]: 在外面设立一些前哨站。发明创造的行为具有“规模不经济（diseconomies of scale）”。

[原文] [Dave Ricks]: Yeah, so we started in San Diego. We built a monoclonal antibody biotech hub there. It's produced like a third of the medicines we've made since we started. Hugely successful. There's 400 employees.

[译文] [Dave Ricks]: 是的，所以我们从圣地亚哥开始。我们在那里建立了一个单克隆抗体生物科技中心。自我们开始以来，它生产了我们所制造药物的三分之一。极其成功。那里有400名员工。

[原文] [Dave Ricks]: So it's like a biotech, but it has some benefits. They don't have to spend any time with venture capitalists or raising money or fussing over CapEx and, you know, ups and downs in the markets.

[译文] [Dave Ricks]: 所以它就像一家生物科技公司，但它有一些优势。他们不需要花任何时间去见风险投资家、筹集资金，或者为资本支出（CapEx）以及市场的起起落落而烦恼。

章节 17：中国阴影与生物科技的“安全警钟” (The "Shadow" of China & The Biotech Security Alarm)

📝 本节摘要：

谈话转向了生物医药产业的地缘政治格局。主持人指出，虽然电子制造业早已转移至亚洲，但软件业仍主要留在了美国。然而，生物科技领域正出现惊人的变化：十年前中国在全球药物管线中的份额仅为个位数，如今已逼近30%。Dave Ricks对此敲响了“警钟”。他认为，生物制药是“知识经济的超级联赛”，代表了最高端的人才与经济价值，美国绝不能拱手让人。更关键的是国家安全——他以COVID-19为例，当时80%的有效疫苗和药物由美国生产；如果局势反转，美国陷入依赖别国救命药的“被勒索境地”，后果将不堪设想。

[原文] [Host]: So we just mentioned we're in South San Francisco in the Bay Area. The Bay Area, of course, used to have a vibrant electronics manufacturing industry and—

[译文] [Host]: 我们刚才提到我们身处湾区的南旧金山。当然，湾区曾经拥有一个充满活力的电子制造业，而且——

[原文] [Dave Ricks]: Yep, it left.

[译文] [Dave Ricks]: 是的，它离开了。

[原文] [Host]: Yeah, companies like— There's still the APX sign.

[译文] [Host]: 是的，像那些公司——那里还留着Ampex（注：此处原文可能指旧招牌）的标志。

[原文] [Dave Ricks]: Yeah, exactly. And, you know, some of the old—

[译文] [Dave Ricks]: 是的，没错。而且，你知道，一些老的——

[原文] [Host]: Yes, but— Fairchild.

[译文] [Host]: 是的，但是——比如Fairchild（仙童半导体）。

[原文] [Dave Ricks]: Exactly.

[译文] [Dave Ricks]: 没错。

[原文] [Host]: But you mention, you know, Cypress Semiconductor and, you know, people don't really know what you're talking about these days. The biotech sector started here in the '70s, I guess.

[译文] [Host]: 但如果你提到Cypress Semiconductor（赛普拉斯半导体），现在的人真的不知道你在说什么了。生物科技行业大概是70年代在这里起步的。

[原文] [Dave Ricks]: Yeah, give or take.

[译文] [Dave Ricks]: 是的，差不多。

[原文] [Host]: And is, exactly, and is still today reasonably vibrant. Although, to your point, it's had a tough maybe couple of years. The share of the global drug pipeline that was Chinese 10 years ago was I think in the small single digits.

[译文] [Host]: 没错，而且直到今天它仍然相当有活力。虽然就像你说的，过去几年可能比较艰难。我认为10年前，中国在全球药物研发管线中的份额还只是个位数的一小部分。

[原文] [Dave Ricks]: Approaching zero.

[译文] [Dave Ricks]: 接近于零。

[原文] [Host]: Yeah, exactly. Right. And now I think it's high 20s, approaching a third.

[译文] [Host]: 是的，没错。对。而现在我认为是20%多，接近三分之一。

[原文] [Dave Ricks]: A third. It's 30%.

[译文] [Dave Ricks]: 三分之一。是30%。

[原文] [Host]: Okay. It's amazing. Now is in fact 30%. Where does this go? And is there a US biotech sector in 20 years? Or like electronics manufacturing, does the whole thing just go to China?

[译文] [Host]: 好的。这太惊人了。现在实际上是30%。这会向何处发展？20年后美国还会有生物科技行业吗？还是像电子制造业一样，整个行业都跑到中国去？

[原文] [Dave Ricks]: I wouldn't predict that outcome, but I think we should ring the alarm bell right now.

[译文] [Dave Ricks]: 我不会预言那种结果，但我认为我们现在就应该敲响警钟。

[原文] [Host]: Well, I mean, is it bad?

[译文] [Host]: 嗯，我的意思是，这（转移到中国）是坏事吗？

[原文] [Dave Ricks]: It's not great, I would say, I think for two reasons. One—

[译文] [Dave Ricks]: 我想说这不太好，我认为有两个原因。第一——

[原文] [Host]: But if they can do it better and faster and cheaper and we get the drugs, isn't that awesome?

[译文] [Host]: 但如果他们能做得更好、更快、更便宜，而我们能得到药物，这难道不是很棒吗？

[原文] [Dave Ricks]: That is good, especially if the last part's true. But I think the economy around biopharma I think has some unique properties that should make us want to own it. One is it is in the knowledge economy. To me is sort of the pinnacle—

[译文] [Dave Ricks]: 那是很好，尤其是如果最后那部分（指我们能得到药物）是真的话。但我认为围绕生物制药的经济具有一些独特的属性，这应该让我们想要将它掌握在自己手中。第一，它属于知识经济。对我来说，它算是某种顶峰——

[原文] [Host]: Paradigmatic knowledge economy.

[译文] [Host]: 典范式的知识经济。

[原文] [Dave Ricks]: It's the premier league of knowledge economy. You guys fund and know people... I mean, the diversity of skill sets needed to do it well at the highest level of their game is extreme. I don't think it exists, maybe rocketry, maybe there's a few other things like this, but it requires a lot of talent.

[译文] [Dave Ricks]: 它是知识经济的“超级联赛（premier league）”。你们投资并了解人才……我的意思是，要在最高水平上做好这件事，所需的技能多样性是极端的。我认为没有其他行业是这样的——也许火箭技术算一个，也许还有少数几个类似的东西——但这需要大量的人才。

[原文] [Dave Ricks]: So it tells you how you're doing I think in a way. Can you integrate these, can you train people, attract them from abroad, like you folks, or train them here and put them together in a way that produces new value?

[译文] [Dave Ricks]: 所以某种程度上，这也反映了你的国家表现如何。你能整合这些资源吗？你能培训人才、从国外吸引人才（像你们这样），或者在本土培养他们，并将他们组合在一起创造新价值吗？

[原文] [Host]: Okay, so there's a kind of shadow passing over the country if biotech—

[译文] [Host]: 好的，所以如果生物科技流失，就像有一种阴影笼罩在国家上空——

[原文] [Dave Ricks]: And it's rewarded. I mean, these are well-paying jobs. There's a big economic footprint that goes with that. And increasingly we're putting manufacturing near it, so it actually has a trickle down that's pretty significant as well.

[译文] [Dave Ricks]: 而且这是有回报的。我的意思是，这些都是高薪工作。随之而来的是巨大的经济足迹。而且我们越来越多地将制造业通过它（研发）附近安置，所以实际上也有相当显著的涓滴效应（trickle down）。

[原文] [Dave Ricks]: And then it invokes also security concerns. And you can imagine if we had the COVID pandemic, in that case, basically 80% of the medicines and vaccines that worked were produced in the United States. China produced some of those things. None of them really worked. We didn't import them.

[译文] [Dave Ricks]: 其次，这引发了安全担忧。你可以想象一下，如果我们经历了COVID疫情，在那次情况下，基本上80%奏效的药物和疫苗都是在美国生产的。中国也生产了一些东西。但没一个真正管用的。我们也没有进口它们。

[原文] [Dave Ricks]: But imagine if that was flipped. And we're in—

[译文] [Dave Ricks]: 但想象一下如果情况反转了。而我们处于——

[原文] [Host]: I mean, the EU saw this with all the battles, yeah. An extorted position.

[译文] [Host]: 我的意思是，欧盟在所有的争夺战中已经看到了这一点，是的。处于一种被勒索的境地（extorted position）。

[原文] [Dave Ricks]: Yeah, the EU had a huge controversy, and they're friendly and we had open trading, but they have had a reckoning as well. And there's some things you just want to have a national competency in.

[译文] [Dave Ricks]: 是的，欧盟经历了巨大的争议，而且他们还是盟友，我们之间有开放贸易，但他们也经历了清算和反思。有些东西你就是希望拥有“国家核心竞争力（national competency）”。

[原文] [Dave Ricks]: So, anyway, I have a theory about the industry. I think there are truly novel concepts that require a little more time and work and it is yet to be seen whether China has perfected that in a way where they can create their own local system.

[译文] [Dave Ricks]: 所以，不管怎样，我对这个行业有一个理论。我认为有些真正新颖的概念需要更多的时间和功夫，目前还有待观察中国是否已经完善了这一点，能够建立他们自己的本土系统。

[原文] [Dave Ricks]: What they've certainly shown now, though, is the iterative derivative, which is a big part of the substrate of the industry, they are refining and becoming experts in very, very quickly.

[译文] [Dave Ricks]: 不过，他们现在肯定已经展示出的是“迭代衍生物（iterative derivative）”的能力——这是该行业基础的很大一部分——他们正在改进并在这一领域非常、非常快地成为专家。

[原文] [Dave Ricks]: I think that's not all bad. There'll be more competition. You know, there's an effect in China where their own sort of price competition defeats their own industries, and you're kind of seeing that in biotech as well, the race to the bottom on pricing.

[译文] [Dave Ricks]: 我觉得这也不全是坏事。会有更多的竞争。你知道，中国有一种效应，他们自己的那种价格竞争会击败他们自己的产业，你在生物科技领域也能看到这种情况，就是价格上的“逐底竞争（race to the bottom）”。

[原文] [Dave Ricks]: But I think we want a national competency here. And I think this has been a hub. Boston is still a big hub. We want to keep those.

[译文] [Dave Ricks]: 但我认为我们需要在这里保留国家核心竞争力。这里（湾区）一直是一个中心。波士顿仍然是一个大中心。我们想要保住这些。

章节 18：专利系统的漏洞与“影子仿制”产业 (The Loophole in Patents & The "Shadow Generic" Industry)

📝 本节摘要：

在这一章节，讨论触及了生物医药创新的灰色地带。主持人指出了中国生物科技领域出现的一种新现象：大量“克隆”分子涌现，它们在专利层面上做了微小的改动以规避侵权，但药效几乎完全一致。Dave Ricks不仅承认这种“改进与复制（Refine and Replicate）”的能力，更直指美国自身专利制度的变革（从“先发明制”转向“先申请制”）是这一问题的推手。他解释道，专利本质上是公开“配方”以换取垄断权，但在AI辅助下，竞争对手能轻易计算出只有一两个原子差异的新结构，从而创造出一个合法的“影子仿制产业”，彻底破坏了原创新药的回报机制。为此，他提出了“双重保险（Belt and Suspenders）”的解决方案：给予小分子药物12年的数据独占期。

[原文] [Host]: But there's this new phenomenon where, my understanding, please correct me, is that, you know, traditionally you develop a molecule, you patent the molecule. Now there's the growth of these clones where you can have the molecule be trivially different enough for patent purposes, but still the same action and there's a huge amount of that coming out of the Chinese biotech sector. Doesn't that—

[译文] [Host]: 但现在出现了一种新现象——这是我的理解，请纠正我——传统上你开发一个分子，然后给这个分子申请专利。现在这种“克隆体（clones）”在增长，即你可以让分子在专利层面上只有微不足道的差异，但仍然具有相同的作用，而且中国生物科技领域涌现出了大量这类东西。这难道不——

[原文] [Dave Ricks]: But I think also some real, like, I mean that seems real and good and novel—

[译文] [Dave Ricks]: 但我认为也有一些真正的——我是说，那看起来也是真实的、好的且新颖的——

[原文] [Host]: Also real innovation. That's an interesting one, yeah. But don't the clones effectively erode the patent system and, you know, we would think shortening the patent life to 15 years would be bad, and/or 10 years. And this is shortening the patent life effectively.

[译文] [Host]: 也有真正的创新。这是个有趣的现象，是的。但是这些克隆体难道不是在有效地侵蚀专利制度吗？你知道，我们认为将专利寿命缩短到15年或10年是件坏事。但这（克隆现象）实际上就是在缩短专利寿命。

[原文] [Dave Ricks]: Yeah, I think that practice is what I'm talking about with this sort of refine and replicate and our own patent system forces this, right? So we have a, in 2011, the US changed the patent system to first to file versus first to invent.

[译文] [Dave Ricks]: 是的，我认为这种做法就是我所说的“改进与复制（refine and replicate）”，而我们自己的专利制度迫使这种情况发生，对吧？我们在2011年，美国将专利制度从“先发明制（first to invent）”改为了“先申请制（first to file）”。

[原文] [Dave Ricks]: You used to be able to invent and sit on your patent and all you had to do is prove, it was messy court cases 'cause your lab notebook said, "Oh, it was October of 2017 and mine says 2018. Well, which was what," right? But now you rush to file.

[译文] [Dave Ricks]: 以前你可以发明了东西然后把专利压在手里，你所要做的就是证明——那会引发混乱的官司，因为你的实验笔记写着“噢，那是2017年10月”，而我的写着2018年。好吧，到底是谁先发明的？对吧？但现在你必须争分夺秒去申请。

[原文] [Dave Ricks]: And the government I think has 12 months that they sit on that inspection and then the patent, what is a patent? It's a degree to publish your finding, right? To make it a public good in return for that monopoly.

[译文] [Dave Ricks]: 政府大概有12个月的审查期，然后专利——什么是专利？它实际上是一个公开你发现的协议，对吧？让它成为公共产品，以换取那种垄断权。

[原文] [Dave Ricks]: But if the monopoly is debased by 30 Chinese biotechs who feed that patent into a computer, the computer then can imagine chemical structures that have one or two atom differences that don't fit within the patent, and then make that substance, test it, works just the same, you've created basically a shadow generic industry and undermined the patent system itself.

[译文] [Dave Ricks]: 但是，如果这种垄断权被30家中国生物科技公司贬值了——他们把那个专利输入电脑，电脑就能构想出只有一两个原子差异、不在专利覆盖范围内的化学结构，然后制造出这种物质，测试它，效果完全一样——那你基本上就是创造了一个“影子仿制药产业（shadow generic industry）”，并破坏了专利制度本身。

[原文] [Host]: So was the shadow generic industry basically launched by first to file because we published the instruction manuals?

[译文] [Host]: 所以说，这个“影子仿制药产业”基本上是由“先申请制”催生的，因为我们主动公布了说明书？

[原文] [Dave Ricks]: Yeah.

[译文] [Dave Ricks]: 是的。

[原文] [Host]: I hadn't realized that. And do you think, is it your view if you just switch back?

[译文] [Host]: 我以前没意识到这一点。那么你认为，如果只是切回旧制度能行吗？

[原文] [Dave Ricks]: No, what I would do is, if we want a sort of like an America-first patent system, or Europe first, we should do two things. We should create a belt and suspenders so that, some patents are tricky to write.

[译文] [Dave Ricks]: 不，我会做的是——如果我们想要一个类似“美国优先”或“欧洲优先”的专利系统——我们应该做两件事。我们应该建立一种“双重保险（belt and suspenders，字面意为皮带加背带）”，因为有些专利很难写。

[原文] [Dave Ricks]: So a belt and suspenders would be, say, independent of a patent, we'll give you 12 years if you produce primary data on this product all the way through phase III. That's a $3 billion ticket. These copycats aren't going to do it. They're certainly not going to do it in US data.

[译文] [Dave Ricks]: 所谓“双重保险”就是说，独立于专利之外，如果你能提供这个产品贯穿至三期临床的原始数据，我们就给你12年的保护期。那是一张价值30亿美元的入场券。那些模仿者是不会去做的。他们肯定不会用美国的数据来做这件事。

[原文] [Dave Ricks]: And that'll be more or less constrained in markets that don't care about that issue and don't have this data exclusivity provision. This already exists in biologics by the way, so all we have to do is, in small molecules, and this problem we're talking about is mostly a small molecule problem.

[译文] [Dave Ricks]: 这样他们就或多或少会被限制在那些不关心这个问题、也没有这种数据独占条款的市场里。顺便说一句，这在生物大分子药物（biologics）中已经存在了，所以我们要做的就是把它应用到小分子药物上，因为我们谈论的这个问题主要是一个小分子问题。

章节 19：离岸制造与“5%规则”的隐患 (Offshore Chemistry & The "5% Rule" Risk)

📝 本节摘要：

仿制药虽然为社会提供了极其廉价的药物（如每天仅需3美分的百忧解），但其背后的质量隐患却鲜为人知。Dave Ricks揭示了仿制药与原研药并非“完全一样”的科学真相：根据“5%规则”，仿制药的有效成分允许有正负5%的偏差，且其使用的赋形剂（Excipients）可能影响药物吸收率。更令人担忧的是，受限于环保法规（EPA）和成本压力，绝大多数化学制药厂已转移至印度和中国。Ricks警告说，这种过度依赖离岸制造的供应链极其脆弱，美国应该为“供应链韧性”支付溢价，而不是一味追求低价。

[原文] [Host]: I don't know when exactly the generics industry, like, really rose to be such a large share of consumed pharmaceuticals today, but I'm very curious about the quality control and the attendant regulatory apparatus around it where, I mean, as we've been discussing, there's such scrupulous and stringency around clinical trials for new molecules and introductions and so forth.

[译文] [Host]: 我不知道仿制药行业确切是从什么时候开始真正崛起，占据了今天药品消费的如此大份额，但我对它的质量控制以及随之而来的监管机制非常好奇。我的意思是，正如我们一直讨论的，对于新分子的临床试验和引入等等，有着如此严谨和严苛的要求。

[原文] [Host]: My understanding is that for generics, a lot of the external validation certification happens at the manufacturing plant level, not at the individual drug level. And that for the individual drugs, it is substantially a case of self-certification and, you know, presentation of one's own data as opposed to external audits.

[译文] [Host]: 我的理解是，对于仿制药，很多外部验证认证是发生在制造工厂层面的，而不是针对单个药物层面的。而且对于单个药物，这在很大程度上属于自我认证，即提交自己的数据，而不是接受外部审计。

[原文] [Host]: And there have been many cases of documented fraud and malfeasance here. The largest generic manufacturer in India, I forget its name, paid a half a billion dollar fine in 2013 for—

[译文] [Host]: 这里有很多有记录的欺诈和渎职案件。印度最大的仿制药制造商——我忘了名字了——在2013年支付了5亿美元的罚款，因为——

[原文] [Dave Ricks]: Yeah, Cipla.

[译文] [Dave Ricks]: 是的，Cipla（西普拉）。

[原文] [Host]: Yeah, for rampant fraud and falsification, abuse of the biosimilarity analysis and so forth, which obviously is bad, but, like, the apparatus and the FDA regime is such that there are very obvious incentives for that to happen.

[译文] [Host]: 是的，因为猖獗的欺诈和伪造、滥用生物等效性分析等等。这显然很糟糕，但是，这种机制和FDA的制度本身就存在非常明显的诱因，促使这种事情发生。

[原文] [Host]: And then I'm very struck by how anecdotally and online, there are so many reports of people switching from brand name medication to generic medication, finding them to be very different, you know, subjectively and experientially, switching back to the branded pharmaceutical, and, you know, things going back to normal as it were.

[译文] [Host]: 然后我非常震惊的是，在坊间传闻和网络上，有太多关于人们从品牌药换成仿制药后，发现它们非常不同——你知道，在主观和体验上——然后又换回品牌药，事情就“恢复正常”了的报告。

[原文] [Host]: And so there's some some kind of subjective version of, you know, the generic is, in fact, not, you know, directly substitutable. And so I guess, I mean, I know nothing about this domain. This is all just observed from afar. I guess I'm curious for your thoughts here. Like, does the generic industry actually work as well as we think it does? How much fraud is there in actuality?

[译文] [Host]: 所以这就存在某种主观版本的看法，即仿制药事实上并不能直接替代。我猜——我是说，我对这个领域一无所知，这都是从远处观察到的——我很好奇你的想法。比如，仿制药行业真的像我们认为的那样有效吗？实际上有多少欺诈行为？

[原文] [Dave Ricks]: I think on the whole, the generic environment in the US, which is the most developed in the sense of percent of medicines consumed and the cheapest in the OECD, has been largely a positive outcome because it's made effective medicines abundant at very, very low cost.

[译文] [Dave Ricks]: 我认为总的来说，美国的仿制药环境——就药品消费百分比而言是最发达的，在经合组织（OECD）国家中也是最便宜的——在很大程度上是一个积极的成果，因为它让有效的药物以非常非常低的成本变得丰富。

[原文] [Dave Ricks]: That said, and I say that because, you know, take an invention like statins or HIV drugs or we invented Prozac, still the standard of care in treating depression, it's like three cents a day. I don't know any product you can buy for three cents a day, but, you know, that's an incredible value for the system.

[译文] [Dave Ricks]: 话虽如此——我之所以这么说，是因为拿他汀类药物或艾滋病药物，或者我们发明的Prozac（百忧解）来说，它仍然是治疗抑郁症的标准疗法，现在的价格大概是每天3美分。我不知道你还能买到什么每天只要3美分的产品，但这为系统提供了不可思议的价值。

[原文] [Dave Ricks]: There's two deviations that can occur. One is, it's the so-called 5% rule where plus or minus 5% of the active ingredient and some dosages in some people are more sensitive than that and I think some of those people have an effect.

[译文] [Dave Ricks]: （仿制药）可能会出现两种偏差。一种是所谓的“5%规则”，即有效成分允许有正负5%的偏差，而有些人在某些剂量下比这个范围更敏感，我认为其中一些人会受到影响。

[原文] [Dave Ricks]: Also, there's this, particularly in a dry product, in a pill, there's excipients, which are the other ingredients. Most of what you're taking is not actually the active ingredient. Some of them are buffering compounds, some of them affect absorption rate. So those two things combined do lead to different effects.

[译文] [Dave Ricks]: 此外还有这个——特别是在干制剂中，在药丸里——有赋形剂（excipients），就是其他的成分。你吃下去的大部分东西其实不是有效成分。其中一些是缓冲化合物，一些影响吸收率。所以这两件事结合起来确实会导致不同的效果。

[原文] [Dave Ricks]: And there is no requirement for small molecule chemical medicine to show proof of efficacy of any kind. So you can do pretty simple laboratory experiments and absorption experiments in a small number of people.

[译文] [Dave Ricks]: 而且，对于小分子化学药物，没有任何要求需要出示任何形式的疗效证明。所以你只需要在少数人身上做相当简单的实验室实验和吸收实验即可。

[原文] [Dave Ricks]: I think the manufacturing problems you mentioned are real. In the quest for low cost, it all moved offshore. These are basically chemical plants and in the prior iteration of that technology and our EPA, it became non-economic to make these medicines in the US or Ireland for that matter.

[译文] [Dave Ricks]: 我认为你提到的制造问题是真实存在的。为了追求低成本，制造业全都转移到了海外。这些基本上就是化工厂，在上一代技术和我们的EPA（环保署）规定下，在美国——或者爱尔兰——制造这些药物变得不划算了。

[原文] [Dave Ricks]: There are some eastern European companies, there's a big Israeli company, there's several Indian companies, and many Chinese companies that are in this business. That's where these drugs come from. I think that is not so stable either. And we probably should pay a little bit more for generics.

[译文] [Dave Ricks]: 有一些东欧公司，有一家大型以色列公司，有几家印度公司，还有许多中国公司从事这一业务。这就是这些药物的来源。我认为这也不太稳定。我们可能应该为仿制药多付一点钱。

[原文] [Dave Ricks]: You sometimes read about injectable generics in particular that run short. That's a more complicated manufacturing process, so if you do it cheaply, you run into more problems. We probably should pay a little premium for resilience. Right now, that's not the situation.

[译文] [Dave Ricks]: 你有时会读到特别是注射类仿制药出现短缺。那是一个更复杂的制造过程，所以如果你为了便宜而做，就会遇到更多问题。我们可能应该为“韧性（resilience）”支付一点溢价。但目前情况并非如此。

章节 20：希拉毒蜥与“肠促胰素”的魔法 (Gila Monsters & The "Incretin Effect")

📝 本节摘要：

GLP-1药物如今被视为减肥神药，但其背后的科学远不止于此。Dave Ricks追溯了这段历史：从1971年发现“肠促胰素效应”（即肠道能指挥大脑和胰腺处理食物），到在希拉毒蜥（Gila Monster）的唾液中发现一种能模拟人类GLP-1但半衰期更长的蛋白质。Ricks解释了礼来如何通过蛋白质工程将这种原本在体内只能存活5分钟的激素，改造成一周只需注射一次的超级药物（如Tirzepatide）。更令人兴奋的是，这种药物的作用范围正在惊人地扩大：除了减重和糖尿病，它还能显著降低炎症指标（CRP），甚至在早期观察中显示出抑制烟酒瘾等成瘾行为的潜力。

[原文] [Host]: So GLPs obviously were initially researched, the initial R&D was done for diabetes.

[译文] [Host]: 显然GLP类药物最初是被研究用于——最初的研发是针对糖尿病的。

[原文] [Dave Ricks]: Yes.

[译文] [Dave Ricks]: 是的。

[原文] [Host]: And then it was noticed during the clinical trials that people were losing weight.

[译文] [Host]: 然后在临床试验期间注意到人们体重减轻了。

[原文] [Dave Ricks]: So first of all, it's different from what you just described as this accident because actually we knew and we were involved with the, we launched the first GLP-1 in the world.

[译文] [Dave Ricks]: 首先，这和你刚才描述的那种“意外”不同，因为实际上我们早就知道，而且我们参与其中——我们推出了世界上第一款GLP-1药物。

[原文] [Dave Ricks]: So GLP-1, let's go all the way back, it's a super family of things we call incretins. These are hormones that signal our brain and other tissues from our gut. We always think about our brain being in charge. That's not how we work. And it's back to this basic system of survival, which is nutrition.

[译文] [Dave Ricks]: 那么GLP-1，让我们回溯一下，它属于我们称为“肠促胰素（incretins）”的一个超家族。这些是从我们的肠道向大脑和其他组织发出信号的激素。我们总是认为是大脑在掌管一切。但我们的运作方式并非如此。这回到了生存的基本系统，即营养。

[原文] [Dave Ricks]: When you eat a meal, which hopefully we'll do later, our gut actually communicates with the rest of the body, "Hey, food's on board. You don't have to eat as much." Maybe you get a satiation signal. Your fat cells are told to absorb free fatty acids. Your liver kicks into gear to release glycogen and other things.

[译文] [Dave Ricks]: 当你吃一顿饭时——希望我们待会儿也能吃上一顿——我们的肠道实际上会与其身体其他部分沟通：“嘿，食物来了。你不必再吃那么多了。”也许你会收到一个饱腹感信号。你的脂肪细胞被告知吸收游离脂肪酸。你的肝脏开始运转释放糖原和其他东西。

[原文] [Dave Ricks]: So all that process is, insulin is released to absorb the nutrients, is kicked off by incretins. This was discovered in 1971 basically, called the incretin effect.

[译文] [Dave Ricks]: 所以整个过程——胰岛素被释放以吸收营养——是由肠促胰素启动的。这基本上是在1971年被发现的，被称为“肠促胰素效应（incretin effect）”。

[原文] [Dave Ricks]: The problem with these hormones is our own versions have a half-life of like five minutes. So they don't make very good drugs. If you take that protein and sequence it, people did this, you'd have to walk around with an infusion all day. So the longer-lasting action was the invention.

[译文] [Dave Ricks]: 这些激素的问题在于，我们人体自身的版本半衰期只有大约五分钟。所以它们做不成很好的药物。如果你提取那种蛋白质并进行测序——人们确实这么做过——你就得整天挂着输液袋走来走去。所以，长效作用才是真正的发明。

[原文] [Dave Ricks]: And the first one that was, before we really knew how to do protein engineering systematically, which we can do now, it was found in nature actually, famously, in the saliva of a Gila monster.

[译文] [Dave Ricks]: 而第一个（长效药物），在我们真正知道如何系统地进行蛋白质工程之前（现在我们会了），实际上是在自然界中发现的——非常出名——是在希拉毒蜥（Gila monster）的唾液中。

[原文] [Dave Ricks]: So randomly some zoologist was testing the interesting properties of Gila monsters and noticed, and profiled all these proteins, and one of them was a mimetic of human GLP-1. Another scientist found that paper and said, "That's interesting. Let's test that compound," a few different amino acids, and sure enough, it lasted about four hours half-life.

[译文] [Dave Ricks]: 某个动物学家随机测试希拉毒蜥的有趣特性时注意到了这一点，并对所有这些蛋白质进行了分析，其中一种是人类GLP-1的模拟物。另一位科学家发现了那篇论文并说：“这很有趣。让我们测试一下那种化合物。”只有几个氨基酸不同，果不其然，它的半衰期大约是四小时。

[原文] [Dave Ricks]: So we can make it a twice a day injection. We made that into a medicine for diabetes. And on the cover of our annual report in 2006, there's a woman who was one of the first patients with a quote, says, "My diabetes is under control and my friends say I'm losing a little weight." That was 2006.

[译文] [Dave Ricks]: 所以我们可以把它制成一天注射两次的药物。我们把它做成了治疗糖尿病的药。在我们在2006年的年度报告封面上，有一位最早期的患者，她有一句引言说：“我的糖尿病得到了控制，而且我的朋友们说我瘦了一点。”那是2006年。

[原文] [Dave Ricks]: Why didn't we do it then? Well, we needed to get the dosages higher. And it turns out that this mechanism, which is common for a lot of hormones, has a threshold effect for efficacy. You have to get above a certain level in your blood, and certainly to lose weight and really suppress appetite, have to get that number up, but a peak-to-trough effect on side effects.

[译文] [Dave Ricks]: 为什么我们当时没做（减肥药）？嗯，我们需要提高剂量。事实证明，这种机制（这在许多激素中很常见）具有疗效的阈值效应。你必须让血液中的浓度超过一定水平，特别是为了减肥和真正抑制食欲，必须把那个数字提上去，但由于峰谷效应（peak-to-trough effect），又会产生副作用。

[原文] [Dave Ricks]: So the up-down part causes the nausea, but the absolute level causes the effect. So how do you separate those things? You need a flat long-acting.

[译文] [Dave Ricks]: 这种上上下下的波动会导致恶心，但绝对水平决定了疗效。那么你如何将这两者分开呢？你需要一种平稳的长效药物。

[原文] [Dave Ricks]: So we made a once a week GLP-1 called dulaglutide. We stuck the protein, the native sequence, to the backbone of basically a monoclonal antibody to extend its life. Novo Nordisk did a similar thing. That became semaglutide and Ozempic. And then we put the original two hormones together, GIP/GLP, in tirzepatide, which is better than those in terms of weight loss.

[译文] [Dave Ricks]: 所以我们制造了一种每周一次的GLP-1，叫度拉糖肽（dulaglutide）。我们将蛋白质——天然序列——粘附在基本上是单克隆抗体的骨架上，以延长其寿命。诺和诺德（Novo Nordisk）也做了类似的事情，那就成了索马鲁肽（semaglutide）和Ozempic。然后我们将最初的两种激素GIP和GLP结合在一起，制成了替尔泊肽（tirzepatide），它在减肥方面比那些都要好。

[原文] [Dave Ricks]: But inflammation markers drop precipitously early. There's a marker called CRP, C-reactive protein, which is a marker for heart attack risk. In weeks, that starts to drop, really like 60%-70%. Why is that happening? It's dislocated from the drug effect.

[译文] [Dave Ricks]: 但炎症标志物在早期就急剧下降。有一种标志物叫CRP，C反应蛋白，它是心脏病发作风险的标志物。在几周内，它就开始下降，真的下降了60%到70%。为什么会发生这种情况？这与药物（减重）效应是错开的。

[原文] [Dave Ricks]: So clearly these drugs go to the brain and they signal the brain. That signal gets translated into downregulating dopamine and the desire for dopamine. And so like cigarette smoking drops precipitously. And opioid use disorder will test, alcohol drops precipitously. Shopping, everything.

[译文] [Dave Ricks]: 显然这些药物进入了大脑并向大脑发出信号。那个信号被转化为下调多巴胺以及对多巴胺的渴望。所以像吸烟这样的行为急剧减少。我们还将测试阿片类药物使用障碍，酒精摄入也急剧下降。购物、所有这些事情（成瘾行为）也是如此。

章节 21：口服药的必然未来与广告的“必要之恶” (The Inevitable Oral Future & The "Necessary Evil" of Ads)

📝 本节摘要：

尽管GLP-1药物正如日中天，Dave Ricks却冷静地指出，目前美国仅有约1200万人使用，相对于1亿的潜在患者群体（甚至全球数亿人）来说，这仅仅是冰山一角。他揭示了一个严峻的制造瓶颈：现有的注射剂生产极其复杂，即便拼命建造“超级工厂”也难以满足全球需求。因此，礼来的战略重心必须转向口服制剂（如Orforglipron），因为只有片剂才能实现数十亿剂量的工业化量产。此外，针对备受诟病的医药广告，Ricks给出了基于数据的辩护：如果没有推广，一项医疗发明平均需要16年才能被广泛采用；而广告能将这一时间缩短至4-8年，让救命药更快触达患者。

[原文] [Host]: What fraction of the population, let's say the population over 35, will be on a GLP-1 in 15 years?

[译文] [Host]: 15年后，大概会有多大比例的人口——比如说35岁以上的人口——会使用GLP-1药物？

[原文] [Dave Ricks]: Well, today in the US, we probably have 10 million people, maybe 12, if we include the compounded market, the non-approved drugs. But it's really a fraction of the adult population, and even if you just take obesity, it should be a hundred million. We have a long, long way to go.

[译文] [Dave Ricks]: 嗯，今天在美国，我们大概有1000万人，如果算上复方药市场（非批准药物），可能有1200万。但这真的只是成年人口的一小部分，即使只算肥胖症，潜在人群也应该有一个亿。我们还有很长很长的路要走。

[原文] [Dave Ricks]: Actually, the number one prescribed form of these medications is Zepbound self-buy. We sell more than that than our insured business.

[译文] [Dave Ricks]: 实际上，这类药物开出最多的形式是Zepbound的自费购买（self-buy）。我们这部分的销量比我们保险覆盖的业务还要多。

[原文] [Dave Ricks]: The oral project I mentioned is a key part of that because we've literally already made billions of doses and we are capacity constrained in some sense on the injectable systems.

[译文] [Dave Ricks]: 我提到的口服药项目是其中的关键部分，因为我们实际上已经制造了数十亿剂（口服药），而在注射系统上，我们在某种意义上受到产能限制。

[原文] [Dave Ricks]: Unfortunately, there's not a good learning curve left. We've sort of built the scaled plants. We just have to build more of them. We've built six or seven of these mega plants that produce hundreds of millions of these injection systems and we're only treating 10 or 12 million Americans, maybe 20, 30 globally.

[译文] [Dave Ricks]: 不幸的是，（注射剂）已经没有太好的学习曲线红利了。我们已经建立了规模化的工厂。我们只能建更多这样的工厂。我们已经建了六七个这样的“超级工厂”，生产数亿套这种注射系统，但我们也只能治疗1000万到1200万美国人，全球可能也就是2000万到3000万。

[原文] [Dave Ricks]: So to get to half a billion people globally, that's not the path. The orals have to work. We can't keep stamping out these. It'll take too long.

[译文] [Dave Ricks]: 所以要想覆盖全球5亿人，（注射剂）这条路走不通。口服药必须成功。我们不能一直靠这种（注射剂生产线）硬压，那太慢了。

[原文] [Dave Ricks]: The orals have to work, they have to be approved. They're not going to be as good as these multi-acting injectable hormones, but we can probably stratify people. If you need to lose a lot of weight, okay, start there. And maintenance with the oral is going to be a key segment.

[译文] [Dave Ricks]: 口服药必须奏效，必须获得批准。它们的效果可能不如这些多重作用的注射激素那么好，但我们可以对人群进行分层。如果你需要减掉大量体重，好吧，从注射开始。然后用口服药进行维持治疗，这将是一个关键的细分市场。

[原文] [Host]: Well, you asked about consumer advertising and I think actually, people hate the commercial part of our business. I never watch TV except when I'm traveling... and I'm like, "Are you kidding me? Like, how many ads are we running, and everyone else?"

[译文] [Dave Ricks]: 嗯，你问到了消费者广告，我认为实际上人们讨厌我们业务中的商业部分。我除了旅行时从不看电视……（看到广告时）我会想：“开玩笑吧？我们到底在播多少广告？还有其他人的？”

[原文] [Dave Ricks]: Still you do it. Why do you do it? Because it works. Like, it's still a productive spend. But also promotion to physicians, which consumers don't see, is a big part of what we do.

[译文] [Dave Ricks]: 但你还是做了。为什么要做？因为它有效。这仍然是一笔有产出的支出。不过，针对医生的推广——这是消费者看不到的——也是我们工作的一大部分。

[原文] [Dave Ricks]: Mostly if left to their own, and there's been studies on this of medical inventions that are not promoted. Yeah, they won't actually be adopted. It's about a 16-year path to full adoption.

[译文] [Dave Ricks]: 如果任其自然——关于没有被推广的医疗发明有过相关研究——是的，它们实际上不会被采用。完全普及大约需要16年的时间。

[原文] [Dave Ricks]: With the medicine promoted, it's half that. We have an internal goal to halve that again, to get to four years to full, whatever it is, get to it on a global scale. I think it's ambitious but serves a purpose.

[译文] [Dave Ricks]: 如果进行了药物推广，这个时间会减半（约8年）。我们还有一个内部目标，就是再减半，争取在4年内实现全球范围的全面普及。我认为这很有野心，但确实有其意义。

章节 22：灰色地带的“中国多肽”与LillyDirect的诞生 (The Grey Market of "Chinese Peptides" & The Birth of LillyDirect)

📝 本节摘要：

针对硅谷兴起的“生物黑客”风潮，Dave Ricks严厉警告了使用未获批“中国多肽（Chinese peptides）”或复方药物的风险。他指出，这些标有“非供人类使用”的白色粉末不仅涉及严重的知识产权盗窃，更可能导致肾衰竭等永久性损伤。随后，对话转向了礼来的反击之举——LillyDirect。Ricks透露，这个直销平台诞生于胰岛素价格战的硝烟中，当初是为了对抗那些拒绝上架低价胰岛素的中间商（PBM）。如今，这已演变成一项数十亿美元的业务，礼来正像Adobe销售软件一样，绕过寻租的中间环节，直接向患者销售减肥药。

[原文] [Host]: But my understanding is the avant-garde Silicon Valley denizens, you know, the frontier is really in Chinese peptides.

[译文] [Host]: 但我的理解是，那些前卫的硅谷居民，你知道，他们的前沿阵地实际上是在“中国多肽（Chinese peptides）”上。

[原文] [Dave Ricks]: Yeah, frightening. So here we're getting into the compounding. So, of course, there's probably always been a segment of society that was comfortable using unapproved things.

[译文] [Dave Ricks]: 是的，这很可怕。这就把我们带入了“复方药物（compounding）”的话题。当然，社会上可能一直有一部分人习惯于使用未经批准的东西。

[原文] [Dave Ricks]: What is a Chinese peptide? It's an unapproved medicine that's never been tested in man and is made in a Chinese lab. It might be what you say. This is basically the same source for the tirzepatide compounded that people get.

[译文] [Dave Ricks]: 什么是“中国多肽”？它是一种未经批准的药物，从未在人体上进行过测试，是在中国实验室制造的。它可能就是你说的那种东西。这基本上也是人们获得的复方替尔泊肽（tirzepatide）的来源。

[原文] [Dave Ricks]: People buy that from things that look like legitimate companies, some are publicly traded even, that formulate them and are violating our patent.

[译文] [Dave Ricks]: 人们从那些看起来合法的公司那里购买——有些甚至是上市公司——这些公司配制这些药物，实际上是在侵犯我们的专利。

[原文] [Dave Ricks]: My problem with those companies is less about trying to, I like the fact that people could shortcut the pain in the butt of the healthcare system and go direct and we see the phenomena of what the internet's done to commerce could apply to health. I think that's net a good thing. What I don't like is they're stealing my IP.

[译文] [Dave Ricks]: 我对这些公司的问题不在于——我其实喜欢人们可以抄近道，避开医疗体系的麻烦，直接购买，我们看到互联网对商业的影响也可以应用于健康领域。我认为这总体上是件好事。我不喜欢的是他们在偷窃我的知识产权（IP）。

[原文] [Dave Ricks]: They say, "Oh, we're not following that rule. We're following a different rule, which is customization." All these patients who need tirzepatide, even though you can buy six different dosage forms, they need a dose in between these six, or, oh, the efficacy is boosted by vitamin XYZ.

[译文] [Dave Ricks]: 他们说：“噢，我们不适用那条规则。我们适用的是另一条规则，即‘定制化（customization）’。”（好像）所有这些需要替尔泊肽的患者，即使可以买到六种不同的剂型，他们偏偏需要这六种之间的剂量；或者说，噢，加上维生素XYZ疗效会增强。

[原文] [Dave Ricks]: And then you have the folks you're talking about who are served by an industry started when I think steroids became a big deal and the bodybuilding craze. They're all based in like Long Beach these places. And it's like Peptides USA, which is the opposite of what it is, right? It's Chinese peptides.

[译文] [Dave Ricks]: 还有你提到的那群人，他们是由一个伴随类固醇和健美热潮兴起的产业服务的。这些公司都设在像长滩（Long Beach）这样的地方。名字叫什么“美国多肽（Peptides USA）”，实际上完全相反，对吧？那是中国多肽。

[原文] [Dave Ricks]: And they'll sell things to you that say, "Not for human use." Literally, that's how they protect themselves legally. And you're injecting, you're putting saline in and you're putting this white powder in your body that says, "Not for human use." Really a terrible idea.

[译文] [Dave Ricks]: 他们卖给你的东西上写着“非供人类使用（Not for human use）”。字面上就是这样，这是他们在法律上保护自己的方式。而你却在注射它，你把生理盐水注入这种标着“非供人类使用”的白色粉末里，然后打进自己身体。这真是个糟糕透顶的主意。

[原文] [Dave Ricks]: And it's not going to end well. And there are people who've had chronic kidney failure and permanent liver damage.

[译文] [Dave Ricks]: 这不会有好结果的。已经有人因此患上了慢性肾衰竭和永久性肝损伤。

[原文] [Host]: You're here in South San Francisco, the headquarters of not only, or, you know, the place of Genentech, but also payments innovation. And so you—

[译文] [Host]: 你现在在南旧金山，这里不仅是基因泰克的总部所在地，也是支付创新的重镇。所以你——

[原文] [Dave Ricks]: Yes, here we are. We're working together on the Eli Direct stuff.

[译文] [Dave Ricks]: 是的，我们在这儿。我们正在LillyDirect项目上合作。

[原文] [Dave Ricks]: Yeah, I mean, talk about accidental experiments. So this came out, back to the insulin story... One of the fights we were having was with a large PBM company that also owns a pharmacy chain. And we were worried that they actually, a different pharmacy chain actually threatened not to carry our low-price insulin 'cause they couldn't make enough money on it.

[译文] [Dave Ricks]: 是的，说起意外的实验。这要追溯到胰岛素的故事……我们当时正与一家拥有连锁药店的大型PBM公司进行斗争。我们当时很担心，实际上另一家连锁药店威胁说不卖我们的低价胰岛素，因为他们在上面赚不到足够的钱。

[原文] [Dave Ricks]: So I just looked at him and said, "This is what this was for, this idea that's been on the shelf. We cannot be beholden to this. We have to have a route to market ourselves," which we had not had since the company was founded as a pharmacy.

[译文] [Dave Ricks]: 于是我看着他说：“这就是这个（LillyDirect）计划存在的意义，这个一直被搁置的想法。我们不能受制于人。我们必须拥有一条自己的上市渠道。”这是自公司作为一家药房成立以来，我们就未曾拥有过的。

[原文] [Dave Ricks]: Then we launched Zepbound and we said, "Ah, this feels like the killer app for a direct-to-patient experience because the diagnosis step is dead easy." Everybody knows, everyone knows the biomarker tool in their bathroom. It's called the scale.

[译文] [Dave Ricks]: 然后我们推出了Zepbound，我们说：“啊，这感觉像是直接面向患者（DTC）体验的‘杀手级应用（killer app）’，因为诊断步骤简直太容易了。”每个人都知道——每个人浴室里都有那个生物标志物检测工具。它叫体重秤。

[原文] [Dave Ricks]: Today, we'll annualize, you know, in the billions of dollars. I think it's the largest prescription platform online in terms of revenue. We run it on Stripe I think.

[译文] [Dave Ricks]: 今天，我们的年化收入将达到数十亿美元。我认为按收入计算，它是最大的在线处方平台。我想我们是在Stripe上运行它的。

[原文] [Host]: And, of course, I'm on the board of Adobe, a software company... I found it fascinating when I first arrived that 90% of the revenue was off a website that they ran.

[译文] [Host]: 当然，我是Adobe董事会的成员，那是一家软件公司……我刚去的时候发现，他们90%的收入都来自他们运营的一个网站，这让我觉得很着迷。

[原文] [Dave Ricks]: I thought that was, "What? This is a great business." A very low-cost business. Very low-cost route to market, global.

[译文] [Dave Ricks]: 我当时的反应是：“什么？这是个很棒的生意啊。”非常低成本的生意。非常低成本的全球上市渠道。

[原文] [Dave Ricks]: What they built on the back of that was a system of negotiating and capture, rent taking, that's not so popular anymore and we can disintermediate them easily.

[译文] [Dave Ricks]: 他们（指传统PBM和药店）在此基础上建立的是一套谈判、俘获和寻租（rent taking）的系统，这套东西现在没那么受欢迎了，我们可以轻易地将他们去中介化（disintermediate）。

章节 23：全球药企市值之王：80法则与碾压诺和诺德 (The King of Pharma Valuation: Rule of 80 & Crushing Novo)

📝 本节摘要：

主持人终于问出了那个显而易见的问题：为什么礼来能成为全球市值最高的制药公司（约8000亿美元），远超辉瑞等同行？Dave Ricks解释说，这是因为礼来不仅仅是一家制药公司，在华尔街眼中，它更像是一家“GLP-1公司外挂其他业务”。他提出了一个惊人的“80法则（Rule of 80）”概念（即利润率+增长率超过80），指出目前只有三家大公司达到这一标准：NVIDIA（英伟达）、Broadcom（博通）和礼来。尽管竞争对手诺和诺德（Novo Nordisk）也在增长，但Ricks透露了一个关键数据：礼来目前在美国新患者中的市场份额已高达75%。华尔街给予其高达50倍的市盈率（行业平均仅12倍），是因为相信它能建立起超越专利周期的“特许经营价值”。

[原文] [Host]: We've been having this conversation for quite some time and we haven't asked you— With one beer. Well, we can rectify that, but we haven't asked you maybe one of the first questions that we ought to have asked you, which is Eli Lilly is the largest pharma company in the world. Why?

[译文] [Host]: 我们已经聊了这么久，却还没问你——虽然只喝了一杯啤酒。好吧，我们可以补上，但我们还没问你那个或许最该先问的问题：Eli Lilly（礼来）是世界上最大的制药公司。为什么？

[原文] [Dave Ricks]: Well, in simple terms, we are kind of a rare situation right now in that our growth rate is high and our profitability is expanding and we are in an early cycle of this invention. I think Wall Street believes—

[译文] [Dave Ricks]: 嗯，简单来说，我们现在处于一种罕见的情况，那就是我们的增长率很高，盈利能力在扩张，而且我们正处于这项发明的早期周期。我认为华尔街相信——

[原文] [Host]: This being?

[译文] [Host]: 这项发明是指？

[原文] [Dave Ricks]: GLP-1s, which is driving probably 80% of the economic value of the company. Our market cap is about—

[译文] [Dave Ricks]: GLP-1药物，这大概驱动了公司80%的经济价值。我们的市值大约是——

[原文] [Host]: You think Eli Lilly is a GLP-1 company with a sidecar—

[译文] [Host]: 你认为Eli Lilly是一家带了个“边车（sidecar，指附加业务）”的GLP-1公司——

[原文] [Dave Ricks]: Sidecar. Of some other of some other stuff? Yeah, that's probably trading like other, okay, so in our sector today, let's pick a company like Bristol Myers or Pfizer. These are big companies with revenues not so different from ours and we compete with them in these other spaces. Their market cap's between $100-$200 billion.

[译文] [Dave Ricks]: 边车。装着其他东西？是的，那部分可能像其他公司一样交易。好吧，在我们今天的板块里，挑一家像Bristol Myers（百时美施贵宝）或Pfizer（辉瑞）这样的公司。这些都是大公司，收入与我们相差无几，我们在其他领域与它们竞争。它们的市值在1000亿到2000亿美元之间。

[原文] [Dave Ricks]: We're trading about $800 billion, and that difference is the GLP-1 phenomena. I think Wall Street also believes that our R&D productivity has been higher. So every dollar we put through the income statement for R&D or through an acquisition, we get a little bit of a premium, a management premium on.

[译文] [Dave Ricks]: 而我们的交易价格大约是8000亿美元，这个差异就是GLP-1现象。我认为华尔街也相信我们的研发生产力更高。所以我们投入损益表用于研发或收购的每一美元，我们都能获得一点溢价，即管理溢价。

[原文] [Dave Ricks]: I think most of the sector is treated the opposite way, which is that that's actually probably going to destroy value in some way. And I think the other thing that's out there is this belief that perhaps, for those that are really long our stock, our belief that perhaps this cycle could be different, this cycle starting with GLP-1s, but that you could create, back to the route to market and the consumer, much more of a self-pay branded business that has staying power beyond—

[译文] [Dave Ricks]: 我认为该板块的大多数公司受到的待遇相反，即认为投入可能在某种程度上会破坏价值。我认为外界还存在另一种信念，对于那些真正长期持有我们股票的人来说，他们相信这个周期可能不同——这个以GLP-1开始的周期——你可以创造出（回到之前的市场路线和消费者话题）一种更多的自费品牌业务，其持久力能超越——

[原文] [Host]: Franchise value.

[译文] [Host]: 特许经营价值（Franchise value）。

[原文] [Dave Ricks]: The patent cycle. Franchise value. Thank you. And I think so far, the evidence is pointing that way.

[译文] [Dave Ricks]: 专利周期。特许经营价值。谢谢。我认为到目前为止，证据都指向这个方向。

[原文] [Host]: You said GLPs are one of the biggest drivers of the business. Eli Lilly's growing at about 30% right now revenues?

[译文] [Host]: 你说GLP药物是业务最大的驱动力之一。Eli Lilly现在的收入增长率大约是30%？

[原文] [Dave Ricks]: 40% year-to-date.

[译文] [Dave Ricks]: 年初至今是40%。

[原文] [Host]: Oh, wow.

[译文] [Host]: 噢，哇。

[原文] [Dave Ricks]: We'll have earnings on, yeah, actually here's a fun fact. There's three scaled large cap companies that have a rule of 80. Can you name them?

[译文] [Dave Ricks]: 我们将发布财报——实际上这里有个有趣的事实。有三家成规模的大盘股公司符合“80法则（rule of 80）”。你能说出它们的名字吗？

[原文] [Host]: Stripe's doing pretty well, but—

[译文] [Host]: Stripe做得不错，但是——

[原文] [Dave Ricks]: NVIDIA must be—

[译文] [Dave Ricks]: NVIDIA（英伟达）肯定是——

[原文] [Host]: NVIDIA is the highest. I think they're over 90. Margin plus growth.

[译文] [Host]: NVIDIA是最高的。我想他们超过90了。利润率加增长率。

[原文] [Dave Ricks]: CoreWeave?

[译文] [Dave Ricks]: CoreWeave？

[原文] [Host]: I think that's, considering you're talking the CEO of Eli Lilly, please. So top hundred market small caps out there.

[译文] [Host]: 我想那是——考虑到你是在和Eli Lilly的CEO谈话，拜托。指的是前一百名市值的公司，不是小盘股。

[原文] [Dave Ricks]: Okay, okay, yeah, yeah, yeah. So it's based quite close to where we're sitting.

[译文] [Dave Ricks]: 好的，好的，是的，是的。有一家总部离我们坐的地方很近。

[原文] [Host]: Genentech?

[译文] [Host]: 基因泰克？

[原文] [Dave Ricks]: Broadcom.

[译文] [Dave Ricks]: Broadcom（博通）。

[原文] [Host]: Of course. Yeah, of course.

[译文] [Host]: 当然。是的，当然。

[原文] [Dave Ricks]: So the hardware guys and AI are killing it. But I think what's interesting to me, they're trading at multiples above ours, there's a belief that their cycle is somehow longer than ours.

[译文] [Dave Ricks]: 所以硬件厂商和AI都表现极好。但这对我来说有趣的是，它们的交易倍数（市盈率）比我们要高，因为人们相信它们的周期在某种程度上比我们的更长。

[原文] [Dave Ricks]: And I think tirzepatide's US patent is late '30s, orforglipron, the oral, beyond that. So, yeah, that's my pitch to investors. But we're in that club as well.

[译文] [Dave Ricks]: 而我认为替尔泊肽（tirzepatide）的美国专利要到30年代末，口服药orforglipron则更久。所以，是的，这就是我给投资者的推介。我们也属于那个俱乐部。

[原文] [Host]: So first off, Novo is growing in the teens. For two companies with GLP offerings that are working, why are those growth rates so different?

[译文] [Host]: 首先，Novo（诺和诺德）的增长率是百分之十几。对于两家都拥有有效的GLP产品的公司来说，为什么增长率相差这么大？

[原文] [Dave Ricks]: We're taking most of the growth in the market.

[译文] [Dave Ricks]: 我们拿走了市场上的大部分增长。

[原文] [Host]: Okay, so just your product's working better.

[译文] [Host]: 好的，所以就是你们的产品效果更好。

[原文] [Dave Ricks]: It's a share. Right now in the US, across all forms of GLP-1, on new patient capture, we're basically 70%-75% right now. So almost three to one.

[译文] [Dave Ricks]: 是市场份额的问题。目前在美国，在所有形式的GLP-1药物中，就新患者捕获率而言，我们基本上占到了70%到75%。所以几乎是三比一。

[原文] [Host]: What would you guess Eli Lilly's P/E is?

[译文] [Host]: 你猜Eli Lilly的P/E（市盈率）是多少？

[原文] [Dave Ricks]: Forward P/E? 50. 5-0.

[译文] [Dave Ricks]: 远期市盈率？50。5-0。

[原文] [Host]: Oh my god.

[译文] [Host]: 天哪。

[原文] [Dave Ricks]: The sector's like 12.

[译文] [Dave Ricks]: 整个板块大概是12。

章节 24：50倍市盈率背后的“蓝海”逻辑与研发赌注 (The "Blue Ocean" of $0 Markets & The 25% R&D Gamble)

📝 本节摘要：

为什么华尔街愿意给礼来高达50倍的市盈率，而同行仅为12倍？Dave Ricks揭示了其背后的核心逻辑：除了GLP-1的成功，投资者更看重礼来的“预测能力”。他列举了公司胜出的三大法宝：更快的周期时间、瞄准“零市场（$0 Markets）”的蓝海战略（如针对未被定义的疾病），以及极其自律的资本配置。Ricks承诺将营收的20%-25%重新投入研发——这意味未来可能达到甚至超越NIH（美国国立卫生研究院）的预算规模。他甚至将购买减肥药Zepbound比作一种“社会契约”：每花一美元买药，就有25美分变成了资助未来阿尔茨海默病等绝症研究的“捐款”。

[原文] [Host]: What would you guess Eli Lilly's P/E is?

[译文] [Host]: 你猜Eli Lilly的P/E（市盈率）是多少？

[原文] [Dave Ricks]: Forward P/E? 50. 5-0.

[译文] [Dave Ricks]: 远期市盈率？50。5-0。

[原文] [Host]: Oh my god.

[译文] [Host]: 天哪。

[原文] [Dave Ricks]: The sector's like 12.

[译文] [Dave Ricks]: 整个板块大概是12。

[原文] [Host]: So what is it that investors have confidence in?

[译文] [Host]: 那么投资者究竟对什么有信心？

[原文] [Dave Ricks]: Well, I think the track record of success. We've been on a growth curve for 12 years or so. It's certainly gone a little more hyperbolic lately. But I think that builds confidence.

[译文] [Dave Ricks]: 嗯，我认为是成功的过往记录。我们处于增长曲线上已经12年左右了。当然最近这条曲线变得有点夸张（双曲线式）。但这建立了信心。

[原文] [Dave Ricks]: And I think we do three things better than others. One we talked about already, which is cycle time. It's a basic concept, but if you can make software faster than someone else, you're going to win. And the same in the drug business.

[译文] [Dave Ricks]: 我认为我们在三件事上比别人做得好。第一件我们已经谈过了，就是周期时间（cycle time）。这是一个基本概念，但如果你能比别人更快地开发软件，你就会赢。制药行业也是如此。

[原文] [Dave Ricks]: The second is prediction of where to tack the investment and allocating a meaningful part to ideas that may not be obvious today, but actually are big problems without markets. And we're drawn to those.

[译文] [Dave Ricks]: 第二是对投资方向的预测，并将有意义的一部分资金配置到那些今天看起来不明显，但实际上是尚未形成市场的重大问题上。我们被这些问题所吸引。

[原文] [Host]: Jensen Huang at NVIDIA talks about how he loves $0 markets and you're describing some of the same things.

[译文] [Host]: NVIDIA（英伟达）的黄仁勋（Jensen Huang）谈到过他如何热爱“0美元市场（$0 markets）”，你描述的东西跟这有点像。

[原文] [Dave Ricks]: Exactly. Blue ocean things that are, you know, there's no limit to human disease. And actually the longer we help people live, the more diseased they'll be. So in a way, it's alike AI in that way where it's like AI begets more AI. It's just this growing machine.

[译文] [Dave Ricks]: 没错。那就是蓝海，你知道，人类疾病是没有止境的。实际上我们帮助人们活得越久，他们患的病就越多。所以在某种程度上，这就像AI一样，AI生出更多的AI。这是一个不断增长的机器。

[原文] [Dave Ricks]: And then I think discipline of the allocation between the types of R&D that are extending the franchise, these moonshots we just talked about... You know, we're doing this study now that I think will be quite interesting that is going to potentially show you can slow Alzheimer's before it starts. That's the kind of thing that could be a mega market.

[译文] [Dave Ricks]: 第三是在各类研发之间的配置纪律，要在扩展现有特许经营权和我们刚才谈到的那些“登月项目（moonshots）”之间取得平衡……你知道，我们正在做一项我认为会非常有趣的研究，可能证明你可以在阿尔茨海默病开始之前就减缓它。那就是可能成为超级市场（mega market）的事情。

[原文] [Host]: In as much as GLP-1s represent this enormous advancement... does that mean that people should now expect Eli Lilly to be far more able to fund broad-based drug R&D than it was in the past?

[译文] [Host]: 既然GLP-1代表了如此巨大的进步……这是否意味着人们现在应该期待Eli Lilly比过去更有能力资助广泛的药物研发？

[原文] [Dave Ricks]: I think so. I have a belief that if you're not generating, to generate double digit growth in the sector, you need to invest at 20%-25% of sales in R&D. That's sort of a positive return R&D stack. And we're doing that.

[译文] [Dave Ricks]: 我认为是这样。我有一个信念，如果你想在这个行业产生两位数的增长，你需要将销售额的20%-25%投入研发。这算是一种正回报的研发堆栈。我们正在这样做。

[原文] [Host]: But do you think, if revenue goes to 120, you know—

[译文] [Host]: 但你认为，如果收入达到1200亿，你知道——

[原文] [Dave Ricks]: I would try to spend 20% of that, which which would then approximate the NIH. And I think that's a frightening thing because, well, how many ideas are out there?

[译文] [Dave Ricks]: 我会尝试投入其中的20%，那样的话（研发投入）将接近NIH（美国国立卫生研究院）的规模。我觉得这是一件可怕的事情，因为，嗯，到底有多少好点子值得投呢？

[原文] [Host]: So you're saying anyone who's on this, you know, who's teetering on the brink of purchasing a GLP-1... They're paying for medicine that's going to help someone else. You're saying that the purchase of this GLP-1 is also a kind of subsidy—

[译文] [Host]: 所以你是说，任何正在犹豫要不要买GLP-1药物的人……他们支付的药费将帮助其他人。你是说购买GLP-1也是一种补贴——

[原文] [Dave Ricks]: For cancer R&D.

[译文] [Dave Ricks]: 补贴癌症研发。

[原文] [Dave Ricks]: But it's important what you're saying about people buying is that a quarter of every dollar you spend is going to a research lab or a clinical trial for a medicine you might not need or for someone you don't know.

[译文] [Dave Ricks]: 但你所说的人们购买这一点很重要，那就是你花的每一美元中，有25美分流向了研究实验室或临床试验，去研发一种你可能不需要的药，或者是为了你不认识的人。

[原文] [Dave Ricks]: That's someone's money. But maybe they'll have Alzheimer's someday and we'll have a solution for that, or maybe someone they know. But that's the virtuous circle we try to drive.

[译文] [Dave Ricks]: 那是某人的钱。但也许有一天他们会患上阿尔茨海默病，而我们会为此提供解决方案，或者也许是他们认识的人。这就是我们要努力推动的良性循环。

[原文] [Dave Ricks]: And just to add on the R&D, the other thing we're doing at some scale is actually trying to create a ecosystem around us of invention that we can aid in a real way, not just own part of it. We've built these things called Catalyze360 or the Gateway Labs here in South San Francisco actually where we host scale-ups, not startups.

[译文] [Dave Ricks]: 补充一点关于研发的，我们在一定规模上做的另一件事实际上是试图在我们周围建立一个发明生态系统，我们可以真正地帮助它，而不仅仅是拥有一部分。我们建立了名为Catalyze360的东西，或者实际上就在南旧金山这里的Gateway Labs，我们在那里托管处于“扩张期（scale-ups）”的公司，而不是初创公司。

[原文] [Dave Ricks]: So rather than hire some consultant who retired five years ago to help you with a particular problem, we'll give you someone working on it right now. And so it's sort of a loosely coupled model without buying them.

[译文] [Dave Ricks]: 所以与其雇佣一些五年前退休的顾问来帮你解决特定问题，我们会给你提供正在处理该问题的人员。这是一种松耦合模式，而不是买下他们。

章节 25：平台与靶点的博弈 & 150年的“人才赌局” (Platform vs. Target & The 150-Year Talent Gamble)

📝 本节摘要：

访谈的最后部分深入探讨了研发的战术细节与企业的长青之道。Dave Ricks区分了两种研发赌注：一种是投资“平台（Platforms）”（如Genentech的单抗技术），旨在抓住整个技术浪潮；另一种是精准的“靶点猎杀（Target Hunting）”，即在成千上万的新发现中挑选出最具潜力的目标。随后，话题转向了礼来150年的历史。Ricks自豪地指出，他是公司历史上的第11任CEO——这一数字甚至比同期的教皇数量还要少一位。这种极度稳定的内部继任文化，建立在敢于对人才进行“终极冒险”的基础上：把人放到他们完全没经验的岗位上去历练。最后，他分享了一条反直觉的管理铁律：尽管研发资金以20%的速度增长，但人员编制（Headcount）必须控制在个位数增长，以防止大公司病。

[原文] [Host]: Is it meaningful to talk about what fraction of R&D is towards specific treatments? Is, like, focused vertical R&D versus I presume you do a lot of horizontal R&D.

[译文] [Host]: 讨论有多少研发投入是针对特定治疗方法的有意义吗？也就是那种聚焦的垂直研发，对比我假设你们做的很多横向研发。

[原文] [Dave Ricks]: Yeah, platforms.

[译文] [Dave Ricks]: 是的，平台（platforms）。

[原文] [Host]: Yeah, exactly, platforms. Because presumably it's even harder to reason out the platforms and the payoffs there.

[译文] [Host]: 是的，没错，平台。因为我想推导平台的价值和回报可能更难。

[原文] [Dave Ricks]: Well, there you need some scale. There's a lot of platform companies that get funded that are biotech. And they are usually exploring a new platform that's quite helpful. That's important work they do. And often we'll partner with them early and try to develop that capability ourselves.

[译文] [Dave Ricks]: 嗯，这方面你需要一定的规模。有很多获得资助的平台型公司都是生物科技公司。他们通常在探索一个新的平台，这非常有帮助。他们做的是重要的工作。通常我们会早期与他们合作，并尝试自己开发那种能力。

[原文] [Dave Ricks]: Basically, in our business, there's two kinds of questions on early phase R&D. One of them is this, is there a new platform that can unlock targets we already know about in new ways or in better ways that create a whole field of drugs?

[译文] [Dave Ricks]: 基本上，在我们的业务中，早期研发有两种问题。一种是：是否有新的平台能够以新的或更好的方式解锁我们已经知道的靶点，从而创造出一整个领域的药物？

[原文] [Dave Ricks]: If you think of Genentech, like, that was a company that exploded based on monoclonal antibody technology by tricking cells to make a human antibody that solved disease. 30-year run of spectacular new medicines. Or Gilead Sciences nearby, which really started on this idea of virology and new virology chemistry and small molecules.

[译文] [Dave Ricks]: 如果你看看Genentech（基因泰克），那是一家基于单克隆抗体技术爆发的公司，通过诱骗细胞制造能解决疾病的人类抗体。那是长达30年的壮观新药历程。或者是附近的Gilead Sciences（吉利德），它真的是从病毒学以及新的病毒化学和小分子的想法起步的。

[原文] [Dave Ricks]: So we want to be there at the early stages because it is like a catching a wave thing. If you're late, you miss it all. And so that's a kind of investing we do and that's a more scaled project.

[译文] [Dave Ricks]: 所以我们希望在早期阶段就参与其中，因为这就像是“抓浪（catching a wave）”。如果你晚了，你就错过了一切。所以那是我们做的一种投资，那是一种更具规模的项目。

[原文] [Dave Ricks]: And then the other kind is, like, picking targets and looking in the broad space of biologic discovery and say, "Okay, of the thousand things uncovered this year, these 15 we think could be highly relevant and we're going to put a team around those."

[译文] [Dave Ricks]: 然后另一种是挑选靶点（picking targets），在广阔的生物发现空间中观察并说：“好吧，在今年发现的一千件事物中，我们认为这15个可能高度相关，我们要围绕它们组建团队。”

[原文] [Dave Ricks]: This isn't the Skunk Works kind of allowable deviation or whatever I said earlier. But it's a purposeful thing to say, "Let's drug hunt here. Let's use the tools we have and assault those targets with multiple ones of those tools and see if we can get a drug out of it."

[译文] [Dave Ricks]: 这不是我之前说的那种“臭鼬工厂（Skunk Works）”式的允许偏差。而是一件有目的的事情，即“让我们在这里进行药物猎杀（drug hunt）。让我们利用手中的工具，用多种工具攻击这些靶点，看看能不能从中搞出一种药来。”

[原文] [Host]: Eli Lilly is more than a hundred years old and—

[译文] [Host]: Eli Lilly已经有一百多年的历史了，而且——

[原文] [Dave Ricks]: 150 in May.

[译文] [Dave Ricks]: 到5月份就150年了。

[原文] [Host]: Oh, wow. Okay, so coming up on your 150th birthday. And I noticed that often very tenured, successful companies are quite serious about, and good at, internal succession planning.

[译文] [Host]: 噢，哇。好的，所以马上就是你们的150岁生日了。我注意到，通常那些历史悠久、成功的公司都非常重视并且擅长内部继任计划。

[原文] [Host]: I think about, you know, Royal Dutch Shell or, you know, companies like that, and Eli Lilly. You joined in what year?

[译文] [Host]: 我想到了像皇家壳牌（Royal Dutch Shell）那样的公司，还有Eli Lilly。你是哪一年加入的？

[原文] [Dave Ricks]: 1996.

[译文] [Dave Ricks]: 1996年。

[原文] [Host]: Right, you joined in 1996. Not as a hired CEO. And you were rotated across, you know, the business. You ran China, you ran the US business. Development.

[译文] [Host]: 对，你1996年加入。不是作为空降的CEO。你在业务各个部门轮岗。你管过中国区，管过美国业务。还有业务拓展（Development）。

[原文] [Dave Ricks]: Exactly. New hire.

[译文] [Dave Ricks]: 没错。（当时只是个）新员工。

[原文] [Dave Ricks]: You know, we've had 150 years of that and I'm the 11th CEO of the company. That's one less than popes in that period of time. So it is a special honor actually, and it's not a lifetime appointment. I can be fired any day.

[译文] [Dave Ricks]: 你知道，我们经历了150年的历史，而我是公司的第11任CEO。这比同期的教皇数量还要少一位。所以这实际上是一种特殊的荣誉，但这并不是终身制。我随时可能被解雇。

[原文] [Dave Ricks]: But the first four were family members and then we've had a lot of long-running successful and only one external.

[译文] [Dave Ricks]: 但前四任是家族成员，之后我们有很多长期任职且成功的CEO，只有一位是外部聘请的。

[原文] [Dave Ricks]: And I think that's part of the success of the company is that in scaled companies... not one person cannot possibly really lead the whole thing. You have to know the role you have to play and you have to have others around you that can do it. By creating that environment, giving up some of that, you actually grow people and you grow people in a special way.

[译文] [Dave Ricks]: 我认为这是公司成功的一部分原因。在成规模的公司里……没有一个人能真正领导所有事情。你必须知道你该扮演的角色，并且你周围必须有能胜任的人。通过创造这种环境，放手一部分权力，你实际上是在培养人，而且是以一种特殊的方式培养人。

[原文] [Dave Ricks]: A way that they know how to operate in the unspoken operating system called culture.

[译文] [Dave Ricks]: 让他们知道如何在一个名为“文化”的潜规则操作系统中运作。

[原文] [Dave Ricks]: And, like, one of my things now as we grow so fast is, like, keep headcount flat. And that's makes me very unpopular 'cause people are like, "What? Like, how do I get this work done?"

[译文] [Dave Ricks]: 比如，我现在做的一件事——尽管我们增长如此之快——就是保持人员编制（headcount）持平。这让我非常不受欢迎，因为人们会问：“什么？那我怎么把活干完？”

[原文] [Host]: Are you growing in R&D as you grow the spend?

[译文] [Host]: 你们在增加支出的同时，R&D部门的人员在增加吗？

[原文] [Dave Ricks]: Slightly but, so we're growing R&D high teens, low 20s. We're growing headcount in R&D single digits. So where does the money go?

[译文] [Dave Ricks]: 稍微增加一点，但——我们的R&D支出增长率是百分之十几大到二十几（high teens, low 20s），但R&D人员增长率是个位数。那么钱去哪儿了？

[原文] [Dave Ricks]: So the money goes to projects. Yeah, and salary... but clinical trials, new equipment, new laboratories. Supercomputers from NVIDIA, that's expensive.

[译文] [Dave Ricks]: 钱流向了项目。是的，还有薪水……但主要是临床试验、新设备、新实验室。NVIDIA的超级计算机，那可是很贵的。

[原文] [Dave Ricks]: And I look at my career and probably four or five times I was put in a job I had no business being in, but somebody thought I could learn it and that the output of that would be good performance at the end, not at the beginning, and then a better long-term thing for the company.

[译文] [Dave Ricks]: 回顾我的职业生涯，大概有四五次，我被放到了一个我完全没资格（no business being in）的岗位上，但有人认为我能学会，并且认为最终的产出会是良好的表现——虽然不是在一开始——这对公司来说是一件更好的长远之事。

[原文] [Dave Ricks]: I'm so grateful for that because that's like ultimate risk taking on people and I would not be here without those successive jobs where I was like, I never would've gotten them if I applied externally, but the company gave them to me.

[译文] [Dave Ricks]: 我对此非常感激，因为那就像是对人才进行的“终极冒险（ultimate risk taking）”。如果没有那些接连不断的职位，我就不会坐在这里——如果是去外面应聘，我绝对拿不到那些职位，但公司给了我机会。

[原文] [Host]: A lot of companies say they're long-term oriented, but I feel like this is a particular example of revealed preference. David, thank you. Awesome conversation.

[译文] [Host]: 很多公司都说自己是长期导向的，但我觉得这是一个特别明显的“显示性偏好（revealed preference）”的例子。David，谢谢你。非常棒的谈话。