#249 阿尔伯特·布尔拉:辉瑞 CEO

#249 – Albert Bourla: Pfizer CEO

第 249 期··嘉宾 / 主题:阿尔伯特·布尔拉·中文精读文稿
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中文精读由 AI 基于原始访谈改写,仅供学习参考。

2020年11月8日下午两点,康涅狄格州一间很小的办公室。五个人,几杯咖啡,一些互相调侃的玩笑。

他们在等一个电话。

电话那头是数据监查委员会(Data Monitoring Committee),一组与辉瑞无关的独立专家。他们手里有揭开盲态的权限,能告诉辉瑞:III期临床试验的疫苗,成了,还是没成。

电话比预定时间来得晚。等待的几个人越等越焦虑,只能互相打趣,喝咖啡,讲笑话。等到两点左右,铃声响了。

自由了,解放了,开心。就像压在我肩上的一块巨石被卸了下来。(阿尔伯特·布尔拉)

他转头对团队说了句“我爱你们”。“我们地中海人就是这么说话的。”布尔拉和 Lex Fridman 聊起这个细节时笑了笑,又补了一句,“也许你们俄罗斯人也这样。”

23亿美元,一次全押

辉瑞和 BioNTech 合作的这款疫苗,研发投入是23亿美元左右,折合人民币接近150亿。

这笔钱特别的地方在投法。

药企做研发有一套惯常的风控节奏:先花5000万美元摸底,数据不错再投5000万,再有进展再加1个亿。每一步都留退路,每一步都看前面的结果再决定下一步。这套节奏把风险摊薄了,代价是把时间也摊薄了。

布尔拉把所有的钱一次投了进去。

通常我们花5000万,如果顺利,再花5000万,再顺利,再花1亿。这一次,我们一次性把23亿全部押上,这样不损失时间。(阿尔伯特·布尔拉)

他形容这个决定谈不上艰难。2020年初那种情况下,恐惧笼罩着所有人,包括辉瑞自己的员工,没人知道明天长什么样。既然手里有能帮忙的东西,就没有第二个选项。

这话听起来像公关辞令。但如果把辉瑞当时的财务结构摊开看,这个决定的分量会更清楚。

研发新药的公司,本质是在做一场概率生意。候选分子在临床阶段的淘汰率高得惊人,活下来的那一小部分要连本带利把所有人的投入赚回来,所以药价里天然含着失败的成本。一次性押上23亿,等于是把未来几年好几个项目的容错空间,全部压在一条赛道上。成了,一切好说;不成,股东要问话。

Fridman 追问了一句很多人心里的话:你是CEO,公司要赚钱,这个决定里有几分是救人,几分是财务计算?

我很清楚,如果你太专注于赚钱,你永远赚不到钱。你应该专注于真正的价值驱动是什么。真正的价值驱动,是做出改变患者生命的突破。你不做这个,永远赚不到钱;你做了,别担心,钱会跟着来。(阿尔伯特·布尔拉)

这套逻辑听着像心灵鸡汤,其实是制药行业最朴素的商业常识。专利保护期一到,仿制药蜂拥而上,价格断崖式下跌。一款药能赚多少钱,几乎完全取决于它在专利期内能不能做到别人做不到的事。“做个好药”在这个行业里从来都是唯一可持续的商业模式。

速度快,不等于流程短

外界对新冠疫苗最大的疑问之一是速度:一款常规疫苗从零到上市要八到十年,这个不到一年就打了。安全测试是不是被压缩了?

布尔拉给出的答案反过来了:流程一步没少,少的是等待和犹豫。

疫苗研发通常分几个阶段。先是从几十个候选方案里筛,辉瑞最初试了20种,一路筛到4种,再到2种,最后定下1种。然后是剂量摸索,从低剂量开始打进人体,逐步加量,同时监测免疫反应和不良反应,还要覆盖不同年龄段,年轻人、老年人分开看。接着是接种方案,第二针隔三周、四周还是六个月,都要试出来。

这些做完,才轮到III期临床。这一步是真正烧钱的环节,辉瑞这次花了接近10亿美元。所以正常流程里,企业会在进入III期之前反复做实验,尽可能确认手里这个就是对的,才敢把10亿美元押上去。

辉瑞把这段“反复确认”的时间砍掉了,用钱换。III期临床本身的设计、盲法、安慰剂对照,一条规则都没改。

注射疫苗的医生不知道他打的是安慰剂还是疫苗,他只知道一个条码。只有计算机知道。要进入那台计算机,至少需要两个人同时插入钥匙。这些人有法律义务,在任何情况下都不能提前查看数据。(阿尔伯特·布尔拉)

提速的地方在招募。正常一款疫苗的III期临床,30家医院参与,招满5万人要一年。辉瑞把参与的医院扩到150家,三四个月招

满。多出来的成本很直白:150家医院同时开动,人力、协调、管理,全是钱。

真正的加速度来自目标设定。

辉瑞过去十年每年的疫苗总产量是2亿剂。这次布尔拉给生产团队的任务是30亿剂,一款全新疫苗。正常一个新分子的发现阶段要四年,新冠口服药的发现阶段,他给的时间是四个月。

当你设定这种目标时,他们立刻就知道,不能只在框框里思考。这时候人的聪明才智和心就出来了。这就是他们让所有人惊讶的方式。(阿尔伯特·布尔拉)

他反复强调一句话:人对自己能力的估计,通常严重偏低。给一个看起来不可能的任务,人才会跳出框框。

FDA那75年,和一段不肯让步的追问

访谈里有一段气氛明显变紧。

FDA 当时面对一项诉讼,被要求公开辉瑞疫苗的审评数据。FDA 提出的时间表是按75年来披露。这个数字一出来,各种猜测都冒了出来。

布尔拉的回答是标准的合规口径:辉瑞和监管机构的往来一直很透明,有法律强制要求公开双方的沟通内容,他不清楚FDA为什么要这么久,但他相信FDA有很好的理由。

Fridman 没有放过这个问题。他说,这看起来不像一个好理由。他提到,75年这个数字的来源,很可能是FDA内部设定的审评速度,比如每天只能处理500页文件。这是典型的官僚机制:规则本身合理,累积起来的效果荒唐。

政府很擅长制定规则、确保对企业和个人的监督。但它们会让事情变慢,这是特性,也是缺陷。在这个案例里,它们慢到了这个程度。我认为FDA有潜力成为这个国家最伟大的机构之一。而这一个例子,在我看来是失败的。(Lex Fridman)

布尔拉的回应值得琢磨。他说,这算不上一个黑箱。审评流程是公开的,所有人都知道规则;FDA 里有水平极高的科学家,欧洲的、英国的、日本的监管机构也一样,他们会钻进非常细的细节;而且按照法律,每一项研究的关键内容都会写在产品说明书里,那是一份非常详细的文件。

这段回答技术上没错,但它绕开了问题的核心。Fridman 追问的重点落在“当公众有疑问时,机构为什么选择沉默”,流程本身是否存在根本不是他在问的东西。

有时候问题出在沟通的笨拙和沉默上,流程并没有失败。在很多人明显感到不安、有疑问的时刻,沉默本身就是问题。你应该站出来,解释清楚为什么,而不是让不信任一点点积累、发酵。(Lex Fridman)

这段话点到了一个关键机制:信任的流失很少来自某一次具体的错误,更多来自“我有问题,但没人回答我”这种持续的悬置感。悬置久了,空白会被别的东西填满。

那道从FDA通向辉瑞的门

乔丹·彼得森(Jordan Peterson)托 Fridman 带了一个问题:辉瑞、FDA、CDC 之间存在密切的人员流动,很多人在FDA工作过,现在在辉瑞;也有人反过来。这种旋转门会不会影响监管的公正性?

布尔拉的回答很直接:零怀疑。

为了强化这套系统,他们设了很长的时间壁垒。如果一个人从产业界进入FDA,在一段时间内他不能处理相关议题;如果是他曾经任职的公司,这个期限还要更长。(阿尔伯特·布尔拉)

他补充说,难的决策会引入外部专家,容易的决策由内部专家反复辩论,有分歧就往上抬。这套自查和制衡机制,在CDC和FDA内部都存在。

Fridman 在这里做了一件很少见的事:他讲起了自己的来历。

他成长于苏联,那个环境里,贿赂是办事的默认路径。被警察拦下来,给钱是常识,这就是生活方式。后来到了美国,看到法治有这么大的力量,他觉得美。

但他仍然担心人性。

当你看到一些人的简历上,既有辉瑞的经历,又有FDA、CDC的经历,这会让人不安。这些本该被视为权威的领导者,究竟有没有在跟公众玩一场游戏?(Lex Fridman)

布尔拉承认 Fridman 描述的苏联经验是真实的,也承认有些国家确实需要那样做事,但他认为美国这些机构不是这样,它们有很高的诚信记录。他相信绝大多数美国人、欧洲人、英国人、以色列人,信任FDA、EMA、CDC、MHRA说的话。

这个判断在2021年底就已经显得乐观。它的局限在于把信任当成了一个静态存量:只要机构历史上可靠,公众就该继续信任。可信任是动态的,每一次沉默、每一个75年,都在扣减它。

声誉是桶漏滴收的生意

Fridman 提到了一个绕不开的名字:Bextra。

2009年,辉瑞承认对关节炎药物 Bextra 进行非法营销,同意支付23亿美元和解。这是美国历史上最大的医疗欺诈和解案之一。

布尔拉没有回避,他把时间线拆开讲:2009年的案子,对应的是2003年的行为。

2003年发生的事情,基本上是我们几个销售代表做了标签外推广。他们和医生谈论了产品的标签外用途,而他们不应该这么做。(阿尔伯特·布尔拉)

他解释了标签外的含义:FDA批准的适应症之外,这款药可能还有别的疗效。医生之间讨论这些研究是允许的,制药公司不能主动向医生推荐这些未获批的用途。

罚款金额的构成,他也讲得很坦白:这笔钱对应的并非行为的严重程度,它按营收规模来算。Bextra 是个大产品,所以罚得重;如果是个小产品,罚得就轻。

2003年发生的事非常糟糕。我不认为那之后还发生过类似的事。从2009年到现在,我们在遵守每一条法规和规则上有出色的记录。(阿尔伯特·布尔拉)

关于公众信任,他说了一句在这个访谈里最像格言的话。

声誉是可以用桶丢掉、用滴赚回来的东西。一旦失去,你需要付出巨大努力才能拿回来。制药行业失去过它。很清楚,过去十年这个行业的声誉跌到了历史最低点。(阿尔伯特·布尔拉)

他承认原因之一就是行业自身的行为。但他也给出一个观察:新冠期间,私营部门拿出了检测、呼吸机、治疗药物、疫苗。他认为这向世界证明了私营生命科学部门对社会的价值,也改善了辉瑞的声誉。

紧接着他补了一句自我约束:他不会把这份声誉当成理所当然。

广告、赞助,和那种说不清的压力

Fridman 提到乔·罗根(Joe Rogan)指出的现象:辉瑞在主流媒体上投放了大量广告。他的问题落在隐性压力上,广告合不合法倒在其次。

人们看主流新闻,是想知道这世界到底怎么了。如果辉瑞是很多节目的赞助商,节目在讨论辉瑞时会不会不自觉地手软?这种影响很微妙,但在规模上可能很严重。

布尔拉否认了激进营销的说法。他给出的理由是:处方药广告受到严格监管,不能提任何未获批的用途,而且FDA强制要求广告里必须同时说明药物的不良反应,有时候讲坏处的时间比讲好处还长。

人们有权知道,如果有这样的产品存在,他们应该了解。(阿尔伯特·布尔拉)

关于赞助,他给了一个具体的数字:辉瑞的赞助非常少,而且每一个项目,哪怕2000美元,都有专门团队评估是否存在利益冲突、被赞助方或节目的声誉如何。他说辉瑞的赞助更多集中在患者组织,会刻意避开那些“即使不被影响,也可能被看起来像被影响”的场合。

Fridman 在这段里没有继续逼问,转而讲了一段自己的经历。

他到MIT之后有点失望,甚至有点心碎。他本以为在一个资金充裕的地方,人们会全力做最好的工作、互相支持、为彼此的成功庆祝。现实是,即使钱很多,人们仍然感到财务压力,而这种压力没有激发出他们最好的一面。

我不想把一切都归咎于钱。但当你有了赞助商,我个人会担心,它不会把人身上最好的东西激发出来。(Lex Fridman)

这段话值得停一下。它讲的并非腐败,它指向一种更日常的东西:当一个组织的话语权和经济来源高度重叠,很多微妙的自我审查不需要任何人下指令,会自己发生。这种机制很难取证,也很难反驳,因为它从来不留下痕迹。

没有哪个医疗产品被这样检测过

关于安全性,布尔拉给了一个在这个访谈里最强硬的判断。

人类历史上,没有任何一个医疗产品被如此大规模地检测过。它已经被接种到数亿人身上。因为新冠的重要性,这些人被持续审视。现在全世界的卫生机构都在追踪每一个信号,看接种者身上发生的事是否与疫苗相关。(阿尔伯特·布尔拉)

他补充了机制层面:电子病历能告诉研究者,一个人在什么时间接种、之后发生了什么。他说,现在对这款疫苗安全性的确定程度,比任何其他产品都高,和说明书上写的一致。

Fridman 在这里做了一个自我限定:他自己打了两针辉瑞,他关心的是科学家和科学传播者在沟通上做错了什么,疫苗本身安不安全倒在其次。

我听过的一些科学传播者让我很失望,因为他们说话没有共情。他们没有把自尊心放到一边,真正去听别人说话。那些人没有博士学位,可能大学都没上过生物课,但他们有孩子,他们害怕,他们不知道该信谁。(Lex Fridman)

他特别点出了一个结构性问题:这些人不知道该不该信辉瑞的CEO,因为CEO可能有别的动机,可能只在乎钱。他们只能用常识去提问。科学家对这些人的态度,常常是居高临下的,甚至翻白眼。

布尔拉接住了这段,而且接得很实。

谦逊是一种美德。你受过教育,并不意味着你有谦逊、有共情,或者有良好的人格品质。教育从来不是、也永远不会是衡量这些美德的指标。那些这样做的人错了,而且他们实际上没有为公共卫生服务,因为他们在削弱它。人不蠢。他们能看出你不尊重他们,不尊重他们了解情况的需要,而这关系到他们自己、他们的母亲、他们的孩子的健康。(阿尔伯特·布尔拉)

他给了一个判断:现在没接种的人,绝大多数是因为害怕,没有别的议程。真正有议程的是一小部分人,他们从这种焦虑里赚钱。

CEO被FBI逮捕了,和一张妻子的照片

布尔拉讲了一个自己的经历。

有人在网上写:辉瑞CEO被FBI逮捕了。他看到了,笑了。他说,行吧,他们已经到了这个地步。

这个谣言的用意很清楚:在人们心里种下怀疑。如果FBI都抓了他,那这疫苗我大概不能打。

一周后,同一个网站发文说,辉瑞CEO的妻子死了。文章里配了他妻子的照片。

有人发给我,这次我不笑了,我生气了。我赶紧找我的孩子,告诉他们:如果你们看到什么,妈妈没事,别担心。然后我想起来,她在希腊还有年纪很大的父母。我们开始打电话过去,确保他们知道。(阿尔伯特·布尔拉)

他点出了这件事的性质:写这些东西的人非常清楚他妻子没有死,也非常清楚她会因为接种疫苗后死亡这个叙事被放进标题。这是有意为之的叙事建构,目的是从普通人的压力和焦虑里获利。

这段话是整场访谈里布尔拉最不像CEO的一段。他没有讲数据,没有讲流程,只讲了他怎么给希腊的岳父母打电话。

Fridman 在这里做了一个对称的提醒。人们用常识去怀疑政客和权势人物,这个本能是对的,同样该用来怀疑那些靠“他们在骗你”赚钱的人。他自己都惊讶,靠制造这种怀疑能赚多少钱。

独立思考,带着开放的心态批判性思考。每个人都有可能操纵你,但每个人也都有做好事的能力。(Lex Fridman)

他一再强调的那个100%

Fridman 提了一个有点尖锐的问题:布尔拉在推特上发过疫苗有效性100%这类数据,这算不算过度呈现?即使技术上说没错,也可能被误读。

布尔拉的反应很快:我从没说过100%。

每次我讲话,如果出现100%这个数字,我会赶紧补一句:在生物学里,没有什么是100%的,因为样本量一旦上去,就不会是100%。(阿尔伯特·布尔拉)

他解释,研究中确实有100%的项目,比如死亡保护,比如南非那组数据。但他强调,样本量扩大后,100%会变成95%、96%,方向才是重点。

他说自己发推非常谨慎,而且有人会给他提供第二、第三意见,确保不会造成误解。原因他也说了:他知道人们正在听他说每一句话,他既要表达清楚,也要维持信任。

我不认为一个只挑信息、只强调正面的人,是值得信任的人。我希望我和辉瑞是被信任的。(阿尔伯特·布尔拉)

关于加强针,他给了一条时间线,也给了自己一个说明。疫苗刚出来那几个月,人们问要不要再打一针,他的回答是不知道。到了2021年4、5月,第一批数据出来,他开始说,第二针之后8到12个月可能需要加强针,之后大概率是每年接种。他每次都会加一个前提:在没有新变异株的情况下。

然后Delta来了,加强针的时间点从6个月提前到3个月。现在Omicron来了,两针可能不够,三针有效,很多国家已经把第三针提前。

关于会不会需要专门针对Omicron的新疫苗,他的回答很谨慎:不知道,未来几周会有更多数据。如果需要,我们能做出来。他给了一个产能数字:目前大约每季度10亿剂,一年40亿剂。如果一半产能切换到新疫苗,一半保留旧疫苗,全年仍然是40亿剂。

强制接种:他在辉瑞做了,不建议国家做

Fridman 问了疫苗强制令。布尔拉的回答可以拆成两层:作为雇主的决定,和对国家政策的看法。

作为雇主,他做了强制接种。执行时留了健康、宗教等豁免。做这个决定的时候,辉瑞的员工接种率已经是90%,强制令把它推到了96%。

那10%里有一部分人是永远不会动的,我感觉。因为无论如何,有一小部分人是真的害怕,他们打心底里不舒服。在我们这个案例里,它起作用了,把接种率推到了96%。(阿尔伯特·布尔拉)

他补了一句很人性的账:这6个百分点对应的那些人里,会有很多人不得病,会有一些人不会死。

但问到国家层面,他把决定权推回给了各国的公共卫生官员,说这不该由他回答。

Fridman 在这里给出了明确的反对意见,理由落在自由上,跟医学无关。

从苏联出来的我,认为在公共层面、联邦层面搞强制令是个很糟的主意。即使它对全民健康有好处,这个国家有一种东西叫保住自由,它非常有力量。费尽力气去说服人们接种,让他们自己选择接种,同时保留不接种的自由,这才是真正有力量的东西。对我来说,直接强制是很懒的做法。(Lex Fridman)

这段话背后的逻辑是:强制能快速提高数字,它消耗的是社会信任这笔本金。用一次强制换来的接种率,可能让下一次公共健康动员变得更难。

孩子、恐惧,和一个父亲的立场

关于儿童接种,布尔拉的态度很明确:应该打,5到16岁都该打。

Fridman 请他站在反对者的立场上做一次最强的论证。布尔拉没有直接接这个招,他讲了一个在疫苗获批前遇到的场景。

我遇到过很多家长,他们非常害怕,但怕的是没有疫苗,疫苗本身反而不在他们的恐惧里。他们对着我喊:把疫苗给我,什么时候给我,我真的很害怕。我觉得这不公平:我打了,我丈夫打了,我大儿子打了,而我那个小宝贝,因为年龄不够,没有保护。(阿尔伯特·布尔拉)

他说,现在反过来了,有些家长怕的是疫苗本身,人数少一些,但他们更怕的是孩子出事,因为父母爱孩子胜过爱自己。

Fridman 继续追问:孩子感染后的重症率和死亡率确实很低,这个怎么算?

布尔拉的回答是:低,但孩子确实会死,确实会进医院。他加了一个常被忽略的维度:学校一旦出现病例就得停课,这种中断对孩子健康和成长的代价同样真实。

他拿小儿麻痹做对比:现在还有几个孩子得小儿麻痹?比因新冠住院的孩子少得多。所有人都在打这个疫苗。Fridman 指出小儿麻痹对孩子的致死率更高,布尔拉的回答是:现在不高了,那为什么还要打?因为需要保护。

这段对话里,Fridman 提了一个更根本的问题:mRNA 是第一次大规模用在人身上。家长给孩子做决定时,是在替一个不能自己决定的人承担风险。

布尔拉把立场转了一下:

选择给孩子接种,是选择让某个东西不能伤害他们,那个东西就是疾病。这就是我们一直以来做疫苗的原因。我知道有人为自己、为孩子担心。但我是一个科学家,也是一个父亲。我告诉你们,疫苗对孩子是很好的东西。(阿尔伯特·布尔拉)

这段话在逻辑上成立,它没有正面回应新技术的具体担忧。对一个本来就犹豫的家长来说,“我是科学家也是父亲”这种身份背书,抵不过“这个技术以前没这么大规模用过”这个事实性疑问。整场访谈里反复出现同一个模式:辉瑞能给出极其扎实的流程数据,面对未知的不确定性时,给出的往往是信心,缺少的是不确定性的边界。

五天,一天两次,住院率从十降到一

访谈后半段,话题转到了口服药 Paxlovid。布尔拉在这里的语气明显更兴奋,他用了真正的游戏规则改变者这个说法。

机制很直白:这是给已经感染新冠的人用的。连续五天,早晚各一次,一天两次,一共五天疗程。

原本十个人会住院,现在只有一个会住院。(阿尔伯特·布尔拉)

他提了一个前提:这个数据样本量小,没有人死亡,所以在死亡保护上是100%有效。他立刻补了限定:真实世界里样本量一大,可能就是99%而不是100%。

即便打了折,这个数字对医疗系统的意义仍然很大。他点出了欧洲和美国每次疫情高峰时真正的问题:ICU满了,医院瘫痪了,择期手术要推迟,其他手术要推迟,因为没有床位。一款能让人待在家里、不用住院、不会死亡的口服药,直接卸掉的是整个医疗系统的压力。

关于伊维菌素(ivermectin),Fridman 问得很直接。布尔拉的回答也很直接:

作为科学家,我和我们的科学家讨论过,他们看不到任何理由,让一个寄生虫药能作用于新冠。他们没有看到任何一篇论文描述有人用了它产生了效果。我不认为有任何一篇发表在同行评审期刊、任何可靠科学期刊上的论文支持这个说法。我们专注于救人,不专注于荒唐的东西。(阿尔伯特·布尔拉)

Fridman 做了反驳:确实有不少论文,只是研究规模小,没有决定性证据。

布尔拉的回答是:我没见过可靠的,不管大小。有些大样本研究已经被撤稿,说明它们不成立。

他提到了更早的氯喹,说了一句“我的天”,然后反问:有多少人因为那个死了?

这段对话的价值在两种认知路径的对照。Fridman 的路径是:证据不足,所以保持开放,等更多数据。布尔拉的路径是:机制上说不通,所以不必等。前者更符合科学哲学,后者更符合药物开发的工程效率。两种路径在大部分时候会得出同样的结论,在证据尚未充分的真空地带,它们会分道扬镳。

死亡是生命最伟大的发明

访谈最后,Fridman 问了两个大问题。第一个是:你会想到自己的死亡吗?你怕死吗?

布尔拉的回答很诚实,也很普通。

我年轻时和很多人说过,我不怕死,我根本不在乎。我第一次开始觉得我想活下去,是在有了孩子之后。然后我开始想,天哪,我希望能活着看到他们结婚,希望他们还能看到自己的孩子。所以如果说有什么让我害怕,那就是我可能不再参与他们的生活,我不能再看着他们了。我希望上面有另一个世界,这样我就能从上面看着他们。(阿尔伯特·布尔拉)

Fridman 接了一句:从上面,视野不错。

第二个问题是:生命的意义是什么。他只给了布尔拉两分钟。

布尔拉引用了乔布斯的一句话:死亡是生命最伟大的发明。它清除旧的,给新的让出位置。

生命就是向前走,生命就是创造新东西。也许每个人都是贡献者,但没有谁是拥有者。永远在创造新的东西,永远如此。往这个世界上添加一点美,也许再加一点爱。(阿尔伯特·布尔拉)

这场访谈播出时是2021年12月,Omicron 刚开始扩散。几年后再看,有些判断被验证了,有些没有。加强针成了常态,年度接种也成了很多国家的安排。对机构和药企的信任,没有随着数据积累而回升,反而继续下滑。

这场对话里最值得记住的东西,藏在一个结构性矛盾里:

做出突破需要极高的效率,维持信任需要极高的透明和极慢的耐心。这两件事在同一家公司、同一套流程里,天然冲突。

辉瑞把疫苗的开发周期压缩到了极致,靠的是把钱、把风险、把组织惯性全部一次性押上。这套打法在科学上极其成功,在沟通上几乎必然失败。它没有给解释留出时间,也没有给疑问留出位置。等到疑问积累起来,再想用数据去回答,已经晚了。

Fridman 在节目开头说了一段话,值得原样记住:

有一群人告诉你,只有他们掌握真理,政府会救你,公司会救你,科学、权威、专家、机构会救你。还有一群人同样告诉你,只有他们掌握真理,政府会害你,公司会害你,科学、权威、专家、机构会害你。这两群人中都有善意的和恶意的,都有英雄和骗子。而我认为残酷的事实是,这个世界上没有人能绝对确定地告诉你,谁是谁。你必须用你自己的头脑。(Lex Fridman)

如果你要在这件事上做出自己的判断

  • 分清三层问题:药物本身的安全性和有效性,是可以用数据回答的医学问题;监管机构的披露节奏,是行政和治理问题;公众人物的表达方式,是传播问题。三层混在一起讨论,永远得不出结论。
  • 看数据时先看样本量和置信区间,再看结论。100%在小样本里没有意义,它只说明还没观察到,不说明不会发生。听到任何一方给出极端数字,先问样本有多大。
  • 对旋转门保持警惕,同时往前再走一步:查具体的人、具体的决策。这个人在什么时间、以什么身份、参与了哪个审批。泛泛的怀疑没有信息量,具体的追查才有。
  • 对靠制造恐惧获利的人,和对靠掩盖问题获利的人,用同一套标准。前者说“他们都在骗你”,后者说“一切都没问题”,这两种话都在替你做判断。真正的信息通常带着限定条件,听起来没那么痛快。
  • 接种、加强针、给孩子接种,这几个决定可以拆开做。疫苗对重症的保护、儿童感染的低风险、新技术的长期不确定性,是三个独立的判断。不必因为其中一项存疑,就推翻全部。
  • 遇到看不懂的医学声明,去找原始论文,别停在二手解读。看摘要、看样本量、看有没有对照组、看有没有被撤稿。这四步能过滤掉绝大部分噪音。
文稿来自公开 Kaggle 数据集(rajneesh231/lex-fridman-podcast-transcript),为早期自动转录存档,可能存在识别错误。
The following is a conversation with Albert Berla, CEO of Pfizer. If you'd like to skip ahead to our conversation, the timestamps as always are below. But if not, please allow me to say a few words about truth and human nature. Specifically, about two groups of people throughout history that seek to lay claim to the truth. The first group will tell you that only they possess the truth, and that the government will save you, the company will save you, the science, the authorities, the experts, the institutions will save you. The second group, too, will tell you that only they possess the truth, and that the government will hurt you, the company will hurt you, the science, the authorities, the experts, the institutions will hurt you. Both groups have the benevolent and the malevolent, their heroes and their charlatans. And I think the hard truth is that no one in this world can tell you with absolute certainty which is which. You have to use your mind. This is the burden of being human, of being free. Don't blindly follow any leader, neither the emperor nor the martyr who points out that the emperor has no clothes. And then there's the lessons of history. Vaccines have saved hundreds of millions of lives in the past century, and in general, the advance of medicine has saved billions of lives. If you ignore the power of science, you're not being honest with the lessons of history. And if you ignore the corrupting nature of power and money within institutions, including governments and companies that led to the suffering and death of hundreds of millions in the past century, you are once again not being honest with the lessons of history. I announced that I will be having this conversation with Albert Burla, Pfizer CEO, and a lot of people wrote to me. I would like to say that I was and am and always will be listening and learning with an open mind from everyone. My own opinion, worth little as it is, is that the development of the COVID vaccines is one of the greatest accomplishments of science in recent history. For the rest, from safety and efficacy to policy and economics, I stand humbled before a complicated world full of fear and anger. A small number of malicious people from all walks of life will use that fear and anger to divide us, because the division makes them money and gives them power. I took two shots of the Pfizer vaccine. This was my decision. I don't ever want to force this on anyone, and I certainly don't want to dismiss your concerns or worse, you as a person if you choose not to get vaccinated. I can assure you one thing, in this conversation, and in any conversation, the choice of questions I ask and words I say is mine and mine alone. When my words fall short, as they often do, it is only because of the limitations of my mind and of my speaking ability. It is not due to pressure or fear. I'm not afraid of anyone. I cannot be bought by anyone with money, power, or fame. I hope to prove this to you and to myself in the coming years. This life is short, and to me, without integrity, it is not worth living. People sometimes talk down to me, call me naive. Perhaps they are right, but it is who I am. I think this life, this world, this, our human civilization is beautiful. And as Dostoevsky said, beauty will save the world. This is the Lex Friedman Podcast, and here's my conversation with Albert Borla. The development of the COVID 19 vaccine was one of the greatest accomplishments of science in recent history. No matter what, this should give people hope for the future. And yet, it is more of a source of division. I hope we can discuss both the inspiring and the difficult ideas in this conversation so that we can do our small part in healing this division. I hope so. Take me through the day of November 8th, 2020, when the Pfizer team were waiting for the results of the phase three clinical trials. We had assembled in a very small office that we are having in Connecticut, very few people. There were five, I think. And in another place, what we call the Data Monitoring Committee, which is a group of experts, independent experts, they're on Pfizer, we're going to have the opportunity to unblind the data and then tell us if the study needs to continue or if it is successful or if it fails. And we were waiting for their call. So the call came a little bit later than what we expected, which created a lot of anxiety to all of us, but came around, I think, two o clock. You're just sitting there waiting? What were you feeling? Sitting there waiting and teasing one another, drinking coffee, making jokes. So how did you feel like when you heard the results, the successful results? Free, liberated, happy. Like if a huge weight that was on my shoulders was lifted. I heard you said, I love you to the team. I did. This is how we speak in Mediterranean. Listen, maybe it's the Russian thing too. I love love, so I appreciate that kind of celebration. So looking back from that moment to before, how much did it cost to develop the Pfizer BioNTech vaccine? What was it like making the decision to make that investment when the risk is very high and you don't know if it's going to be successful? You know, we do a lot of that anyway. This is what we do in our daily work. We are putting money. We are investing in research, which is highly risky. The difference in that case was that we didn't risk at all. We put it all in. We put everything in one go so that we don't lose time. Usually, we will spend 50 millions. And then if that goes well, then we will spend another 50. And then if it goes well, then 100. Here, we put all together a little bit more than $2 billion, $2.3 billion. And it was a significant decision. But it was a very easy decision to make in the context of what we were living at that time. It was a pandemic. People were scared. We were scared. We didn't know how tomorrow would look like. We were living unprecedented situations. And we knew that we have capabilities that may help. So there was not a second question or choice. We go all in. When you make decisions like that, you're the CEO of a company that needs to make money and that hopes to do a lot of good in the world. How much of both of those things are part of the calculation? So when you said it was an obvious choice, I think you've said a bunch of things of the kind of saying we need to go all in, sort of very boldly diving in. How much was that the world is facing uncertainty and fear and potentially destructive pandemic in the early days, just when you're seeing the full uncertainty before us, don't know how it's going to unroll? And how much of it is this may also be a good financial decision to take this risk? Yeah, I think about it all the time. And I know very well that if you focus too much on making money, you will never make. You should focus in what is the real value driver. And the real value driver, it is to make breakthroughs that change patients lives. If you don't do that, you will never make money. If you do that, don't worry. Things will fall into place, and also money will follow. But the mentality of the company is to be how to help the patient. And that's what the management was that the shareholders want, because that's the only way that we can create value. In this particular case, we're not thinking at all about what are we going to make when we sell it or if we don't sell it. Because what we were focusing 100% was how to bring a solution to the world that will help all of us change the fear that was bringing hope to the world. And as always, when you do that, you will have good returns as well. On a philosophical level, on a human level, do you ever worry that the pressure to cover the costs that were invested, to develop a new drug, to develop this vaccine, harms your ability to conduct unbiased studies? Not at all, because the studies are highly regulated. Everybody knows what regulators, and when I say regulators, FDA, European authorities, UK authorities, Israeli authorities, Japanese authorities, Canadian authorities, want to see how the study needs to be conducted and what exactly they need to see to approve it or not. So clearly, everybody takes into consideration how much money I'm going to invest and what is the chances that I'm going to lose them. But what you can do is to change the rules of the game so that you won't lose the money. There are very well established methodologies that would say with very high precision if your medicine is effective, if your medicine is safe. And those are there for all and are playing with the same rules. Do you have an intuition about why is the FDA trying to get 75 years to release the Pfizer data? They're trying to request that it will not be released for 75 years. And then maybe the broader version of that question is do you think people should have sort of full transparency and immediate access to the data, immediate on the scale of weeks, not years? I think the relations with regulators, they have been always very transparent. And there are a lot of laws that they are forcing regulators and companies to put out their interactions and what exactly was discussed. Now, to go into specific details of some discussions, I don't know what is the reason that FDA wants to take the time. And I'm sure they have very good reasons. Well, let me just say my side of it. It doesn't look like a good reason. It looks like maybe it's because I come from the Soviet Union. Now, this is not you saying this. This is me saying this. There seems to be a bureaucracy that gets in the way of transparency. That's always the challenge with government. So government is very good at setting rules and making sure there's oversight of companies and people and so on. But they create, they slow things down, which is a feature and a bug. And in this case, they slow down so much. I think the reason they set it at 75 years is because they set a rate of being able to only review 500 pages of data a day or something like that. And that's a very kind of bureaucratic thing, where in reality, you could just show the data. And it's not like something is being hidden. But in the battle to win people's trust, to inspire them with science, it feels like transparency is one of the most beautiful things, one of the most powerful things that the FDA has. FDA has the potential to be one of the great institutions of our country. And this is one example that it feels, to me, like a failure. So in your perspective, you're saying, I'm sure they have a good reason. So to you, the FDA is this black box that you submit things to once they approve. You know that those are the rules. It's approved. That's it. But this is not a black box. We know very well what is the process. Everybody knows very well what are the processes. The review process also, it is very detailed. They have scientists of very, very high caliber. Not every regulator in the world, but the Europeans, the BRIDs, the FDA clearly, they have very, very high caliber of scientists that they are going into a lot of details. And also, basically everything for a study is really released by law in the specifications of the product, but it's a very detailed document that it is issued and has basically the essence of everything that was discussed. I don't know about specific documents if take them time to release, but clearly this is not a black box type of process. A lot of this stuff is how do you effectively communicate to the world about the incredible science that's been done, about the processes that were followed. I agree with you. And then sometimes it's just in eloquence in communication. It's not that there's a failure process. It's in eloquence of communication and silence. Silence in the moment when clearly a lot of people are bothered and have questions. This is when you speak out and you explain exactly why as opposed to letting the sort of distrust build up and linger because the result is there's a very large percentage of the population that just, I mean, it divides people and science suffers, I think. And also the effectiveness of solutions suffers like the vaccine and so on. I asked a few folks I know if they had challenging questions for you. I'm sure many of them answered your call. Yeah, many friendly folks out there. By the way, I'm sweating not because this is a difficult conversation, it is, but it's also hot in here for the record. So one of the folks is Mr. Jordan Peterson. I don't know if you know who that is. He's a psychologist and intellectual and author. He suggested to me that I raised the concern that there's a close working relationship between Pfizer, FDA, and CDC. So we talked about FDA. Do you worry that this affects both positive and negative Pfizer's chances of getting drugs approved? The fact that there's people that worked at the FDA that now work at Pfizer, Pfizer, FDA, that there's a kind of pipeline. Does this worry you that it affects your ability to do great, unbiased work? I have zero doubts that this is not affecting at all their ability to be unbiased and regulate. And in order to, for the system also reinforces that by creating significant time barriers. If someone moves from an industry to FDA, she won't be able to deal with topics for a period of time. And then for even an enhanced period of time with topics that are related with a company he or she may come from. I think these regulators, they are really very strict. Rightly so. If anything, I feel sometimes that maybe they should be a little bit more open minded, particularly when it comes to new technologies, rather than trying to judge and implement the same framework of variation of new technologies to all. They are always as regulators in the conservative side. But always, always, they are unbiased and they are trying the best. And it's not only one or two people. They have processes to make sure that there are self checks and balances within the agencies, both in CDC and in the FDA. Difficult decisions, they bring external experts that they should express. Easy decisions, they are internal experts that they are debating a lot. And if there are disagreements, they elevate them. So I think we are lucky to have good regulators. I think I agree with what you said before, as with all governmental agencies, there is bureaucracy. And the bureaucracy needs to be addressed. And by saying bureaucracy is not relaxing the bar. The bar needs to remain high. But focusing on what matters rather than on the detail. So you don't, I've been reading quite a bit about history. You don't worry about human nature and corruption that can seep in. You're saying institutionally, there's protections against this. I think there is always the fear of corruption, particularly when you speak about public servants. But clearly the risk is very different country by country. And speaking about agencies by agencies, I think the regulatory agencies have a very good track record in history of the US, of Europe, of England, of very, very good track record of integrity. It's something I think about. So I grew up in the Soviet Union and I need to perhaps introspect this a little bit. But when I was growing up, ethically, there was a sense that bribery is the only way you can get stuff done. That was the system of the time. Like you get pulled over by a police officer. Like obviously you need to bribe them. I mean, it was like the way of life. And then so coming to this country was beautiful to see that the rule of law has so much power. And ultimately the rule of law when enacted, when it holds up, it gives people freedom to do the best work of their lives. But there's still human nature. And that worries me a lot here. And again, it goes back to the perception, the communication, when there's people that have worked at Pfizer and an FDA, at the CDC, you look at their resume, they have those things on their resume, it worries people. Are these great leaders that we are supposed to see as authorities, are they playing a game on us? I would say that I recognize what you said about what happened in, or what, I'm sure that what you described in the country that you're coming from, it was how you experienced it. And I know that there are other countries that you need to do these things to do your job. I don't think it's the case in this country, particularly when it comes to those agencies that you mentioned. I think they have a very high track record. And also, I don't think that there are a lot of people that they are worried about it or doubt it. I'm sure, like everywhere, there will be a minority, but the vast majority of the Americans, the vast majority of the Europeans, the vast majority of the Brits, the vast majority of the Israelis, they trust what FDA or EMA or CDC or MHRA will say. MHRA will say. Still, there's currently a distrust of big pharma in the public. Maybe this is something I'd love to hear your comment on. There's distrust of science when it's tangled up with corporations and government institutions, This is an end with all the caveats that the numbers are small, no one died. It was 100% efficacy on deaths. Of course, I'm sure that in real world, when the numbers are getting very high, we may have 99 instead of 100. But these are spectacular results for something that you can take home and stay home. The biggest problem right now in Europe, in the US, when we have surges, every time that we have a surge of COVID, it is that the ICUs are full, the hospitals are paralyzed, they have to postpone elective surgeries, they have to postpone other operations because they don't have the capacity because of that. Keeping people out of the hospitals, home, keeping people without dying, it is something that I didn't have before. And this is a significant, significant game changer. I have to ask a controversial, difficult question. What are your thoughts about ivermectin? Has it sufficiently been studied? Has Pfizer considered it in its, like I said, incredible development of the antiviral as a comparator or that kind of thing? Just investigate it in general. The reason I bring it up, because I've read quite a few criticisms of people. There's been some comparisons of paxilovir to the ivermectin, and I think people should look up. There is Dr. John Campbell that describes that comparison and makes that claim, and there's quite a lot of people that debunk or argue against that. You can do your own research, but there is a lot of people that kind of see this free drug without patents on it and say this could be the savior. So can you just speak to that comparison? It's not the first time. If you remember, there were other compounds that were claimed that they are the solution to COVID, and clearly they were proving that they're not. There are compounds that are solutions and compounds that are not. I, as a scientist, and I discuss with our scientists, they don't see any reason why a medicine like ivermectin, which is a parasitic site, to be able to act on COVID, and so they don't see that there's any connection, and they haven't seen any paper that describes someone that used it that had any results. I'm sure that there will be some people that will claim, because people are claiming anything, but I don't think that there was any paper in any peer review magazine, any reliable scientific magazine, to support this claim. So we are focusing on saving people's lives. We are not focusing on craziness. Well, to push back, there is quite a lot of papers, but the studies are small, so there's no conclusive evidence, and that's the point. I haven't seen any that it is reliable. I don't know where are these, small or big, reliable. I haven't seen any. Well, some of the big ones have been retracted, which means they weren't legitimate. Yes. Yeah, so? This is definitely something that people need to look into, the people that kind of question are the effectiveness of ivermectin, definitely something to think about, and I think it's the reason that past public. It was chloroquine alone before. Yes. For God's sake. That's why PaxLovid. How many people died because of that? Yeah, this is the dangerous thing. This is the sad thing. PaxLovid has been studying thousands of people and will be under the scrutiny, not only of regulators, but as we will go into the implementation, as it happened in many countries, they will monitor to see what's happened. Let's say that whatever we do, once it is out there, within a few weeks, they will know all hospitals, if it works or not, because they will see the statistics. We've gone through one of the more difficult periods in recent human history over the past two years, like as a society. What gives you hope about the future for our human civilization? You look into the next few years. I think the human ingenuity. I think although there is, the world always is progressing, although there are a lot of things that need to be fixed in the society of 2020. The society of 2020 is better at large than things 50 years back, 100 years back, in all different aspects, from poverty, for human rights, from science, from quality of life, from any aspect. I am positive that humans can create and always create a better future and will continue doing so. You have helped save the lives of millions of people, helped improve the quality of their lives, but you yourself are just one biological organism with an expiration date. Do you ponder your mortality? Do you think about your death? Are you afraid of death? That's a very interesting question. I was discussing with a lot of people that I was fearless of death, I couldn't care less, when I was young. The first time that I start feeling that I want to be around was when I had kids. And then I started feeling that, oh gosh, I hope I will be around to see their wedding. I hope they will be around to see their children. So if there is something that scares me, the possibility I will not be part of their lives anymore and I will not be watching. I hope there is life upstairs, so I will be able to watch them from there. From upstairs, get a nice overview. Let me ask the big ridiculous question. And you only have two minutes or less to answer it. What is the meaning of life? What's the meaning of this whole thing? You said ingenuity is the thing that gives you hope. We seem to be all busy trying to help each other, trying to build a better world. Why are we doing that? I would repeat something that Steve Jobs has said. Death is life's biggest invention. It eliminates the old and gives place to the new. Life is all about moving forward. Life is all about creating new things. And maybe everyone is a contributor, but no one is the owner. And always creating something new. Always. Adding something beautiful into the world, maybe a little bit of love. Hopefully. Albert, thank you so much. It's a huge honor that you go through some of these difficult questions with me today and that you give your extremely valuable time for this conversation. Thank you so much for talking today. Thank you for your interest and I'm happy, as I was telling you before, but I can brag with my kids that I was in your podcast because you are their hero. You made it. I made it. Thank you. Thank you. Thanks for listening to this conversation with Albert Burla. To support this podcast, please check out our sponsors in the description. And now, let me leave you with some words from Oscar Wilde. The truth is rarely pure and never simple. Thank you for listening and hope to see you next time. like we've talked about. But they have to be entangled to achieve scale, oversight, and to achieve the kind of scale that Pfizer's been able to accomplish. So, how can Pfizer regain the public trust? How can you regain the public trust, do you think? Not regain, but sort of take steps to increase the public trust. Reputation is something that you can lose in buckets, but you can earn it back in drops. And once you've lost it, you are going to take a lot of effort to bring it back. And the pharmaceutical industry lost it. It's clear that the reputation of the industry in the last decade was on the lowest that we have seen ever. And there are many reasons for that, but clearly there are reasons that are related also with the behavior of the industry. That needed to change, and I'm hopeful that very few will disagree that the industry is a very different industry right now. That being said, I truly believe that if there is one lesson that stands out from the many lessons that we learned during COVID, is the power of science in the hands of the private sector. I think it was the private sector that came with solutions with diagnostic tests when we didn't have, solutions with respirators when we didn't have, solutions with treatments, solutions with vaccines. And I think that demonstrated very clearly to the world the value of thriving life sciences sector, private life sciences sector to society. That also affected very positively the reputation, both of the sector and of Pfizer. I'm not going to make the mistake to consider given. I'm not going to make the mistake that because our reputation is high, that will remain so. We need to earn it every day. Every day with everything we do, with everything we say, with the way we behave. And I hope that we'll rise to this occasion and we will do that. You've been at Pfizer for 28 years. Time flies when you're having fun. And you've become CEO in 2019. It is a company you love, a company you believe in. It's a company that has developed drugs that has helped millions of people. So let me ask yet another hard question on this topic of reputation. In 2009, Pfizer pleaded guilty to the illegal marketing of arthritis drug Bextra and agreed to a $2.3 billion settlement. How do you make sense of the fact that this happened to a company you love and that you believe in? Yes, the Bextra case in 2009 was related to things that happened in 2003. And the things that happened in 2003 were things that basically several of our reps did off label promotion. So they spoke with the physicians about off label use of the product, and they shouldn't. Can you clarify it? So off label are things that the FDA didn't approve, extra stuff. You basically say this drug does extra stuff that the FDA never approved. Correct, and this is something that it is allowed when physicians are speaking to physicians, but it is not allowed for the pharmaceutical companies to refer to these studies, because usually our studies that are happening off label. And apparently several of our reps in 2003, they did it. And we had to settle in 2009, and we paid a very big fine, as you said. The fine was related not to the severity of the conduct, but the size of the revenues. So the fines are, if Bextra was a small product, we would get a small fine. Bextra was a very big product, and we got a very large fine. Very bad, what happened in 2003. I don't think that these things happened since then. We have a stellar record from 2009 until now of complying with every single regulation and rule. We have internal processes to make sure that these are not happening by individuals that may have an interest. For example, to get a promotion, they may try and do things that are not the right things. And we have, more importantly, a culture in this company that really sets aside people that they think differently. So I didn't like what happened in 2003, but I believe a lot has changed in the 20 years that followed, or almost 20 years. So you're developing drugs, you're developing solutions to help millions of people, but there's risk involved. And so there will be lawsuits heading back your way because there's a lot of lawyers in the world, partially. How do you put that into the calculation of how you try to do good in the world? That some of the cost is the lawsuits. How do you not fall victim to thinking that it's just the cost of doing business, and that some of the lawsuits might actually represent real pain that people are going through? No, I think that we try always to do the right thing. And that's, as I said, very well embedded into our culture. If you don't do the right thing, sooner or later, you will pay for it, one way or another. And right now, for us doing the right thing, it is being able to find innovations to issues that are real, diseases that they do not have good coverage, good treatments right now. We try to find treatments that significantly surpass the current standards of care. And we try not only to comply with what regulators are asking us to do, this is what you need to do to prove the safety or the efficacy, but exceed them. No matter what we do on that, I'm sure that people will find opportunity because, as you said, there are a lot of lawyers to sue us. But we believe in the justice system and we believe that eventually, if you are doing the right thing, you will be on the right side of the history. I'm really glad you say that because focusing on doing the right thing, no matter the money, I believe is the best way to make money. That's exactly what I said. And also, in another way, in other realms, creating a product that people love is the best way to make money. So focusing on the core of the thing that makes people feel good, that brings value to people's lives. So I'm now in Austin, Texas. My good friend, Joe Rogan, he's been highlighting to me this aggressive marketing on mainstream media channels by Pfizer. So let me ask a general marketing question. Do you see this as a conflict of interest? Is it my bias, the reporting of news? That a lot of us, a lot of people, me included, look to these mainstream channels of news for kind of authority of like, what the heck's going on in the world? And if Pfizer is sponsoring many of these shows, there's a worry, it may be a perception thing, but there's also a natural worry that it would influence what they're talking about because they're afraid of losing the sponsorship. It's subtle, but at scale, it might have a serious impact. Do you worry about this? I think people could go one way or another because of multiple reasons. From our perspective, I don't think we have aggressive marketing. What we do, we go on TV and we are having ads about our products and they're highly regulated. I think it is the right of people to know, to learn that if there is a product like that. It's very clearly that we cannot say things that they are off label, that have not been approved. We need to have, every time we go on TV, as you know, FDA is forcing us to say also the bad things that can happen for a medicine. Sometimes that takes more time than the good things. And I don't think that we are doing aggressive marketing. Now, people could be influenced and can be biased in the podcasts or the other type of media activities that they have for multiple different reasons. Yeah, I know, but it's still, it's pressure. It's human nature. I mean, one of it is perception, but I worry about too. I think I have a ton of sponsors for this podcast, for example, and none of them ever asked me to anything. They're just, you know, I think likely that kind of pressure's not happening for Pfizer, but there's implied pressure sometimes. And I worry about that a lot because, you know, I look at academia, like I look for the good in people. I tend to believe most people are good or have the capacity to be good and desire to be good. When I came to MIT, I was a little bit disappointed, maybe heartbroken. How much pressure? I think unjustified pressure people felt from financial constraints, especially at MIT when there's, I think, a lot of money. People still felt constraints and they weren't, it wasn't bringing out the best in them. They weren't supporting each other. They weren't loving each other, like celebrating each other's successes. I don't want to blame money on everything, money constraints, but when you have sponsors, it just, I personally worry that it doesn't bring the best out of people. And so I feel like I want to put some responsibility on sponsors and great big companies like Pfizer to kind of not get in the way of the best of human nature, whether it's sponsoring podcasts, mainstream media, like, I don't know, athletes, whatever. You need to know that we are so, so careful with sponsorships. First of all, we have very few, very, very few. We have a team that for every single one, could be $2,000. They will try to see if there is a conflict of interest in the way we do it. And also what is the reputation of the persons or the programs that we are sponsoring? So I don't think, our friend, I think was from Texas. Yes. Yeah. I don't. Joe Rogan, yes. Yes. I don't think he got it right that we do those type of things. We don't. Oh, in terms of like having a negative effect on. Not even having aggressive sponsorships. We have very few. Yeah, when you clip them all together. And most of the sponsorships that we have, it is more on patient related organizations rather than we are very careful not to sponsor other things that can be perceived, not even influenced, but perceived that we may influence. So we are very, very careful on that. This is not the case with us. So with the incredibly fast development of the vaccine, could you tell me the story from the engineering to the science, to the human story of how you could do it so fast? By November, you even had the ambition to do it by October. It was in the initial days. How do you. Eight days later. In that time, how do you show that the vaccine is safe and effective given that I think previous vaccines have taken years to do that? Yeah, the vaccines take years to do that. And the time that it takes, it is basically the vast majority of the time to conduct the final phase three study, that is the confirmatory study. And you do that because the phase three study costs a lot of money, in our case, cost almost a billion. So you don't want to go and risk a billion in blinded data normally before you do a lot of experiments to make sure that the product that you're putting in the phase three is the right one. We didn't have that time. So we risked all the money. So we went into, we condensed all the time towards this phase three. But the phase three study had to follow all the rules that any study follows when we do this trial. Could you just briefly describe the basics of what is phase one, what is phase two, what is phase three? Let's say that there are so many phases when you try first of all to find what is the right vaccine. We tried from 20 different vaccines, we nailed down to four. And for those four, we selected eventually two and then eventually one. Once you have those selections, what is the dose you're going to use? And then we tried multiple different doses to see which one we think is the best. What does trying entail in those early days? You go first of all with smaller doses in humans. And then after you have done a lot of experiments in animals so that you can feel that it is safe enough to go to humans and then go with very low dose. And then you gradually increase the dose and then you monitor those humans to make sure that there are not any, let's say reactogenicity to what you are giving them. At the same time, you start to measure what it's doing in terms of immune responses. So you do that with multiple vaccines and you do that with multiple doses and you do that with multiple ages of people, young people, old people. And eventually from the 20 vaccines to multiple doses, to multiple schedules, is it after three weeks the second dose or is it after four weeks or after six months? All of that will inform you that I think this is the vaccine, this is the dose, this is the scheme that I believe will give me the best results. And when you have that, then you go to do what we call the phase three. This is a very big study with thousands of people where you use the vaccine that you think is the right one and a placebo. The placebo and the vaccine, they look identical. Nobody knows if is injected a placebo or a vaccine. The physician that makes the injection, the doctor doesn't know if he's injecting placebo or vaccine, he knows a barcode. Only the computer knows. In order to go into this computer, there are keys and there are at least two people that needs to put their keys so that someone can see the data. And those people, they have legal obligations never to do that, right? So before a certain point. So all of that is blind. The idea is that when you go into this study, you need to make sure that you are going with the right one. That's why it takes so much time. But the study is the study. You need to have a significant number of people that will give the two and then you let them live their lives. And then you see how many of them will get the disease. And then you see if there are differences in percentage of infections for the vaccinated compared to the non vaccinated. At the same time, you're monitoring all of them to see if there are differences in the safety profile. If those that go to placebo have the same, let's say, heart attacks with those that they didn't. They got the vaccine because heart attacks will happen if you have 50,000 people because it's part of life. These are the, all these processes are very, very, very well established and since years. What we did the last one was exactly the same as we did always. We just didn't lose time. We didn't, we're not careful with money. Instead of recruiting 50,000 people over a year, because we had let's say 30 hospitals doing the recruitment, we went with 150 hospitals doing the recruitment. That cost a lot of money. But instead of recruiting them in a year, we recruited them in three, four months. So I did this type of things by taking return on investment, taking costs out of the equation and we were able to achieve this result. But it's not the process, believe me. It is the heart of the people. People don't know what they can and what they cannot do. And if anything, they have a serious tendency to underestimate what they can do. And always, when you ask them something that is seemingly impossible, they will think out of the box to be able to deliver. We discussed about the timing. Instead of eight years, we then asked them to do it in six, we asked them to do it in eight months. Our normal manufacturing yearly production of Pfizer was 200 million doses of vaccines every year. That's what we are doing in the last 10 years. We didn't ask them to make 300 million doses for a new vaccine. We asked them to make 3 billion doses for a new vaccine. The discovery phase of a new molecule, like the treatment that we have now, the pill against COVID, takes four years. We didn't ask them to do it in three. We asked them to do it in four months, which is what they did. When you are setting this type of goals, they know immediately, they cannot just think within the box. And immediately, this is where the human ingenuity and the heart comes. And this is how they surprised all of us. So there's incredible science and engineering going on here. This is an incredible thing. Absolutely. This is what's bothering me, that the conversation in public is often not about that. It's about politics, unfortunately. Politics. So I spent the day with Elon Musk yesterday. He works with rockets. Similar situation as with Pfizer, in the sense that there's NASA and then there's this private company. And that's a source of incredible inspiration to people. No politics, very little politics. So this is part of the thing I'm trying to, I'm hoping to do our little part in this conversation to help untangle a little bit, just reveal the beauty and the power of the thing that was done here, especially with the vaccine, but other things that are being done with the antiviral drug. Let me just kind of linger on the safety. What can you say? There's a lot of people that are concerned that the Pfizer vaccine, by the way, of which I took two shots, no booster yet, is unsafe. What do you say to people that say that? No, they should not fear something like that. It's completely wrong. There is no medical product in the history of humanity that have been tested as much as this vaccine. Has been administered to hundreds of millions of people. And because of the importance of COVID, they have been scrutinized, those people, constantly. Right now, healthcare authorities are looking for every single signal around the world of people that they got the vaccine and try to see if it is vaccine related or not. There are electronic medical records that will tell us when and what happened to a person when he did got the vaccine. And we know now, we have so high certainty that it is so safe, exactly as the data sheet says about this vaccine, more than any other product. They should not be afraid of something like that. And they should not listen to information that it is misinformation, that it is spread on purpose. Well, I don't like the word misinformation because, you know, again, back to the Soviet Union, anyone who opposes the state is spreading misinformation. So you can basically call anything misinformation. That's the unfortunate times we live in, is you can call anyone, you can basically call anybody a liar and say, I'm the sole possessor of the truth. And just no offense to me, just because you wear a tie, it doesn't mean you're any more likely to be in the possession of the truth than anyone else. So. I wouldn't disagree with that at all. I don't think that. That's somebody who's not wearing a tie. And as you can, people can see that I'm not wearing a tie and you are. But it's not about being able, those that they have the power to impose on the others, the stigma that what you're saying is misinformation. But there are a few things that as society we have accomplished and science is one of them. And data is, and analytics of data is another one. And to say that something which is highly scientific by people that they are not scientists. I think that it is not what you're describing, what used to happen in Soviet Union or in any other autocratic regime in the world right now. But I definitely do think that the scientists, the public science communicators I've listened to over COVID have really disappointed me because they have not spoken with empathy. They haven't sufficiently in my view have put their ego aside and really listened to people. Yes, people that don't have a PhD, people who have not really, maybe not even taken like a biology course in college or something like that. But still they have children, they worry, they fear. They don't know who to trust. They don't know if they should listen to the CEO of Pfizer who might have other incentives in mind, who might just care about money and nothing else. And so they just use common sense and they ask questions. And I think to them talking down to them as if they're not intelligent and so on is something scientists have done almost like rolled their eyes. And that disappoints me because I think that's kind of what is the source of division. Humility is a virtue. Yes. And the fact that you are educated doesn't mean that you are having either humility or empathy or you have good human qualities. This was never and will never be a metric of judging this type of virtues. Those that they do this, they're wrong. And actually they are not doing good service to the public health because they're undermining. People are not stupid. They see if you're not be respecting them and if you're not respecting their need to learn because that affects their health, the health of the mother, of the kids. So I fully agree with you that we should be very patient to explain again and again and again what is happening. And the vast majority of the people that they don't get vaccinations right now is because they're afraid. It's not for any other reason. It's not that they have an agenda. What I'm saying it is there is a small number of people that they have made business for them to profit from this anxiety. I'll give you an example. I have been arrested by FBI. This is what someone wrote. I read it, I laughed. I mean, okay, this is where they take it. There was a reason why they wrote it that. The Pfizer CEO was arrested by the FBI because they want to create doubts in the minds of the people that they're afraid and say, look, if the FBI arrested him, likely I will not do the vaccine. But I laughed. A week later, the wife of the Pfizer CEO died. There is a picture in this website of my wife. Someone sends to me, now I'm pissed. I'm not laughing. I tried to find my kids to tell them, if you read something, mom is fine. Don't worry. Then I remember that she has very old parents back in Greece. We start calling them to making sure because so you know that that will be picked up by Greek newspapers and they will publish it, okay? They are those people that wrote these things. They know very well that my wife didn't die and died because she was vaccinated, right? So this is the narratives that they are on purpose forming to profit from the stress and the anxiety of good people. And that's something I have to kind of, people that listen to this, that kind of doubt institutions, I do also want to say that there's quite a few folks who realize they can make money from saying, the man is lying to you. The government is lying to you. It's all corrupt. It's all a scam. Big pharma is lying to you. They're manipulating you. I'm surprised at how much money can be made with that. And it's sad. So you have to, just as people use their common sense to be skeptical when listening to politicians and powerful figures, they should be skeptical to also when listening to sort of the conspiracy theorists or not even the conspiracy theorists, but people who raise questions about institutions. Think on your own, think critically with an open mind that everyone can be manipulating you, but also everybody has the capacity to do good. And I think science in its pure form, not when entangled with institutions is a beautiful thing. And in the hands of many companies, it is a beautiful thing at scale. Still, you have a lot of incentive as having created the vaccine at Pfizer, this incredible technology to sing it praises. So there's a kind of, you know, people are skeptical, like how much do we trust, how excited Albert is about this vaccine. So for example, I mean, not to do a Shakespearean analysis of your Twitter, but I think he tweeted something about a study with a 100% efficacy of the vaccine or in stopping and transmission or something like that. Do you regret sort of being like over representing the effectiveness of the vaccine, technically saying correct things, but just kind of like highlighting the super positive things that may be misinterpreted, you know, saying 100%? No, I never said something 100%. Every time I speak, if a number is 100%, I rush to say that in biology, there is nothing 100% because always there will be when you go to the millions, okay? There were in the study things that were 100%, for example, deaths or in South Africa. When we tried, there was 100% efficacy. Clearly, it's more numbers. When the numbers will become much bigger, the 100% will not hold, but will be 95, 96. So still the direction of this is the point. So I'm very, very careful what I tweet. And in addition to how careful I am, I have people that they are looking at and they're having second or third opinions to make sure that we don't put, why? Because I know that people are listening to me right now, everything I say, and I want to make sure that they continue not only being clear as to what I want to say, so there are no misunderstandings, but also I maintain the trust of the people. I don't think that someone who only cherry picks information and only emphasizes positive things, it's someone that is the one to be trusted. And I want me and Pfizer to be trusted. So many felt the vaccine was presented as a cure that wouldn't require regular booster shots. Was that something you believed early on? Did you always believe that many regular shots would be required? And maybe in a bigger picture, how many do you think this will, for the Pfizer vaccine, is it something you see that's taking a booster shot regularly, like annually? Yes, in the beginning when we had the first months with the vaccine, people would ask me, do we need another one? And I said, we don't know. I was very clear about it. Then around April, May, I start seeing the first data and I made statements that I think we will need a booster around eight to 12 months after the second dose. And then after that, annually vaccinations, this is what I said, believe is one of the most likely scenarios. And it was based on the data that I had, but then Delta came. And because I always making the caveat that with absent a new variant with everything we know. With Delta, it was proven that we need the booster to move to the three, to the six months. And this is what happened. And I still said, I think the booster is a six months. And then I think it will be an annual revaccination likely. We have to monitor to see the data, but this is the likely scenario. Now we have Omicron. And Omicron says that two doses might be challenging. We don't know exactly yet, but three doses work. So clearly a lot of countries already started moving now the third dose, not from six months to three. So that they will reduce the period that people will not be protected with the third dose. I don't know with Omicron if how long this will last. And frankly, I don't know if we will need a new vaccine tailor made to Omicron based on everything we know so far. We are monitoring and we will know way more in the weeks to come. If there is a need for a new vaccine, we will have it. And if there is a need for mass production of this new vaccine, I can also feel very comfortable that we will not lose any of our capacity that we have developed. Right now we are running at 1 billion almost approximately doses per quarter, four per year. And if we have to switch and have half of that in the new, half of that in the old, we will do still 4 billion doses. So I think the world should feel very, very comfortable that if there is a need, we will be ahead of the virus. Yeah, you did, you delivered or produced 3 billion this year vaccines and you're on track to do 4 billion next year. I mean, if we had a lot more time, we would talk about how the heck you achieve that kind of scale, it's truly incredible. Let me ask the policy question. What are your feelings about vaccine mandates in terms of, do you think the most effective way to vaccinate the population is to acquire it? Or do you go with the American way and give people the freedom to choose? I think it is a very difficult topic and a very difficult decision for whoever needs to make it. And clearly it's not me. It is the public health officials of every country that they have to make this decision. I have to make the decision for Pfizer employees. And I had to balance the fear of those that they work, that they want to feel that the others are vaccinated and the fear of those that they don't want to get the vaccine. And eventually I came to the decision that we will mandate it at Pfizer. We are flexible, we are giving exceptions, of course for health, maybe some religions, but we decided to mandate it. Now, at Pfizer, when we did this decision, we were at 90% vaccination rates when we said we are going to mandate it. And that took it up to 96. It works, right? This 10% was never going to move, I felt. Because no matter what, you have a small number of people that really are scared. And they don't feel comfortable to do it, okay? It worked in our case, we took it to 96%. I'm happy for those people. A lot will not disease and some will not die of those people. But it's not me to say, because the debate, it's serious debate. And there are a lot of pros and cons if you need to push people, if you need to give them the freedom. And it comes with the territory. If you are elected to run a country, you should be ready to make difficult decisions. And no matter what decision you make, there will be fake stories written about you as we talked about. You will not be able to please everyone. Yes. Well, let me just say that I think, again, coming from the Soviet Union, I think at the public level, at the federal level, mandates is a really bad idea. Even if it's good for the health of the populace, there's something about preserving the freedom is really powerful about this country. Like doing the hard work of convincing people to get vaccinated, to choose to get vaccinated if they want, but still have the freedom not to. That's a really powerful freedom. To me, it's super lazy to mandate. People should understand the science and want to get vaccinated. Do you think children need to get vaccinated? I do. I do think that they need to get vaccinated. So age ranges five to 16. There's a lot of parents that fear for the wellbeing of their children. Can you empathize with those parents? Can you steel man their arguments against the vaccine for their children? You know, because people know who I am. I had the opportunity to interact with parents before that was, let's say, approved. And there were so many, way more, that I had a lot of empathy because they were afraid for their kids because they didn't have a vaccine. And they were the ones that were speaking at that time. Bring me vaccine. When are you going to bring me a vaccine? I really fear. I feel that this is unfair, but I am protected. My husband is protected. My old son is protected. And my little sweetheart, because she's below the age, is not protected. Now that we have the vaccines, I'm sure that those that they are afraid of the vaccine, not of the disease, which are smaller number, admittedly. Also, they will have, if they're afraid of them, I'm sure that they will afraid even more about their kids because they love, I would say, more than they love themselves. So it's going to be this situation. And again, the same. How can you do to demonstrate, to convince people, to win the minds and the hearts of the people that this is the right thing to do? What do you think about that calculation? Because the risk for kids is very low. Kids do die. Kids do go to the hospital from COVID. Yes. But the rate is very low. The rate is lower, but kids, they do die. And how can you say that I'm not going to, I'm not going to protect a kid for something that it is likely to happen? And it is not only that. What happens in the school when they stop the education process because a kid got the disease and they don't have vaccines so that they can control. It is such a big disruption and such a big risk for the health of the kids that it shouldn't be a debate. Look, how many kids are having polio right now? Way fewer number than those that they're having COVID in the hospital. But everybody's getting the vaccine. Well, polio was deadlier for kids. But it's not now. So why a kid to do it now? Because it needs to be protected. Well, the unique thing about the COVID vaccine is a new type of technology too. So there's an extra concern. Choosing to vaccinate a child, you're making a choice that can potentially hurt them. That's the way parents that are hesitant about the vaccine think. I think choosing to vaccinate children makes a choice so that something could not potentially hurt them, which is the disease. That's why we are doing vaccinations since ever. I know that there are people that they're concerned for themselves and for their kids. What I know it is that I'm a scientist and I'm a parent. And I am telling you that vaccines is a very good thing for kids. And thank God we were able to develop. So we've talked quite a bit about the vaccine, but there's an incredible new technology that Pfizer is developing with the PaxLovid antiviral for COVID. Where does that stand? How does that work? And how are you able to develop it in four months? Like you said, and all of that in just a few minutes. First of all, what this is about, this is a real game changer. This is a course of treatment that you get only if you get the disease, you get COVID. Then what happens is that you will take for five days, pills day and night, and twice a day for five days. And instead of 10 people from those that disease to go to hospital, only one will go.

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