第 238 期·中文精讀

弗朗西斯·柯林斯:美國國家衛生研究院(NIH)

Francis Collins: National Institutes of Health (NIH)

NIH 院長談基因科學、機構如何資助醫學研究,以及公共衛生決策中的科學與信仰。

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中文精讀由 AI 基於原始訪談改寫,非官方翻譯,可能存在偏差或錯誤;表述以原音訊與官方文稿為準。說明

一位被三位總統任命過、掌管 27 個研究所和中心、領導過人類基因組計劃的人,在被問到新冠是否可能從實驗室洩漏時,給出的回答是:“我不能排除這個可能。”

說這話的是弗朗西斯·柯林斯(Francis Collins),美國國家衛生研究院(NIH)院長。他緊接著補了一句,他認為這相當不可能。但前半句已經足夠說明問題:在這類問題上,最不該做的事就是假裝確定性存在。

這場對話發生在 2021 年 11 月。柯林斯已經宣佈年底卸任,結束 12 年的院長任期。訪談從他最不願意談的地方開始,實驗室洩漏、功能增益、福奇被圍攻,一路走到人類基因組、大腦圖譜、上帝與死亡。中途有大量讓人不舒服的細節,也有幾個難得的亮光時刻。

從最難的問題開始:實驗室洩漏

柯林斯的立場很清晰。他認為最可能的路徑仍然是自然起源:病毒從蝙蝠出發,可能經過某個尚未被識別出來的中間宿主,最終進入人體。他以 SARS 和 MERS 作為對照。SARS 用了 14 年才確定果子狸是中間宿主,MERS 快一些,找到了駱駝。

新冠的溯源調查遠沒有到這個深度。中美的政治氣氛讓一切變得更糟。他的原話是:如果現在有人在調查,我們也不會被告知。

這裡面有一個容易被忽略的時間尺度問題。公眾期待的是幾個月內給出答案,而病毒溯源在歷史上是以十年為單位推進的工作。這兩種節奏之間的落差,本身就成了陰謀論的溫床。

柯林斯反覆提到巴斯德那句話,科學不分國界。他自己的整個職業生涯都建立在這個前提上。人類基因組計劃是 6 個國家、2400 名科學家協作的產物,資料全部公開,沒人在乎署名順序。中國也參與了,那是中國第一次真正進入大科學專案,而且完成了自己的份額。

他說,現在完全不一樣了。

一個被用爛的詞

功能增益(gain of function)這個詞,柯林斯花了很長時間去拆解。他認為這個詞已經造成了嚴重的混亂,因為它在科學裡有兩種完全不同的用法。

廣義上,功能增益是無處不在的。NIH 的臨床中心正在做的 CAR-T 類試驗,把病人的免疫細胞取出來,用基因療法增強它們識別癌細胞的能力,再輸回體內。柯林斯形容這些細胞是“小忍者戰士”。這就是功能增益,而且它可能救命。他舉了個更日常的例子,自己戴的眼鏡也是一種功能增益,否則他看不清對面的人。

真正受到嚴格監管的是另一種情況:研究物件是已知能引發大流行的人類病原體,而實驗在增強或者可能增強它的傳播力和致病性。這類實驗有個專門的名字,EPPP,即具有大流行潛力的增強型病原體。判斷標準由國家生物安全科學顧問委員會花了三年時間制定,審查小組的成員遠遠超出 NIH 的範圍。

這個門檻極高。過去三四年裡,只有三項實驗獲批,全部是流感病毒。

武漢病毒所那批實驗到底算不算

這是整場對話裡最技術、也最關鍵的一段。

柯林斯說得很直白:武漢病毒所那些由紐約生態健康聯盟(EcoHealth)轉包、用 NIH 經費支援的實驗,不符合 EPPP 的標準。

關鍵在研究物件。EPPP 只適用於已知能感染人類、具有大流行潛力的病原體。那些實驗用的全是野外分離的蝙蝠病毒,從未被證明能感染人。

具體操作是把四種不同蝙蝠病毒的刺突蛋白基因互相調換,看哪一種能更好地結合 ACE2 受體。這個操作在科學上屬於常規手段,但沒有跨過那道門檻。

他特別強調了一點:那些蝙蝠病毒與 SARS-CoV-2 的基因組相似度只有約 80%,在進化尺度上相差幾十年。任何把它們說成新冠源頭的人,都是在做可以被證偽的斷言。他用了一個詞,“不負責任”。

不過他也承認有一處程式問題。受資助機構沒有按規定上報一項實驗結果,那項實驗裡病毒載量略有上升。這是管理疏漏,但性質與“製造了一場大流行”完全不同。

灰色地帶該由誰來劃線

訪談在這裡出現了真正的分歧,而且分歧點很微妙。

柯林斯說他樂於討論灰色地帶,他不舒服的是另一件事:有人根據自己的政治立場,自行重新定義那條線在哪裡。門檻是三年審議的產物,所有人都同意過。如果這個門檻需要重新考慮,可以重新考慮,但不能拿一個已經做完的實驗,回頭宣佈門檻不是當初那個門檻。

對話的另一方提出了一個更根本的質疑。實驗的風險在於,你可能做出自己沒預料到的結果。這正是灰色地帶的本質。而公眾有權知道這種不確定性。

柯林斯接受了這個前提,並且給出了一個具體承諾:2020 年 1 月,也就是疫情改變一切之前,NIH 已經要求同一個顧問委員會重新開會,審視現行框架是否合適。疫情來了,委員們都是傳染病專家,說自己沒時間。他認為現在是重啟這件事的時機,而且這場討論應該儘可能公開。

他還說了一句很重要的話:如果公開討論的結論是這類實驗在任何情況下都不該做,那就是結論。

他在這段裡的姿態,和他處理其他問題的風格不太一樣。他沒有把“我們已經有嚴格監管”當成終點,而是把它當成一個隨時可以被推翻的臨時共識。這個姿態在科學官僚裡並不常見。

如果一百年後有人在地下室造病毒

話題被推到最遠的地方。隨著合成生物學成本下降,功能增益類的操作會越來越容易。目前最嚴格的監管只覆蓋聯邦資助的研究。沒有任何理由認為這類活動會止步於此。

柯林斯承認這是真實的風險。但他給出了一個有意思的反駁:生物武器很難做到只殺敵人不殺自己。人類在基因層面的相似度太高了。所以要發動這樣的攻擊,需要的是一個相當瘋狂的團體。

他不認為這是迫在眉睫的威脅,但他認為必須持續關注。已經有一些機制在運轉。比如有人向主流供應商訂購一段寡核苷酸,如果序列恰好匹配天花病毒,他會被發現。

問題在於這類追蹤在國際層面還很弱。他把它歸入一個更大的困境:當涉及倫理問題時,這個世界缺少決定什麼可以做、並且真正能執行的機制。他舉了人類生殖系基因編輯的例子,除了道德呼籲和各國自行其是,沒有更強的約束。

對話裡提到了一個更日常的擔憂:惡意之外,還有無能。說話者的父親是物理學家,在切爾諾貝利工作過。那場事故沒有陰謀,是一連串官僚系統的失誤疊加。

柯林斯沒有迴避。SARS 冠狀病毒在中國實驗室洩漏過兩三次,有人因此死亡,幸運的是很快被控制住了。他的結論是:你必須在研究病毒和防止洩漏之間同時下注,不能只做前者。BSL-2、3、4 的分級體系必須被嚴格執行,同時你必須承認,你無法指望每一個人在任何時刻都完全按規程操作。這個機率也要算進風險收益的賬裡。

福奇被圍攻這件事

柯林斯是福奇的直接上級。他的態度沒有任何模糊空間。

把託尼·福奇這樣一位把畢生精力投入傳染病防治的人,因為政治原因變成攻擊目標,某些人試圖藉此轉移對自己失職的注意力。這從來就不該發生。(弗朗西斯·柯林斯)

他提到了那個邏輯閉環:先決定不喜歡某個人,然後編造材料,再曲解他關於功能增益的發言,最後說他在國會作偽證。他說這根本不是事實。

關於“反覆橫跳”的指責,他的回應是:科學變了。德爾塔變異株改變了一切。你當然不希望他今天還說去年那套話,那才是錯的。

訪談在這裡遇到一個更難的追問。福奇作為科學家完成了職責,但作為科學的臉面,他是否也負有爭取信任的責任?當大量民眾不信任他時,是否也該由他來修復?

柯林斯的回答是:給人信任最好的方式就是告訴他們真相。他不認為福奇多表達一些謙卑會改變什麼,因為攻擊者需要的是一個靶子,用來分散人們對自己政黨失職的注意力。他甚至推測,如果福奇退出、自己站到那個位置,遭到的攻擊會同樣猛烈,只是因為他曝光度低才倖免。

對話繼續往下壓。有人提出,如果福奇公開承認早期不建議戴口罩是基於當時最優資料的判斷,而後來發現這個判斷錯了,這種謙卑的表態可能會贏回很多人。

柯林斯的回應裡帶著一種疲憊。他說自己看到的分裂之深、之暗,超出了他原本的估計。

他解釋了口罩建議變化的兩個真實原因:一是口罩短缺,醫院急需;二是早期沒有意識到無症狀感染者能高效傳播。資料變了,建議就變了。這是基於當時資訊的判斷,談不上錯誤。但這一點無論解釋多少次,都攔不住“他反覆橫跳”這句話被反覆使用。

在恐慌與真相之間做減法

這裡有一個關於科學傳播的核心困境。

作為科學家,本能是傾倒全部資訊:已知什麼、未知什麼、還需要做什麼實驗。柯林斯說,這種輸出方式在晚間新聞的十秒片段裡基本沒用。你必須把它壓縮成一個建議,一個在當時資訊條件下你能給出的最好的建議。

而且這個建議還要考慮另一層:每一句話都可能引發恐慌。口罩短缺的時候,說實話可能導致醫護人員沒有口罩可用,也可能導致全民搶購。

這類計算沒有標準答案。一百年前關於口罩的爭論也引發過恐慌。它是科學傳播裡最不體面、也最無法迴避的部分:你必須在資訊不完整的情況下,為幾億人做一個可能出錯的判斷,然後在資料變化時公開改口。

用兩年談成的合作,用兩週啟動的戰時聯盟

如果說這場對話有明亮的部分,這裡就是。

柯林斯在 NIH 做的一件事,是打破公共部門和私營部門之間的那道牆。他找了幾位藥企的首席科學家聊,發現雙方都活在刻板印象裡。學術界覺得藥企的科學家不夠聰明,只想賺錢;藥企覺得學術界的科學家只想發論文,不在乎救人。

他說,後來發現這兩種刻板印象都是錯的。

花兩年時間,促成了“加速藥物夥伴關係”(AMP)。第一批三個專案:阿爾茨海默病、糖尿病、類風溼關節炎與狼瘡。規則很簡單:必須開放獲取,否則 NIH 不參與;企業必須出錢,NIH 出一半,企業出一半。

結果超出預期。專案從三個變成六個,2022 年還要加心臟衰竭,變成七個。參與的人彼此熟悉了。

這段鋪墊在後面派上了用場。AMP 花了兩年啟動,ACTIV 只花了兩週。ACTIV 是加速新冠治療干預和疫苗的公私合作聯盟,約 100 人,一半來自產業界,一半來自政府和學術界,全部放下手上的事來做這一件事。

被問到怎麼做到兩週啟動 100 人,他的回答是:把律師留在門外。

成果是具體的。疫苗主方案的設計、每個試驗 3 萬人規模的樣本量計算,都是這個小組定的。至少 20 種治療藥物在 ACTIV 支援下以創紀錄速度完成試驗,包括那些被證明有效的單克隆抗體。

基因組、大腦,以及總統一句正確的問題

柯林斯在 2009 年接手 NIH,此後的 12 年正好是生物醫學加速最猛的一段。

他列舉了一串:基因編輯,現在可以治癒鐮狀細胞病,2009 年完全不可想象;單細胞生物學,可以逐個問細胞在做什麼並得到答案;癌症的精準治療和免疫療法,從冷門領域變成最熱的方向。

新冠疫苗是這條曲線的延續。理解 mRNA、理解冠狀病毒和刺突蛋白、把結構生物學和免疫學與基因組學打包在一起,最後在 11 個月內做出疫苗。他說 2009 年的自己絕不會想到這成為可能。

他把自己在 NIH 的角色形容為“助產士”。院長這個位置有一種獨特的召集權,能看到整個生物醫學研究的全景,識別出哪些領域已經準備好爆發,然後把人拉在一起。這些人彼此不認識,甚至聽不懂對方的學術語言。

BRAIN Initiative 是他的最愛之一。目前約 600 名研究者參與,其中超過一半是工程師,不是傳統意義上的生物學家。他提到《自然》雜誌上一期整刊都是這個專案的產出,給出了大腦細胞的普查圖譜。他的博士訓練是量子力學,所以他格外喜歡這種跨學科的組合。

他記得在白宮東廳宣佈這個專案的那天。奧巴馬完全理解,也真心熱愛科學。柯林斯提到幾次在橢圓形辦公室和總統單獨談科學的時刻,只有他們兩個人。他說那是一種饋贈。

關於奧巴馬對科學的理解,對話裡有一段很有意思的旁證。這位計算機背景的播客主聽過奧巴馬談人工智慧,講窄 AI 與強 AI 的區別,技術層面和哲學層面都過關,讓人懷疑是不是有人在耳邊提示。

柯林斯的解釋是:他聽了一大批專家的意見。在滿屋科學家的討論中,他會提出一個極其鋒利的問題。他不需要知道答案,他知道的是哪個問題該問。

這背後是真實的好奇心,沒有表演成分。像一個混進了這間辦公室的孩子,得到了和世界頂級專家聊天的機會。

一個做科學家的基督徒

柯林斯在二十多歲讀醫學院時成為信徒。起因很樸素:他意識到自己從沒認真想過生命的意義、為什麼我們在這裡、死後會怎樣、是否存在神。科學對這些問題的幫助有限,他必須去別處找答案。

他的推理路徑是這樣的:無神論是他原先的立場,但它斷言了一個全稱否定命題,而科學家不該做這種斷言;不可知論有吸引力,但有點像和稀泥;於是他繼續追問,為什麼信的人會信。

結論是,他找不到證明,但在他看來說服力相當強。他最終“連踢帶打”地成了基督徒。當時有人預言他的腦袋會炸,因為這兩套世界觀不相容。

他說,在他身上從來沒有不相容過。同一天裡處理一個問題,可以既有嚴格的科學部分,也有精神的部分。新冠疫苗是最典型的例子:它既是驚人的科學成就,也是祈禱的回應。

他提到薩姆·哈里斯(Sam Harris)在他被提名為 NIH 院長時寫的那篇著名專欄,大意是讓一個信神的人掌管 NIH 是個可怕的錯誤,他會毀掉這個機構。

柯林斯沒有反駁,他只是說,自己有證詞。

希欽斯、威士忌和鐵磨鐵

克里斯托弗·希欽斯(Christopher Hitchens)是堅定的無神論者,也是柯林斯的朋友。希欽斯稱他是“在世最偉大的美國人之一”,也說過他是自己見過的最虔誠的信徒之一。希欽斯還說過,柯林斯在為最終奪走他生命的那種癌症做基因組測序。

兩人的關係起步很糟。在一場知識分子晚宴上,希欽斯對柯林斯提的一個問題表現得極其刻薄。柯林斯的反應是:行,那我們想想怎麼進行一場更文明的對話。

之後他逐漸欣賞希欽斯的智力,也享受和他的交鋒。“鐵磨鐵。”想搞清楚自己到底站在哪裡,沒有比遇到一個完全在另一個座標系裡、而且有天賦挑戰一切的人更好的方式。通常配上一兩杯蘇格蘭威士忌。

對話不總是關於信仰。有時是科學,希欽斯對科學著迷;有時是托馬斯·傑斐遜。柯林斯說,他知道那一定會有意思。

希欽斯確診癌症後,柯林斯成了他的盟友,幫他在各種治療方案之間找路徑,也許讓他多在這顆星球上待了六個月。柯林斯記得在他市中心公寓裡,端著一杯酒,聊各種事的那些下午。

七十一歲,不怕死,但不想浪費時間

被問到死亡時,柯林斯的回答很乾脆:不怕,但也不期待;不想趕時間,因為還有些事能做。

他 71 歲。他說自己知道時間不是無限的,想把它用在有意義的地方。他還沒準備好當全職高爾夫球手,但也不確定那件有意義的事到底是什麼。

他提到 16 年前寫的《上帝的語言》(The Language of God),試圖說明科學與信仰在他眼裡如何相容。他驚訝於有很多人對這本書感興趣,因為他們厭倦了兩個極端的噪音:一端是道金斯,另一端是神創論者。人們覺得總該有一條能共存的路。

他後來創辦了 BioLogos 基金會,為了當 NIH 院長不得不退出,結果這個機構反而蓬勃發展,現在有數百萬人訪問。他覺得也許這個領域還有事可做,也許那本書該出第二版了。

關於“遺產”這個詞,他明顯不太自在。他說這個提法有點自我推銷的味道。10 月 5 日他宣佈卸任那天,收到了大量回應,有些來自熟人,有些來自完全不認識的人,講某件他參與過的事如何改變了他們的生活。他說,那就夠了。

他不想建一座紀念碑,也不需要一尊雕像。

生命的意義:一段讀不下去的登山寶訓

被逼到牆角,要求用三句話回答生命的意義,柯林斯先宣告這不是科學能回答的問題,然後給出了他的答案。

我們在這裡只停留一瞬,而存在本身在某種他不能完全理解的方式下會延續下去。在這一瞬裡,我們被要求讓世界變得好一點,去愛別人,讓利他的本能多發揮一點,讓自私的本能少一點。用他的話說,就是活出登山寶訓。

他說,讀過那段之後就再也無法當作沒讀過。那些八福,那些祝福,那就是我們該做的事。生命的意義就是朝那個標準努力,同時清楚地知道你會一次又一次失敗,而神會寬恕你。

最後落在一句話上:希望能在世界上多放一點點愛進去。

六千萬人的猶豫,和一場關於真相的流行病

回到地面。柯林斯說,他完全可以理解疫苗猶豫。人們被來自各個方向互相沖突的資訊轟炸:政治人物給一些,網際網路給很多,部分媒體樂於製造恐懼以獲取自己的利益。

他說自己能做的是更好地傾聽。因為他發現一個常見錯誤:我們總以為自己知道別人猶豫的原因,而實際情況往往不是這樣。真實原因五花八門,有人擔心研發太快、流程被砍,有人擔心長期副作用。

至於後者,他可以給出一個合理回應:其他疫苗沒有出現過這類長期問題,也沒有理由認為這一款會不同。但他不能絕對地說“不可能”。

他對困惑和恐懼的人抱有同情。對明知資訊為假卻繼續傳播的人,他沒有同情。他說這些人在奪走生命。

然後他把話題擴大了一層。他說這個國家還有另一場流行病,那就是真相作為決策依據的地位正在喪失。該不該給自己或孩子打疫苗,本該由客觀事實來回答,現在卻由一個語氣強烈的人的觀點、或者兩小時前刷到的帖子來回答。假資訊的數量只是表象,更深的一層在於,人們不再相信那種以權威口吻宣稱掌握真理的說話方式。

他甚至提到了 2020 年大選是否公正這類問題。分裂本身已經夠糟,更糟的是失去了透過“到底什麼是真的”來化解分裂的能力。他說自己通常是樂觀主義者,但這件事讓他深切擔憂。

對話的另一方給了一個不那麼悲觀的視角:20 世紀的科學習慣以權威口吻講話,21 世紀必須換一種聲音。人們牴觸的也許正是那種腔調。在觀念的競爭裡,謙卑和善意會贏。

柯林斯的回應是:我同意,而且這很符合聖經。

Joe Rogan、伊維菌素和那 700 個孩子

這部分被明確要求必須談。

柯林斯先做了區分。他不認為 Joe Rogan 吃伊維菌素這件事本身有多嚴重。真正的問題在於,Rogan 在人們正在死去的時刻,相當公開地對疫苗表達負面態度。

美國有 70 萬人死於新冠,其中至少 10 萬是未接種者的“不必要的死亡”。在這種情況下繼續助推這種態度,是不負責任的。

關於伊維菌素,他說這藥之所以引發關注,部分原因是它激發了很多人的想象力,以至於有人服用了給牲畜用的劑量,因為過量而病得不輕。他提到一項彙總了所有相關研究的綜述,結論是它很可能無效。ACTIV-6 試驗已經隨機入組約 400 名患者,可能一個月內就有嚴格對照的答案。

對話在這裡做了反駁:Rogan 並沒有說“別聽科學的”,他說的是“可以提問”,可以問疫苗對特定人群的風險收益比。他還經常舉出接種後出現嚴重不良反應的個例。

柯林斯的回答分兩層。第一層:科學不靠個例證據推進。第二層,他講了健康人群為什麼也該打疫苗。他提到一位身高接近兩米、肌肉極其發達的職業摔角手,感染後幾乎死掉,康復後主動站出來做疫苗宣傳。因為這個病毒不在乎你多健康、練得多好。

他給了一組資料:目前美國 ICU 裡的新冠患者平均年齡不到 50 歲;死於新冠的兒童有 700 名,其中一些有肥胖等基礎病,但很多沒有。

年輕人重症率低,孩子更低,這是事實。但不是零。如果疫苗足夠安全有效,那麼所有人都該用上它。每個人都在降低自己的風險,只是降的幅度不同。

德爾塔之後,還會有下一個嗎

柯林斯對變異株的擔憂是明確的。德爾塔在幾個月內席捲全球,靠的是極強的傳播力。

他說了一句很有意思的話:病毒如果不是那麼可怕,本來是很美的。任何想理解進化如何在實時中發生的人,都該去研究 SARS-CoV-2。阿爾法、貝塔、伽馬、德爾塔,靠適應度上很微小的差異輪番掃過人群。

核心問題在於:德爾塔是不是終點站?它是不是已經足夠適應,以至於別的毒株無法取代它?他說不知道。英國已經出現德爾塔的亞系 AY.4,似乎傳播力更強一些,這可能是新變化的第一絲跡象。

真正的擔心是:會不會出現一種差異大到疫苗失效的毒株。

這裡有一段對免疫系統的讚美。疫苗讓你對最初的武漢毒株產生免疫,而你的免疫系統足夠聰明,會生成多樣化的抗體,覆蓋病毒後來發生的一些小變化。即便是差異最大的貝塔株,防護效果看起來仍然不錯。但如果某個毒株跑得足夠遠,這個優勢未必一直成立。

好訊息是,mRNA 技術讓重新設計疫苗變得很快,幾千人的臨床試驗確認抗體水平之後就能推進。但他不想走到那一步,因為中間會有人失去生命。

最好的辦法是減少感染人數。病毒只有在人身上覆制,才可能產生變異。

具體處方:讓美國那 6400 萬還沒接種的成年人去打疫苗,讓孩子去打,讓該打加強針的人去打,在疫情真正結束之前堅持室內戴口罩和保持距離。同時,中低收入國家大部分人還沒開始接種,那很可能是下一個變異株出現的地方,而且它會像過去 22 個月反覆發生的那樣,迅速穿過整個世界。

一件顯而易見卻沒做好的事

訪談裡有一個雙方高度一致的判斷:快速居家檢測本該從第一天起就是解決方案的核心。

理由很直接。沒人反對檢測,這是它最大的優勢。而且這恰好是美國擅長的事:工程師和製造商能迅速把產能拉起來。更重要的是,檢測給的是資訊和自由,讓人自己決定接下來做什麼。

柯林斯完全同意,並且給出了 NIH 的實際動作。國會撥了 10 億美元,建立了“快速診斷加速計劃”(RADx)。NIH 把自己變成一個風險投資機構,邀請所有有小企業或學術實驗室提出居家檢測方案的人來提案,然後把他們扔進一個由商業專家、工程師、技術專家、懂供應鏈和製造的人組成的“鯊魚 tank”。

成果是:目前每天約有 200 萬次檢測基於這個專案的產出,包括你現在能在藥房貨架上買到的多數居家檢測。12 月預計有 4.1 億份檢測可用。如果再有一兩個平臺獲批,月產能可以到 5 億份。NIH 現在還在幫 FDA 做驗證實驗室。

他也承認了失誤。疫情最初幾個月,檢測全部集中在大實驗室,樣本要郵寄,結果有時五天後才回來,而那時你已經傳染了十幾個人。這個模型從一開始就錯了。而當時很多人的理由是:抗原側流檢測會有假陽性和假陰性,所以要堅持 PCR。他的回應是:沒有一種檢測是完美的,但一種沒人願意用、也拿不到的檢測,是最糟的設定。

照鏡子:黑猩猩、狗和萊什曼病

訪談最後提到一個具體的指控:NIH 被指資助了一篇論文,裡面有把鎮靜的幼犬頭部塞進裝有攜帶疾病的白蛉的小容器的影象。

柯林斯說這個故事不是真的,至少論文裡標註 NIH 為資助來源這一點不準確。

但由此引出的問題更大:一個每年資助海量研究的機構,如何保證這些研究的倫理底線?

他給了一個正面的例子。2015 年 NIH 宣佈不再支援任何涉及黑猩猩的生物醫學研究。這個決定源於一次深度審視:我們在這個階段真的還能從侵入性黑猩猩實驗裡得到必不可少的東西嗎?國家科學院組織專家組做了評估,結論是不需要。這些黑猩猩很多是當年因為被認為適合研究 HIV 而買來的,結果並不適合,之後被留在靈長類實驗室裡,人們不斷給它們找新課題,但科學上並不成立。

他說這個決定招來不少科學界批評,說他向動物權利團體投降。但在他看來是對的。

他也為另一類研究做了辯護。有些疾病只有犬類能作為宿主,比如萊什曼病,比如淋巴絲蟲病。佐治亞州有一項 NIH 支援的研究讓狗感染寄生蟲,因為那是判斷治療是否有效的唯一模型。他說,如果一項經過嚴格審查的動物研究能救一個孩子,那麼即使讓他不舒服,那仍然是正確的選擇。

他的判斷是:宣稱所有動物研究都該取消,本身也是一種不倫理,因為那等於讓一批本來有希望的人失去希望。

他還補了一句,從個人角度看,工廠化養殖和其他場景下對動物的處置,倫理問題比醫學研究嚴重得多。

為什麼在最好玩的時候下臺

柯林斯的卸任理由講得很實在。歷史上沒有哪位 NIH 院長在一位總統任命後跨越超過一位總統。他被奧巴馬任命,被特朗普留任,又被拜登留任,這本身已經罕見。

他說科研機構需要新的視野,12 年對同一位領導者來說太長了。而且如果他不打算幹完拜登整個四年任期,就不該拖到太晚才釋放訊號,因為總統要找人、要提名、要過參議院確認,而這個流程現在完全不可預測。這件事必須現在做。

他 5 月底就決定了。情緒是複雜的,因為他喜歡 NIH,也喜歡這份工作。過去 20 個月他每週工作 100 小時。他不介意未來能有一點時間,認真想想下一章該寫什麼,因為他覺得自己還沒做完。

對話裡有人拿喬治·華盛頓和泰德·威廉姆斯作比。後者在最後一場比賽的最後一個打席打出本壘打,然後轉身離開。領導者在合適的時候走下臺階,很難,但很好看。

可以立刻用上的幾件事

  • 聽到“功能增益”這個詞時,先問一句:說的是廣義的、幾乎所有生物醫學研究都涉及的功能增益,還是特指的 EPPP,即增強已知人類病原體傳播力或致病性的實驗。這兩件事的監管強度差了幾個數量級,混為一談的討論基本沒有意義,包括很多政治人物的發言。
  • 判斷一個科學爭議時,區分兩件事:結論本身,和得出結論的程式。柯林斯對武漢病毒所實驗的辯護,核心是“它不符合當時各方共同認可的門檻”,而不是“這些實驗絕對安全”。前者可以核查,後者不能。
  • 看到“某人反覆橫跳”的指控時,去查時間線。口罩建議的變化有兩個具體原因:口罩短缺,以及早期不知道無症狀傳播。資料變了建議就變,這是科學正常工作方式,不是失信的證據。
  • 如果你身邊有人對疫苗猶豫,先別急著講道理。柯林斯說他花了一年多學的一件事,就是不要假設自己知道對方在擔心什麼。先問,聽完再回應,而且回應時不要讓對方覺得你在暗示他不如你聰明。
  • 關注快速居家檢測這條線。它是少數“沒人反對、成本低、給個人自由而非限制”的防疫手段。RADx 這類專案的進展值得追蹤,因為它決定了下一次疫情裡普通人手裡有沒有工具。
  • 對“科學界已經有嚴格監管”這種說法保持一層警覺。柯林斯自己就在推動重新審視現行門檻,理由是這個框架已經執行了幾年、該看經驗資料了。一個健康的科學機構應該能公開討論自己的規則是否需要改,而不是把現行規則當成不可質疑的結論。
  • 如果你關心科學與信仰的爭論,可以把注意力從“誰對誰錯”挪到柯林斯和希欽斯那種關係上。兩個人世界觀完全對立,還能一起喝威士忌、一起在治療方案裡找出路。這在今天的公共討論裡幾乎絕跡了,但它確實存在過,也確實可行。
文稿來自公開 Kaggle 資料集(rajneesh231/lex-fridman-podcast-transcript),為早期自動轉錄存檔,可能存在識別錯誤。
The following is a conversation with Francis Collins, director of the NIH, the National Institutes of Health, appointed and reappointed to the role by three presidents, Obama, Trump, and Biden. He oversees 27 separate institutes and centers, including NIAID, which makes him Anthony Fauci's boss. At the NIH, Francis helped launch and led a huge number of projects that pushed the frontiers of science, health, and medicine, including one of my favorites, the BRAIN Initiative, that seeks to map the human brain and understand how the function arises from the neural circuitry. Before the NIH, Francis led the Human Genome Project, one of the largest and most ambitious efforts in the history of science. Given all that, Francis is a humble, thoughtful, kind man, and because of this, to me, he's one of the best representatives of science in the world. He is a man of God, and yet, also a friend of the late Christopher Hitchens, who called him, quote, one of the greatest living Americans. This is a Lex Friedman podcast. To support it, please check out our sponsors in the description. And now, here's my conversation with Francis Collins. Science at its best is a source of hope. So for me, it's been difficult to watch, as it has during the pandemic, become at times a source of division. What I would love to do in this conversation with you is touch some difficult topics, and do so with empathy and humility so that we may begin to regain a sense of trust in science, and that it may once again become a source of hope. I hope that's okay with you. I love the goal. Let's start with some hard questions. You called for, quote, thorough, expert driven, and objective inquiry into the origins of COVID 19. So let me ask, is there a reasonable chance that COVID 19 leaked from a lab? I can't exclude that. I think it's fairly unlikely. I wish we had more ability to be able to ask questions of the Chinese government and learn more about what kind of records might have been in the lab that we've never been able to see. But most likely, this was a natural origin of a virus, probably starting in a bat, perhaps traveling through some other intermediate, yet to be identified host, and finding its way into humans. Is answering this question within the realm of science, do you think, will we ever know? I think we might know if we find that intermediate host. And there has not yet been a thorough enough investigation to say that that's not going to happen. And remember, it takes a while to do this. With SARS, it was 14 years before we figured out it was the civet cat that was the intermediate host. With MERS, it was a little quicker to discover it was the camel. With SARS COVID 2, there's been some looking, but especially now with everything really tense between the US and China, if there's looking going on, we're not getting told about it. Do you think it's a scientific question or a political question? It's a scientific question, but it has political implications. So the world is full of scientists that are working together, but in the political space, in the political science space, there's tensions. What is it like to do great science in a time of a pandemic when there's political tensions? It's very unfortunate. Pasteur said science knows no one country. He was right about that. My whole career in genetics, especially, has depended upon international collaboration between scientists as a way to make discoveries, get things done. Scientists, by their nature, like to be involved in international collaborations. The Human Genome Project, for heaven's sake, 2,400 scientists in six countries working together, not worrying who is going to get the credit, giving all the data away. I was the person who was supposed to keep all that coordinated. It was a wonderful experience, and that included China. That was sort of their first real entry into a big international, big science kind of project, and they did their part. It's very different now. Continuing the line of difficult questions, especially difficult ethical questions. In 2014, U.S. put a hold on gain of function research in response to a number of laboratory biosecurity incidents, including anthrax, smallpox, and influenza. In December 2017, NIH lifted this ban because, quote, gain of function research is important in helping us identify, understand, and develop strategies and effective countermeasures against rapidly evolving pathogens that pose a threat to public health. All difficult questions have arguments on both sides. Can you argue the pros and cons of gain of function research with viruses? I can, and first let me say this term, gain of function, is causing such confusion that I need to take a minute and just sort of talk about what the common scientific use of that term is and where it is very different when we're talking about the current oversight of potentially dangerous human pathogens. As you know, in science, we're doing gain of function experiments all the time. We support a lot of cancer immunotherapy at NIH. Right here in our clinical center, there are trials going on where people's immune cells are taken out of their body, treated with a genetic therapy that revs up their ability to discover the cancer that that patient currently has, maybe even at stage four, and then give them back as those little ninja warriors go after the cancer. It sometimes works dramatically. That's gain of function. You gave that patient a gain in their immune function that may have saved their life. We've got to be careful not to say, oh, gain of function is bad. Most of what we do in science that's good involves quite a bit of that. We are all living with gains of function every day. I have a gain of function because I'm wearing these eyeglasses. Otherwise, I would not be seeing you as clearly. I'm happy for that gain of function. That's where a lot of confusion has happened. The kind of gain of function which is now subject to very rigorous and very carefully defined oversight is when you are working with an established human pathogen that is known to be potentially causing a pandemic and you are enhancing or potentially enhancing its transmissibility or its virulence. We call that EPPP, enhanced potential pandemic pathogen. That requires this very stringent oversight worked out over three years by the National Science Advisory Board on Biosecurity that needs to be looked at by a panel that goes well beyond NIH to decide are the benefits worth the risks in that situation. Most of the time, it's not worth the risk. Only three times in the last three or four years have experiments been given permission to go forward. They were all on influenza. So I will argue that if you're worried about the next pandemic, the more you know about the coming enemy, the better chance you have to recognize when trouble is starting. And so if you can do it safely, studying influenza or coronaviruses like SARS, MERS, and SARS CoV2 would be a good thing to be able to know about. But you have to be able to do it safely because we all know lab accidents can happen. I mean, look at SARS where there have been lab accidents and people have gotten sick as a result. We don't want to take that chance unless there's a compelling scientific reason. That's why we have this very stringent oversight. The experiments being done at the Wuhan Institute of Virology as a subaward to our grant to EcoHealth in New York did not meet that standard of requiring that kind of stringent oversight. I want to be really clear about that because there's been so much thrown around about it. Was it gain of function? Well, in the standard use of that term that you would use in science in general, you might say it was. But in the use of that term that applies to this very specific example of a potential pandemic pathogen, absolutely not. So nothing went on there that should not have happened based upon the oversight. There was an instance where the grantee institution failed to notify us about the result of an experiment that they were supposed to tell us where they mixed and matched some viral genomes and got a somewhat larger viral load as a result. But it was not EPPP. It was not getting into that zone that would have required this higher level of scrutiny. It was all bat viruses. These were not human pathogens. So they didn't cross a threshold within that gray area that makes for an EPPP? They did not. And anybody who's willing to take the time to look at what EPPP means and what those experiments were would have to agree with what I just said. What is the biggest reason it didn't cross that threshold? Is it because it wasn't jumping to humans? Is it because it did not have a sufficient increase in virulence or transmissibility? What's your sense? EPPP only applies to agents that are known human pathogens of pandemic potential. These were all bat viruses derived in the wild, not shown to be infectious to humans. Just looking at what happened if you took four different bat viruses and you tried moving the spike protein gene from one into one of the others to see whether it would bind better to the ACE2 receptor. That doesn't get across that threshold. And let me also say, for those who are trying to connect the dots here, which is the most troubling part of this, and say, well, this is how SARS CoV2 got started. That is absolutely demonstrably false. These bat viruses that were being studied had only about 80% similarity in their genomes to SARS CoV2. They were like decades away in evolutionary terms. And it is really irresponsible for people to claim otherwise. Speaking of people who claim otherwise, Rand Paul, what do you make of the battle of words between Senator Rand Paul and Dr. Anthony Fauci over this particular point? I don't want to talk about specific members of Congress, but I will say it's really unfortunate that Tony Fauci, who is the epitome of a dedicated public servant, has now somehow been targeted for political reasons as somebody that certain figures are trying to discredit, perhaps to try to distract from their own failings. This never should have happened. Here's a person who's dedicated his whole life to trying to prevent illnesses from infectious diseases, including HIV in the 1980s and 90s, and now probably the most knowledgeable infectious disease physician in the world, and also a really good communicator, is out there telling the truth about where we are with SARS CoV2 to certain political figures who don't want to hear it, and who are therefore determined to discredit him. And that is disgraceful. So with politicians, they often play games with black and white. They try to sort of use the gray areas of science and then paint their own picture. But I have a question about the gray areas of science. So like you mentioned, gain of function is a term that has very specific scientific meaning, but it also has a more general term. And it's very possible to argue that the, not to argue, not the way politicians argue, but just as human beings and scientists, that there was a gain of function achieved at the Wuhan Institute of Virology, but it didn't cross a threshold. I mean, there's a, it's a, but it could have too. So here's the thing. When you do these kinds of experiments, unexpected results may be achieved. And that's the gray area of science. You're taking risks with such experiments. And I am very uncomfortable that we can't discuss the uncertainty in the gray area of this. Oh, I'm comfortable discussing the gray area. What I'm uncomfortable with is people deciding to define for themselves what that threshold is based on sort of some political argument. The threshold was very explicitly laid out. Everybody agreed to that in the basis of this three years of deliberation. So that's what it is. If that threshold needs to be reconsidered, let's reconsider it, but let's not try to take an experiment that's already been done and decide that the threshold isn't what it was, because that really is doing a disservice to the whole process. I wish there was a discussion, even in response to Rand Paul, I know we're not talking about specific senators, but just that particular case, I'm saying stuff here. I wish there was an opportunity to talk about, given the current threshold, this is not gain of function. But maybe we need to reconsider the threshold and have an action. That's an opportunity for discussion about the ethics of gain of function. You said that there was three studies that passed that threshold with influenza. That's a fascinating human question, scientific question about ethics, because like you said, there's pros and cons. You're taking risks here to prevent horribly destructive viruses in the future, but you also are risking creating such viruses in the future. With nuclear weapons and nuclear energy, nuclear energy promises a lot of positive effects, and yet you're taking risks here. With mutually shared destruction, nations possessing nuclear weapons, a lot of people argue that nuclear weapons is the reason we've prevented world wars, and yet they also have the risk of starting world wars. And this is what we have to be honest about with the benefits and risks of science, that you have to make that calculation. What are the pros and what are the cons? I'm totally with you, but I want to reassure you, Lex, that this is not an issue that's been ignored. That this issue about the kind of gain of function that might result in a serious human pathogen has been front and center in many deliberations for a decade or more, involved a lot of my time along the way, by the way, and has been discussed publicly on multiple occasions, including two major meetings of the National Academy of Sciences, getting input from everybody and ultimately arriving at our current framework. Now, we actually back in January of 2020, just before COVID 19 changed everything, had planned and even charged that same National Science Advisory Board on Biosecurity to reconvene and look at the current framework and say, do we have it right? Let's look at the experience over those three years and say, is the threshold too easy, too hard? Do we need to reconsider it? Let's look at the experience. COVID came along, the members of the board said, please, we're all infectious disease experts. We don't have time for this right now. But I think the time is right to do this. I'm totally supportive of that. And that should be just as public a discussion as you can imagine about what are the benefits and the risks. And if somebody decided, ultimately, this came together and said, we just shouldn't be doing these experiments under any circumstances. If that was the conclusion, well, that would be the conclusion. But it hasn't been so far. If we can briefly look out into the next hundred years on this. I apologize for the existential questions. But it seems obvious to me that as gain of function type of research and development becomes easier and cheaper, it will become greater and greater risk. So if it doesn't no longer need to be contained within laboratories of high security, it feels like this is one of the greatest threats facing human civilization. Do you worry that at some point in the future a leaked manmade virus may destroy most of human civilization? I do worry about the risks. And at the moment where we have the greatest control, the greatest oversight is when this is federally funded research. But as you're alluding, there's no reason to imagine that's the only place that this kind of activity would go on. If there was an evil source that wished to create a virus that was highly pathogenic in their garage, the technology does get easier. And there is no international oversight about this either that you could say has the same stringency as what we have in the United States. So yes, that is a concern. It would take a seriously deranged group or person to undertake this on purpose, given the likelihood that they too would go down. We don't imagine there are going to be bioweapons that only kill your enemies and don't kill you. Sorry, we're too much alike for that to work. So I don't see it as an imminent risk. There's lots of scary novels and movies written about it. But I do think it's something we have to consider. What are all the things that ought to be watched? You may not know that if somebody is ordering a particular oligonucleotide from one of the main suppliers, and it happens to match smallpox, they're going to get caught. So there is effort underway to try to track any nefarious actions that might be going on. In the United States or internationally? Is there an international collaboration of try to track this stuff? There is some. I wish it were stronger. This is a general issue, Lex, in terms of do we have a mechanism, particularly when it comes to ethical issues, to be able to decide what's allowable and what's not and enforce it. I mean, look where we are with germline genome editing for humans, for instance. There is no enforcement mechanism. There's just bully pulpits and governments that get to decide for themselves. You talked about evil. What about incompetence? Does that worry you? I was born in the Soviet Union. My dad, a physicist, worked at Chernobyl. That comes to mind. That wasn't evil. I don't know what word you want to put it. Maybe incompetence is too harsh. Maybe it's the inherent incompetence of bureaucracy. I don't know. But for whatever reason, there was an accident. Does that worry you? Of course it does. We know that SARS, for instance, did manage to leak out of a lab in China two or three times. At least in some instances, people died, fortunately quickly contained. All one can do in that circumstance, because you need to study the virus and understand Taking all that we've learned about the genome and applying it to cancer to make individual cancer treatment really precision. And developing cancer immunotherapy, which seemed like sort of a backwater into some of the hottest science around. All those things sort of erupting. And much more to come, I'm sure. We're on an exponential curve of medical research advances, and that's glorious to watch. And of course, COVID 19, as a beneficiary of decades of basic science, understanding what mRNA is, understanding basics about coronaviruses and spike proteins and how to combine structural biology and immunology and genomics into this package that allows you to make a vaccine in 11 months. Just I would never have imagined that possible in 2009. So to have been able to kind of be the midwife, helping all of those things get birthed, that's been just an amazing 12 years. And as NIH director, you have this convening power and this ability to look across the whole landscape of biomedical research and identify areas that are just like ready for something big to happen. But it isn't going to happen spontaneously without some encouragement, without pulling people together from different disciplines who don't know each other and maybe don't know how to quite understand each other's scientific language and create an environment for that to happen. That has been just an amazing experience. I mean, I mentioned the Brain Initiative as one of those. The Brain Initiative right now, I think there's about 600 investigators working on this. Last week, the whole issue of Nature magazine was about the output of the Brain Initiative basically now giving us a cell census of what those cells in the brain are doing, which has just never been imaginable. And interestingly, more than half of the investigators in the Brain Initiative are engineers. They're not biologists in a traditional sense. I love that. Maybe partly because my PhD is in quantum mechanics. So I think it's really a good idea to bring disciplines together and see what happens. That's an exciting thing. And I will not ever forget having the chance to announce that program in the East Room in that White House with President Obama, who totally got it and totally loved science and working with him in some of those rare moments of sort of one on one conversation in the Oval Office, just him and me about science. That's a gift. What's it like talking to Barack Obama about science? He seems to be a sponge. I've heard him. I'm an artificial intelligence person. And I've heard him talk about AI. And it was like, it made me think, is somebody like whispering in his ear or something? Because he was saying stuff that totally passed the BS test, like he really understands stuff. He does. That means he listened to a bunch of experts on AI. He was explaining the difference between narrow artificial intelligence and strong AI. He was saying all this, both technical and philosophical stuff. And it just made me, I don't know, it made me hopeful about the depth of understanding that a human being in political office can attain. That gave me hope as well, and having those experiences. Oftentimes in a group, I mean, another example was trying to figure out, how do we take what we've learned about the genome and really apply it at scale to figure out how to prevent illness, not just treat it, but prevent it, out of which came this program called All of Us, this million strong American cohort of participants who make their electronic health records and their genome sequences and everything else available for researchers to look at. That came out of a couple of conversations with Obama and others in his office, and he asked the best questions. That was what struck me so much. I mean, a room full of scientists, and we'd be talking about the possible approaches, and he would come up with this incredibly insightful penetrating question. Not that he knew what the answer was going to be, but he knew what the right question was. I think the core to that is curiosity. I don't think he's even like, he's trying to be a good leader. He's legit curious. Yes. Legit. That he, almost like a kid in a candy store, gets to talk to the world experts. He somehow sneaked into this office and gets to talk to the world experts. That's the kind of energy that I think leads to beautiful leadership in the space of science. Indeed. Another thing I've been able to do as director is to try to break down some of the boundaries that seem to be traditional between the public and the private sectors. When it comes to areas of science that really could and should be open access anyway, why don't we work together? That was obvious early on. After identifying a few possible collaborators who are chief scientists of pharmaceutical companies, it looked like we might be able to do something in that space. Out of that was born something called the Accelerating Medicines Partnership, AMP. It took a couple of years of convening people who usually didn't talk to each other. There was a lot of suspicion. Academic scientists saying, oh, those scientists in pharma, they're not that smart. They're just trying to make money. The academic scientists getting the rap from the pharmaceutical scientists, all they want to do is publish papers. They don't really care about helping anybody. We found out both of those stereotypes were wrong. Over the course of that couple of years, we built a momentum behind three starting projects, one on Alzheimer's, one on diabetes, one on rheumatoid arthritis and lupus. Very different, each one of them trying to identify what is an area that we both really need to see advance and we could do better together. It's going to have to be open access, otherwise NIH is not going to play. Guess what, industry? If you really want to do this, you got to have skin in the game. We'll cover half the cost. You got to cover the other half. I love it. Enforcing open access, resulting in open science. Millions of dollars gone into this and it has been a wild success. After many people were skeptical, a couple of years later, we had another project on Parkinson's. More recently, we added one on schizophrenia. Just this week, we added one on gene therapy, on bespoke gene therapy for ultra rare diseases, which otherwise aren't going to have enough commercial appeal. If we did this together, especially with FDA at the table, and they have been, we could make something happen, turn this into a standardized approach where everything didn't have to be a one off. I'm really excited about that. What began as three projects is six and it's about to be seven next year with a heart failure and all of us have gotten to know each other. If it weren't for that background when COVID came along, it would have been a lot harder to build the partnership called ACTIV, which has been my passion for the last 20 months, accelerating COVID 19 therapeutic interventions and vaccines. We just had our leadership team meeting this morning. It was amazing what's been accomplished. That's pretty much 100 people who dropped everything just to work on this, about half from industry and half from government and academia. That's how we got vaccine master protocols designed. We all agreed about what the endpoints had to be and you wondered why are there 30,000 participants in each of these trials? That's because of ACTIV's group mapping out what the power needed to be for this to be convincing. Same with therapeutics. We have run at least 20 therapeutic agents through trials that ACTIV supported in record time. That's how we got monoclonal antibodies that we know work. That would not have been possible if I didn't already have a sense of how to work with the private sector that came out of AMP. AMP took two years to get started. ACTIV took two weeks. We just kept the lawyers. Wow, to get 100 people over? Yeah, kept the lawyers out of the room and away we went. Now you're going to get yourself in trouble. I do hope one day the story of this incredible vaccine development of vaccine protocols and trials and all this kind of details, the messy beautiful details of science and engineering that led to the manufacturing, the deployment and the scientific test. It's such a nice dance between engineering in the space of manufacturing the vaccines. You start before the studies are complete, you start making the vaccines just in case that if the studies proved to be positive, then you can start deploying them just like so many parties, like you said, private and public playing together. That's just a beautiful dance that is one of the, for me, the sources of hope in this very tricky time where there's a lot of things to be cynical about in terms of the games politicians play and the hardship experience of the economy and all those kinds of things. That to me, this dance was a vaccine development was done just beautifully and it gives me hope. It does me as well. And it was in many ways the finest hour that science has had in a long time being called upon when every day counted and making sure that time was not wasted and things were done rigorously, but quickly. So, you're incredibly good as a leader of the NIH. It seems like you're having a heck of a lot of fun. Why step down from this role after so much fun? Well, no other NIH director has served more than one president after being appointed by one. You're sort of done. And the idea of being carried over for a second presidency with Trump and now a third one with Biden is unheard of. I just think, Lex, that scientific organizations benefit from new vision and 12 years is a really long time to have the same leader. And if I wasn't going to stick it out for the entire Biden four year term, it's good not to wait too late during that to signal an intent to step down because the president's got to find the right person, got to nominate them, got to get the Senate to confirm them, which is an unpredictable process right now. And you don't want to try to do that in the second half of somebody's term as president. This has got to happen now. So, I kind of decided back at the end of May that this should be my final year. And I'm okay with that. I do have some mixed emotions because I love the NIH. I love the job. It's exhausting. I'm traditionally for the last 20 months anyway, working 100 hours a week. It's just, that's what it takes to juggle all of this. And that keeps me from having a lot of time for anything else. And I wouldn't mind because I don't think I'm done yet. I wouldn't mind having some time to really think about what the next chapter should be. And I have none of that time right now. Do I have another calling? Is there something else I could contribute that's different than this? I'd like to find that out. I think the right answer is you're just stepping down to focus on your music career. That might not be a good plan for anything very sustainable. But I think that is a sign of a great leader as George Washington did stepping down at the right time. Ted Williams. Yes. He quit when I think he hit a home run on his last at bat and his average was 400 at the time. No one to walk away. I mean, it's hard, but it's beautiful to see in a leader. You also oversaw the human genome project. You mentioned the brain initiative, which has, it's a dream to map the human brain. And there's the dream to map the human code, which was the human genome project. And you have said that it is humbling for me and awe inspiring to realize that we have caught the first glimpse of our own instruction book, previously known only to God. How does that, if you can just kind of wax poetic for a second, how does it make you feel that we were able to map this instruction book, look into our own code, and be able to reverse engineer it? It's breathtaking. It's so fundamental. And yet, for all of human history, we're ignorant of the details of what that instruction book looked like. And then we crossed a bridge into the territory of the known. And we had that in front of us still written in a language that we had to learn how to read. And we're in the process of doing that and will be for decades to come. But we owned it, we had it. And it has such profound consequences. It's it's both a book about our history. It's a book of sort of the parts list of a human being, the genes that are in there and how they're regulated. And it's also a medical textbook that can teach us things that will provide answers to illnesses we don't understand, and alleviate suffering and premature death. So it's a pretty amazing thing to contemplate. And it has utterly transformed the way we do science. And it is in the process of transforming the way we do medicine, although much of that still lies ahead. You know, while we were working on the Genome Project, it was sort of hard to get this sense of a wellness, because it was just hard work. And you were getting, you know, another mega base, okay, this is good. But when did you actually step back and say, we did it? It's the profoundness of that. I mean, there were two points, I guess. One was the announcement on that June 26, 2000, where the whole world heard, well, we don't quite have it, but we got a pretty good draft. And suddenly, people are like realizing, oh, this is this a big deal. For me, it was more when we got the full analysis of it, published it in February 2001. And that issue of Nature paper that Eric Lander and Bob Waterston and I were the main authors, and we toiled over and tried to get as much insight as we could in there about what the meaning of all this was. But you also had this sense that we are such beginning readers here. We are still in kindergarten, trying to make sense out of this 3 billion letter book. And we're going to be at this for generations to come. You are a man of faith, Christian, and you are a man of science. What is the role of religion and of science in society and in the individual human mind and heart like yours? Well, I was not a person of faith when I was growing up. I became a believer in my 20s, influenced as a medical student by a recognition that I hadn't really thought through the issues of what's the meaning of life? Why are we all here? What happens when you die? Is there a God? Science is not so helpful in answering those questions. So I had to look around in other places and ultimately came to my own conclusion that atheism, which is where I had been, was the least supportable of the choices because it was the assertion of a universal negative, which scientists aren't supposed to do. And agnosticism came as an attractive option but felt a little bit like a cop out, so I had to keep going trying to figure out why do believers actually believe this stuff? And I came to realize it was all pretty compelling, that there's no proof. I can't prove to you or anybody else that God exists, but I can say it's pretty darn plausible. And ultimately, what kind of God is it that caused me to search through various religions and see, well, what do people think about that? And to my surprise, encountered the person of Jesus Christ as unique in every possible way and answering a lot of the questions I couldn't otherwise answer. And somewhat kicking and screaming, I became a Christian, even though at the time, as a medical student already interested in genetics, people predicted my head would then explode because these were incompatible worldviews. They really have not been for me. I am so fortunate, I think, that in a given day, wrestling with an issue, it can have both the rigorous scientific component and it can have the spiritual component. COVID 19 is a great example. These vaccines are both an amazing scientific achievement and an answer to prayer. When I'm wrestling with vaccine hesitancy and trying to figure out what answers to come up with, I get so frustrated sometimes and I'm comforted by reassurances that God is aware of that. I don't have to do this alone. So I know there are people like your friend, Sam Harris, who feel differently. Sam wrote a rather famous op ed in the New York Times when I was nominated as the NIH director saying, this is a terrible mistake. You can't have somebody who believes in God running the NIH. He's just going to completely ruin the place. Well, I have a testimonial. Christopher Hitchens, a devout atheist, if I could say so, was a friend of yours and referred to you as, quote, one of the greatest living Americans and stated that you were one of the most devout believers he has ever met. He further stated that you were sequencing the genome of the cancer that would ultimately claim his life and that your friendship, despite their differing opinions on religion, was an example of the greatest confirmed truth in modern times. What did you learn from Christopher Hitchens about life or perhaps what is a fond memory you have of this man with whom you've disagreed, but who is also your friend? Yeah, I loved Hitch. I'm sorry he's gone. Iron sharpens iron. There's nothing better for trying to figure out where you are with your own situation and your own opinions, your own worldviews, than encountering somebody who's completely in another space and who's got the gift, as Hitch did, of challenging everything and doing so over a glass of scotch or two or three. We got off to a rough start in an interaction we had at a rather highbrow dinner. He was really deeply insulting of a question I was asking. I was like, okay, that's fine. Let's figure out how we could have a more civil conversation. Then I really learned to greatly admire his intellect and to find the jousting with him. It wasn't all about faith, although it often was. It was really inspiring and innovating, energizing. Then when he got cancer, I became his ally, trying to help him find pathways through the various options and maybe helped him to stay around on this planet for an extra six months or so. I have the warmest feelings of being in his apartment downtown over a glass of wine talking about whatever. Sometimes it was science. He was fascinated by science. Sometimes it was Thomas Jefferson. Sometimes it was faith. I knew it would always be really interesting. He's now gone. Do you think about your own mortality? Are you afraid of death? I'm not afraid. I'm not looking forward to it. I don't want to rush it because I feel like I got some things I can still do here. As a person of faith, I don't think I'm afraid. I'm 71. I know I don't have an infinite amount of time left. I want to use the time I've got in some sort of way that matters. I'm not ready to become a full time golfer, but I don't quite know what that is. I do feel that I've had a chance to do amazingly powerful things as far as experiences, and maybe God has something else in mind. I wrote this book 16 years ago, The Language of God, about science and faith, trying to explain how, from my perspective, these are compatible. These are in harmony. They're complementary if you are careful about which kind of question you're asking. To my surprise, a lot of people seem to be interested in that. They were tired of hearing the extreme voices like Dawkins at one end and people like Ken Ham and Answers in Genesis on the other end saying, if you trust science, you're going to hell. They thought there must be a way that these things could get along, and that's what I tried to put forward. Then I started a foundation, BioLogos, which then I had to step away from to become NIH director, which has just flourished, maybe because I stepped away. I don't know. It now has millions of people who come to that website and they run amazing meetings. I think a lot of people have really come to a sense that this is okay. I can love science and I can love God, and that's not a bad thing. So maybe there's something more I can do in that space. Maybe that book is ready for a second edition. I think so. But when you look back, life is finite. What do you hope your legacy is? I don't know. This whole legacy thing is a little bit hard to embrace. It feels a little self promoting, doesn't it? I sort of feel like in many ways, I went to my own funeral on October 5th when I announced that I was stepping down and I got the most amazing responses from people, some of whom I knew really well, some of whom I didn't know at all, who were just telling me stories about something that I had contributed to that made a difference to them. That was incredibly heartwarming, and that's enough. I don't want to build an edifice. I don't have a plan for a monument or a statue. God help us. I do feel like I've been incredibly fortunate. I've had the chance to play a role in things that were pretty profound from the Genome Project to NIH to COVID vaccines, and I ought to be plenty satisfied that I've had enough experiences here to feel pretty good about the way in which my life panned out. We did a bunch of difficult questions in this conversation. Let me ask the most difficult one, that perhaps is the reason you turned to God. What is the meaning of life? Have you figured it out yet? Expect me to put that into three sentences. We only have a couple of minutes. At least hurry up. Well that's not a question that I think science helps me with, so you're going to push me into the faith zone, which is where I'd want to go with that. What is the meaning? Why are we here? What are we put here to do? I do believe we're here for just a blink of an eye and that our existence somehow goes on beyond that in a way that I don't entirely understand despite efforts to do so. I think we are called upon in this blink of an eye to try to make the world a better place, to try to love people, to try to do a better job of our more altruistic instincts and less of our selfish instincts, to try to be what God calls us to be, people who are holy, not people who are driven by self indulgence. And sometimes I'm better at that than others. But I think that for me as a Christian is a pretty clear, I mean, it's to live out the Sermon on the Mount. Once I read that, I couldn't unread it. All those beatitudes, all the blessings, that's what we're supposed to do. And the meaning of life is to strive for that standard, recognizing you're going to fail over and over again, and that God forgives you. Hopefully to put a little bit of love out there into the world. That's what it's about. Francis, I'm truly humbled and inspired by both your brilliance and your humility and that you would spend your extremely valuable time with me today. It was really an honor. Thank you so much for talking today. I was glad to. And you asked a really good question. So your reputation as the best podcaster has borne itself out here this afternoon. Thank you so much. Thanks for listening to this conversation with Francis Collins. To support this podcast, please check out our sponsors in the description. And now let me leave you with some words from Isaac Newton reflecting on his life and work. I seem to have been only like a boy playing on the seashore and diverting myself in now and then finding a smoother pebble or prettier shell than ordinary. Whilst the great ocean of truth lay all undiscovered before me. Thank you for listening and hope to see you next time. it in order to keep it from causing a broader pandemic, but you need to insist upon the kind of biosecurity, the BSL 2, 3, and 4 framework under which those experiments have to be done. Certainly at NIH, we're extremely rigorous about that, but you can't count on every human being to always do exactly what they're supposed to. There's a risk there, which is another reason why if we're contemplating supporting research on pathogens that might be the next pandemic, you have to factor that in, not just whether people are going to do something that we couldn't have predicted, where all of a sudden they created a virus that's much worse without knowing they were going to do that, but also just having an accident. That's in the mix when those estimates are done about whether the risk is worth it or not. Continuing on line of difficult questions. We're going to get to fun stuff after a while. We will soon, I promise. You are the director of the NIH. You are Dr. Anthony Fauci's, technically his boss. Yep. You have stood behind him. You have supported him, just like you did already in this conversation. It is painful for me to see division and distrust, but many people in politics and elsewhere have called for Anthony Fauci to be fired. When there are such calls of distrust in public about a leader like Anthony Fauci, who should garner trust, do you think he should be fired? Probably not. To do so would be basically to give the opportunity for those who want to make up stories about anybody to destroy them. There is nothing in the ways in which Tony Fauci has been targeted that is based upon truth. How could we then accept those cries for his firing as having legitimacy? It's a circular argument. They've decided they don't like Tony, so they make up stuff and they twist comments that he's made about things like gain of function, where he's referring to the very specific gain of function that's covered by this policy, and they're trying to say he lied to the Congress. That's simply not true. They don't like the fact that Tony changes the medical recommendations about what to do with COVID 19 over the space of more than a year. They call that flip flopping and you can't trust the guy because he says one thing last year and one thing this year. Well, the science has changed. Delta variant has changed everything. You don't want him to be saying the same thing he did a year ago. That would be wrong now. It was the best we could do then. People don't understand that or else they don't want to understand it. So when you basically whip up a largely political argument against a scientist and hammer at it over and over again to the point where he now has to have 24 seven security to protect him against people who really want to do violence to him. For that to be a reason to say that then he should be fired is to hand the evil forces the victory. I will not do that. Yet there's something difficult I'm going to try to express to you. So it may be your guitar playing. It may be something else, but there's a humility to you. It may be because you're a man of God. There's a humility to you that garners trust. And when you're in a leadership position representing science, especially in catastrophic events like the pandemic, it feels like as a leader, you have to go far above and beyond your usual duties. And I think there's no question that Anthony Fauci has delivered on his duties, but it feels like he needs to go above as a science communicator. And if there's a large number of people that are distrusting him, it's also his responsibility to garner their trust to gain their trust as a person who's the face of science. Do you, are you torn on this? The responsibility of Anthony Fauci of yourself to represent science, not just the communication of advising what should be done, but giving people hope, giving people trust in science and alleviating division. Do you think that's also responsibility of a leader or is that unfair to ask? I think the best way you give people trust is to tell them the truth. And so they recognize that when you're sharing information, it's the best you've got at that point. And Tony Fauci does that at every moment. I don't think him expressing more humility would change the fact that they're looking for a target of somebody to blame, to basically distract people from the failings of their own political party. Maybe I'm less targeted, not because of a difference in the way in which I convey the information. I'm less visible. If Tony were out of the scene and I was placed in that role, I'd probably be seeing a ratcheting up of that same targeting. I would like to believe that if Tony Fauci said that when I originally made recommendations not to wear masks, that was given on the, on the, our best available data. And now we know that is a mistake. So admit with humility that there's an error. That's not, that's not actually correct, but that's a, that's a statement of humility. And I would like to believe, despite the attacks, he would win a lot of people over with that. So a lot of people, as you're saying, would use that, see that here we go, here's that Dr. Anthony Fauci making mistakes. How can we trust them on anything? I believe if he was that public display of humility to say that I made an error, that would win a lot of people over. That's my, that's kind of my sense to face the fire of the attacks from politics. You have to, like politicians will attack no matter what, but the question is the people, to win over the people. The biggest concern I've had is that there was this, this stress of science that's been brewing and I'm, maybe you can correct me, but I'm a little bit unwilling to fully blame the politicians because politicians play their games no matter what. It just feels like this was an opportunity to inspire people with the power of science. The development of the vaccines, no matter what you think of those vaccines is one of the greatest accomplishments in the history of science. And the fact that that's not inspiring, listen, I host a podcast. Whenever I say positive stuff about the vaccine, I get to hear a lot of different opinions. The fact that I do is a big problem to me because it's an incredible, an incredible accomplishment of science. And so I, I, I, I, I'm sorry, but I have to put responsibility on the leaders, even if it's not their mistakes. That's what the leadership is. That's what leadership is. You take responsibility for the situation. I wonder if there's something that could have been done better to give people hope that science will save us as opposed to science will divide us. I think you have more confidence in the ability to get beyond our current divisions than I do after seeing just how deep and dark they have become. Tony Fauci has said multiple times the recommendation about not wearing masks was for two reasons, a shortage of masks, which were needed in hospitals and a lack of realization early in the course of the epidemic that this was a virus that could heavily infect asymptomatic people. As that changed, he changed. Now, did he make an error? No, he was making a judgment based on the data available at the time, but he certainly made that clear over and over again. It has not stopped those who would like to demonize him from saying, well, he just flip flopped. You can't trust a guy. He says one thing today and one thing tomorrow. Well, masks is a tricky one. So I'm actually early on, I'm a coauthor on a paper, one of many, but this was a survey paper overlooking the, the evidence. It's a summary of the evidence we have for the effectiveness of masks. It seems that it's difficult to do rigorous scientific study on masks. It is difficult. There's a lot of philosophical and ethical questions I want to ask you, but within this, it's back to your words and Anthony Fauci's words. When you're dealing with so much uncertainty and so much potential uncertainty about how catastrophic this virus is in the early days, and knowing that each word you say may create panic, how do you communicate science with the world? It's a philosophical, it's an ethical, it's a practical question. There was a discussion about masks a century ago and that too led to panic. So, I mean, I'm trying to put myself in the mind, in your mind, in the mind of Anthony Fauci in those early days, knowing that there's limited supply of masks. Like, what do you say? Do you fully convey the uncertainty of the situation of the, of the challenges of the supply chain? Or do you say that masks don't work? That's a complicated calculation. How do you make that calculation? It is a complicated calculation. As a scientist, your temptation would be to give a full brain dump of all the details of the information about what's known and what isn't known and what experiments need to be done. Most of the time that's not going to play well in a soundbite on the evening news. So you have to kind of distill it down to a recommendation that is the best you can do at that time with the information you've got. So you're a man of God. And we'll return to that to talk about some, some also unanswerable philosophical questions. But first let's linger on the vaccine because in the, in the religious, in the Christian community, there was some hesitancy with the vaccine. Still is. There's a lot of data showing high efficacy and safety of vaccines, of COVID vaccines, but still they are far from perfect as all vaccines are. Can you empathize with people who are hesitant to take the COVID vaccine or to have their children take the COVID vaccine? I can totally empathize, especially when people are barraged by conflicting information coming at them from all kinds of directions. I've spent a lot of my time in the last year trying to figure out how to do a better job of listening because I think we have all got the risk of assuming we know the basis for somebody's hesitancy. And that often doesn't turn out to be what you thought. And the variety of reasons is quite broad. I think a big concern is just this sense of uncertainty about whether this was done too fast and that corners were cut and there are good answers to that. Along with that, a sense that maybe this vaccine will have longterm effects that we won't know about for years to come. And one can say that hasn't been seen with other vaccines and there's no particular reason to think this one's going to be different than the dozens of others that we have experience with. But you can't absolutely say, no, there's no chance of that. So it does come down to listening and then trying in a fashion that doesn't convey a message that you're smarter than the person you're talking to because that isn't going to help to really address what the substance is of the concerns. But my heart goes out to so many people who are fearful about this because of all the information that has been dumped on them. Some of it by politicians, a lot of it by the internet, some of it by parts of the media that seem to take pleasure in stirring up this kind of fear for their own reasons. And that is shameful. I'm really sympathetic with the people who are confused and fearful. I am not sympathetic with people who are distributing information that's demonstrably false and continue to do so. They're taking lives. I didn't realize how strong that sector of disinformation would be. And it's been in many ways more effective than the means of spreading the truth. This is going to take us into another place. But Lex, if there's something I'm really worried about in this country, and it's not just this country, but it's the one I live in, is that we have another epidemic besides COVID 19. And it's an epidemic of the loss of the anchor of truth. That truth as a means of making decisions, truth as a means of figuring out how to wrestle with a question like, should I get this vaccine for myself or my children, seems to have lost its primacy. And instead, it's an opinion of somebody who expressed it very strongly, or some Facebook post that I read two hours ago. And for those to become substitutes for objective truth, not just, of course, for vaccines, but for many other issues, like was the 2020 election actually fair? This worries me deeply. It's bad enough to have polarization and divisions, but to have no way of resolving those by actually saying, okay, what's true here, makes me very worried about the path we're on. And I'm usually an optimist. Well, to give you an optimistic angle on this, I actually think that the sense that there's no one place for truth is just a thing that will inspire leaders and science communicators to speak, not from a place of authority, but from a place of humility. I think it's just challenging people to communicate in a new way, to be listeners first. I think the problem isn't that there's a lot of misinformation. I think that the internet and the world are distrustful of people who speak as if they possess the truth with an authoritarian kind of tone, which was, I think, defining for what science was in the 20th century. I just think it has to sound different in the 21st. In the battle of ideas, I think humility and love wins. And that's how science wins, not through having quote unquote truth. Because now everybody can just say, I have the truth. I think you have to speak, like I said, from humility, not authority. And so it's just challenges our leaders to go back and learn to be, pardon my French, less assholes and more kind. And like you said, to listen, to listen to the experiences of people that are good people, not the ones who are trying to manipulate the system or play a game and so on, but real people who are just afraid of uncertainty of hurting those they loved and so on. So I think it's just an opportunity for leaders to go back and take a class on effective communication. I'm with you on shifting more from where we are to humility and love. That's got to be the right answer. That's very biblical, by the way. We'll get there. I have to bring up Joe Rogan. I don't know if you know who he is. I do. He's a podcaster, comedian, fighting commentator, and my now friend. And Iver Mecton believer too. Yes. That is the question I have to ask you about. He has gotten some flack in the mainstream media for not getting vaccinated. And when he got COVID recently, taking Iver Mecton as part of a cocktail of treatments. The NIH actually has a nice page on Iver Mecton saying quote, there's insufficient evidence to recommend either for or against the use of Iver Mecton for the treatment of COVID 19 results from adequately powered, well designed and well conducted clinical trials are needed to provide more specific evidence based guidance on the role of Iver Mecton in the treatment of COVID 19. So let me ask, why do you think there has been so much attack on Joe Rogan and anyone else that's talking about Iver Mecton when there's insufficient evidence for or against? Well let's unpack that. First of all, I think the concerns about Joe are not limited to his taking Iver Mecton. Much more seriously, his being fairly publicly negative about vaccines at a time where people are dying. 700,000 people have died from COVID 19 estimates by Kaiser or at least 100,000 of those were unnecessary deaths of unvaccinated people. And for Joe to promote that further, even as this pandemic rages through our population is simply irresponsible. So yeah, the Iver Mecton is just one other twist. Obviously Iver Mecton has been controversial for months and months. The reason that it got particular attention is because of the way in which it seemed to have captured the imagination of a lot of people and to the point where they were taking doses that were intended for livestock and some of them got pretty sick as a result from overdosing on this stuff. That was not good judgment. The drug itself remains uncertain. There's a recent review that looks at all of the studies of Iver Mecton and basically concludes that it probably doesn't work. We are running a study right now. I looked at that data this morning in a trial called active six, which is one of the ones that my public private partnership is running. We're up to about 400 patients who've been randomized to Iver Mecton or placebo and should know perhaps as soon as a month from now in a very carefully controlled trial, did it help or did it not? So there will be an answer coming back to Joe again. I don't think the fact that he took the Iver Mecton and hoping it might work, uh, is that big a knock against him. It's more the conveying of we don't trust what science says, which is vaccines are going to save your life. We're going to trust what's on the internet that says Iver Mecton and hydroxychloroquine really do work, even though the scientific community says probably not. So let me push back in that a little bit. So he doesn't, he doesn't say, let's not listen to science. He doesn't say the vaccine don't get vaccinated. He says it's okay to ask questions. I'm okay with that. How risky is the vaccine for certain populations? What are the benefits and risks? There's other friends of Joe and friends of mine, like Sam Harris, who says, if you look at the data, it's obvious that the benefits outweigh the risks. And what Joe says is yes, but let's still openly talk about risks. And he often brings up anecdotal evidence of people who've had, uh, highly negative effects from vaccines. Science is not done with anecdotal evidence. And so you could infer a lot of stuff from the way he expresses it, but he also communicates a lot of interesting questions. Uh, and that's something maybe you can comment on this. You know, there's certain groups that are healthy. They have, they're younger, they have, they exercise a lot. They get the all, you know, nutrition and all those kinds of things. He shows skepticism on whether it's so obvious that they should get vaccinated. And the same is he makes this, he kind of presents the same kind of skepticism for kids, for young kids. So with empathy and, uh, you know, listening my Russian ineliquent description of what Joe believes, what, what is your kind of response to that? Why should certain categories of healthy and young people still get vaccinated? Do you think? Well, first just to say it's great for Joe to be a skeptic, to ask questions. We should all be doing that. But then the next step is to go and see what the data says and see if they're actually answers to those questions. So coming to healthy people, I've done a bunch of podcasts besides this one. The one I think I remember most was a podcast with a worldwide wrestling superstar. Very nice. He's about six foot six and just absolutely solid muscle. And he got COVID and he almost died. And recovering from that, he said, I've got to let my supporters know because you can imagine worldwide wrestling fans are probably not big embracers of the need for vaccines. And he want, he just turned himself into a spokesperson for the fact that this virus doesn't care how healthy you are, how much you exercise, what a great specimen you are. It wiped him out. And we see that, you know, the average person in the ICU right now with COVID 19 is under age 50. I think there's a lot of people still thinking, Oh, it's just those old people in the nursing homes. That's not going to be about me. They're wrong. And there are plenty of instances of people who were totally healthy with no underlying diseases, taking good care of themselves, not obese exercising who have died from this disease. 700 children have died from this disease. Yes. Some of them had underlying factors like obesity, but a lot of them did not. So it's fair to say younger people are less susceptible to serious illness, kids even less so, and then young adults, but it ain't zero. And if the vaccine is really safe and really effective, then you probably want everybody to take advantage of that. Even though some are dropping their risks more than others, everybody's dropping their risks. Some, are you worried about variants? So looking out into the future, what's your vision for all the possible trajectories that this virus takes in human society? I'm totally worried about the variants. Delta was such an impressive arrival on the scene in all the wrong ways. I mean, it took over the world in the space of just a couple months because of its extremely contagious ability. Viruses would be beautiful if they weren't terrifying. Yeah, exactly. I mean, this whole story of viral evolution scientifically is just amazingly elegant. Anybody who really wanted to understand how evolution works in real time, study SARS CoV 2, because it's not just Delta, it's Alpha, it's Beta, and it's Gamma, and it's the fact that these sweep through the world's population by fairly minor differences in fitness. So the real question many people are wrestling is, is Delta it? Is it such a fit virus that nothing else will be able to displace it? I don't know. I mean, there's now Delta AY4, which is a variant of Delta that at least in the UK seems to be taking over the Delta population as though it's maybe even a little more contagious. That might be the first hint that we're seeing something new here. It's not a completely different virus. It's still Delta, but it's Delta Plus. You know, the big worry is what's out there that is so different that the vaccine protection doesn't work. And we don't know how different it needs to be for the vaccine to start working. That's the terrifying thing about each of these variants. It's like, it's always a pleasant surprise that a vaccine seems to still have efficacy. And hooray for our immune system, may I say, because the vaccine immunized you against that original Wuhan virus. Now we can see that especially after two doses and even more so after a booster, your immune system is so clever that it's also making a diversity of antibodies to cover some other things that might happen to that virus to make it a little different. And you're still getting really good coverage. Even for beta, which was South Africa B1351, which is the most different, it looks pretty good. But that doesn't mean it will always be as good as that if something gets really far away from the original virus. Now the good news is we would know what to do in that situation. The mRNA vaccines allow you to redesign the vaccine like that and to quickly get it through a few thousand participants in a clinical trial to be sure it's raising antibodies and then bang, you could go. But I don't want to have to do that. There will be people's lives at risk in the meantime. And what's the best way to keep that from happening? Well, try to cut down the number of infections because you don't get variants unless the virus is replicating in a person. So how do we solve this thing? How do we get out of this pandemic? What's like, if you had a, like a wand or something, or you could really implement policies, what's the full cocktail of solutions here? It's a full cocktail. It's not just one thing. In our own country here in the US, it would be getting those 64 million reluctant people to actually go ahead and get vaccinated. There's 64 million people who didn't get vaccinated? Adults. Yes. Not even counting the kids. 64 million. Isn't that astounding? Get the kids vaccinated. Hopefully their parents will see that as a good thing too. Get those of us who are due for boosters boosted because that's going to reduce our likelihood of having breakthrough infections and keep spreading it. Convince people that until we're really done with this, and we're not now, that social distancing and mask wearing indoors are still critical to cut down the number of new infections. But of course, that's our country. This is a worldwide pandemic. I worry greatly about the fact that low and middle income countries have for the most part, not even gotten started with access to vaccines. And we have to figure out a way to speed that up because otherwise that's where the next variant will probably arrive. And who knows how bad it will be. And it will cross the world quickly as we've seen happen repeatedly in the last 22 months. I think I'm really surprised, annoyed, frustrated that rapid at home testing from the very beginning wasn't a big, big part of the solution. First of all, nobody's against it. That's one huge plus for testing. Everybody supports. Second of all, that's what America is good at is mask manufacturer stuff, like stepping up, engineers stepping up and really deploying it. Plus, without the collection of data is giving people freedom, is giving them information and then freedom to decide what to do with that information. It's such a powerful solution. I don't understand. Well, now I think the Biden administration is, I think, emphasized like the scaling of testing manufacturers. But I just feel like it's an obvious solution. Get a test that costs less than a dollar to manufacture, costs less than a dollar to buy. And just everybody gets tested every single day. Don't share that data with anyone. You just make the decisions. And I believe in the intelligence of people to make the right decision to stay at home when the test is positive. I am so completely with you on that. And NIH has been smack in the middle of trying to make that dream come true. We're running a trial right now in Georgia, Indiana, Hawaii. And where is the other one? Oh, Kentucky. Basically blanketing a community with free testing. That's beautiful. And look to see what happens as far as stemming the spread of the epidemic and measuring it by wastewater because you can really tell whether you've cut back the amount of infection in the community. Yeah, I'm so with you. We got off to such a bad start with testing. And of course, all the testing was being done for the first several months in big box laboratories where you had to send the sample off and put it through the mail somehow and get the result back sometimes five days later after you've already infected a dozen people. It was just a completely wrong model. But it's what we had. And everybody was like, oh, we got to stick with PCR because if you start using those home tests that are based on antigens, lateral flow, probably there's going to be false positives and false negatives. Okay, sure. No test is perfect. But having a test that's not acceptable or accessible is the worst setting. So we, NIH, with some requests from Congress, got a billion dollars to create this program called Rapid Acceleration of Diagnostics, RADx. And we turned into a venture capital organization, and we invited every small business or academic lab that had a cool idea about how to do home testing to bring it forward. And we threw them into what we called our shark tank of business experts, engineers, technology people, people who understood how to deal with supply chains and manufacturing. And right now today, there are about two million tests being done based on what came out of that program, including most of the home tests that you can now buy on the pharmacy shelves. We did that. And I wish we had done it faster, but it was an amazingly speedy effort. And you're right, companies are really good. Once they've got an FDA emergency use authorization, and we helped a lot of them get that, they can scale up their manufacturing. I think in December, we should have about 410 million tests for that month ready to go. And if we can get one or two more platforms approved, and by the way, we are now helping FDA by being their validation lab. If we can get a couple more of these approved, we could be in the half a billion tests a month, which is really getting where we need to be. Wow. Yeah, that's a dream. That's a dream for me. It seems like an obvious solution, engineering solution. Everybody's behind it, at least to hope versus division. I love it. Yeah. A happy story. A happy story. I was waiting for one. Yeah. All right. Well, one last dive into the not happy, but you won't even have to comment on it. Well, comment on the broader philosophical question. So NIH, again, I said, Joe Rogan is the first one who pointed me to this. NIH was recently accused of funding research of a paper that had images of sedated puppies with their heads inserted into small enclosures containing disease carrying sand flies. So I can just say that this story is not true, or at least the... I think it is true that the paper that showed those images cited NIH as a funding source, but that citation is not correct. That was not correct. Yeah. But that brings up a bigger philosophical question, that it could have been correct. How difficult is it as a director of NIH or just NIH as an organization that's funding so many amazing deep research studies to ensure the ethical fortitude of those studies when the ethics of science is... There's such a gray area between what is and what isn't ethical. Well, tough issues. Certainly animal research is a tough issue. I was going to bring up as a good example of that tough issue is in 2015, you announced that NIH will no longer support any biomedical research involving chimpanzees. So that's like one example of looking in the mirror, thinking deeply about what is and isn't ethical. And there was a conclusion that biomedical research on chimps is not ethical. That was the conclusion. That was based on a lot of deep thinking and a lot of input from people who have considered this issue and a panel of the National Academy of Sciences that was asked to review the issue. I mean, the question that I wanted them to look at was, are we actually learning anything that's really essential from chimpanzee invasive research at this point? Or is it time to say that these closest relatives of ours should not be subjected to that any further and ought to be retired to a sanctuary? And that was the conclusion that there was really no kind of medical experimentation that needed to be done on chimps in order to proceed. So why are we still doing this? Many of these were chimpanzees that were purchased because we thought they would be good hosts for HIV AIDS, and they sort of weren't. And they were kept around in these primate laboratories with people coming up with other things to do, but they weren't compelling scientifically. So I think that was the right decision. I took a lot of flak from some of the scientific community said, well, you're caving in to the animal rights people. And now that you've said no more research on chimps, what's next? Certainly when it comes to companion animals, everybody's heart starts to be hurting when you see anything done that seems harmful to a dog or a cat. I have a cat, I don't have a dog. And I understand that completely. That's why we have these oversight groups that decide before you do any of that kind of research, is it justified? And what kind of provision is going to be made to avoid pain and suffering? And those have input from the public as well as the scientific community. Is that completely saying that every step that's happening there is ethical by some standard that would be hard for anybody to agree to? No, but at least it's a consensus of what people think is acceptable. Dogs are the only host for some diseases like leishmaniasis, which was that paper that we were not responsible for, but I know why they were doing the experiment, or like lymphatic filariasis, which is an experiment that we are supporting in Georgia that involves dogs getting infected with a parasite, because that's the only model we have to know whether a treatment is going to work or not. So I will defend that. I am not in the place of those who think all animal research is evil, because I think if there's something that's going to be done to save a child from a terrible disease or an adult, and it involves animal research that's been carefully reviewed, then I think ethically why it doesn't make me comfortable, it still seems like it's the right choice. I think to say all animal research should be taken off the table is also very unethical, because that means you have basically doomed a lot of people for whom that research might have saved their lives to having no more hope. And to me personally, there's far greater concerns ethically in terms of factory farming, for example, the treatment of animals in other contexts. There's so much that goes on outside of medical research that is much more troubling. That said, I think all cats have to go. That's just my off the record opinion. That's why I'm not involved with any ethical decisions. I'm just joking internet ethic. I love cats. You're a dog person. I'm a dog person. I'm sorry. Have you seen the New Yorker cartoon where there are two dogs in the bar having a martini and one is saying they're dressed up in their business suits and one says to the other, you know, it's not enough for the dogs to win. The cats have to lose. That's beautiful. So a few weeks ago, you've announced that you're resigning from the NIH at the end of the year. I'm stepping down. I'm still going to be at NIH at a different capacity. Right. And it's over a decade of an incredible career overseeing the NIH as its director. What are the things you're most proud of, of the NIH in your time here as its director may be memorable moments? There's a lot in 12 years. Science has just progressed in amazing ways over those 12 years. Think about where we are right now. Something like gene editing, being able to make changes in DNA, even for therapeutic purposes, which is now curing sickle cell disease. Unthinkable when I became director in 2009. The ability to study single cells and ask them what they're doing and get an answer. Single cell biology just has emerged in this incredibly powerful way. Having the courage to be able to say we could actually understand the human brain seemed like so far out there. And we're in the process of doing that with the Brain Initiative.

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