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課程來源:TED
     

 

Anthony Atala 談列印人類腎臟

Anthony Atala: Printing a human kidney

 

Photo of three lions hunting on the Serengeti.

講者:Anthony Atala

2011年3月演講,2011年3月在TED2011上線

 

翻譯:TED

編輯:朱學恆、洪曉慧

簡繁轉換:洪曉慧

後製:洪曉慧

字幕影片後制:謝旻均

 

影片請按此下載

MAC及手持裝置版本請按此下載

閱讀中文字幕純文字版本

 

關於這場演講

外科醫師Anthony Atala展示了一項未來可能用以解決器官捐贈問題的實驗初期成果:一台使用活細胞輸出可移植腎臟的3D印表機。十年前,Atala醫師的年輕病人Luke Massella接受了以類似科技製造的膀胱移植手術。Luke Massella本人亦會出現在講台上。

 

關於Anthony Atala

Anthony Atala問,「我們能以器官培養代替器官移植嗎?」他在Wake Forest再生醫學研究所的實驗室正進行的工作是培養30多種組織和完整器官。

 

為什麼要聽他演講

Anthony Atala是Wake Forest再生醫學研究所主任,他的工作重點是培養組織和器官,並使其再生。他的團隊製造出第一個由實驗室培養而移植到人體內的膀胱,目前正開發可「列印」人體所需組織的製造技術。

 

2007年,Atala和哈佛大學研究團隊證實可從孕婦羊水中獲取幹細胞。這個成果及其他在開發智慧生物材料和組織製造技術上的突破,有望為醫學上的實際應用帶來革命性成果。

 

「Anthony Atala烘培的東西會讓你身體健康,但我們指的不是蛋糕和鬆餅。」

-美國公共電視台

 

Anthony Atala的英語網上資料

Website: Wake Forest Institute for Regenerative Medicine

 

[TED科技‧娛樂‧設計]

已有中譯字幕的TED影片目錄(繁體)(簡體)。請注意繁簡目錄是不一樣的。

 

Anthony Atala 談列印人類腎臟

現今其實存在著一個重大的醫療健康危機,那就是器官短缺。事實上,我們活得更長久了,現代醫學對於讓我們活得更長久居功厥偉。問題是:當我們老化時,我們器官衰竭的機率也增加,因此現今可供使用的器官並不足夠。事實上,過去十年間需要器官移植的病人數量倍增,但同時,真正進行的器官移植手術卻幾乎沒有增加,因此,現在這已是公眾健康危機。

 

因此,這就是我們進行所謂再生醫學這個領域研究的原因,它其實牽涉了許多不同領域,你可以使用,例如:支架、生物材料,它們就像襯衫或上衣上的一塊布料,但這些是真正可以植入病人體內的專門材料,它們無害地在你體內,協助組織再生,或我們可以單獨使用細胞,不論是你本身的細胞或不同的幹細胞群,或兩者兼用。事實上,我們可以將生物材料與細胞一起使用,這就是今日這個領域的現況。

 

但事實上,這並不是一個新興的領域,有趣的是,這裡有一本1938年出版的書,書名是《器官培養》,第一作者是一名諾貝爾獎得主Alexis Carrel,他事實上發明了一些今日縫合血管仍在使用的技術,我們今日使用的某些血管嫁接法就是Alexis設計的。但我想要你們注意一下他的共同作者:查爾斯‧林白,就是那個飛越大西洋的林白,他後半輩子都跟Alexis一起,在紐約的洛克斐勒醫學研究所(現為洛克斐勒大學)進行器官培養研究。

 

那麼,如果這個領域已經存在了這麼多年,為什麼臨床的突破這麼少?這其實跟許多不同的難題有關,但如果要我列出三大難題,第一個將會是材料的設計,一個能夠進入你身體且長時間穩定無害的材料。現今這方面已有許多進展,我們可以相當迅速地做到這點。第二個難題是細胞,我們無法獲得足量的病人細胞在體外進行培養,過去二十年間,基本上我們克服了這個難題,許多科學家現在可以培養許多不同種類的細胞-更何況我們還有幹細胞,但就算是現在,2011年,仍然有某些特定細胞就是無法從病人身上培養:肝細胞,神經細胞,胰細胞。即使在今天,我們仍然無法培養它們。第三個難題是血管結構,能夠真正將血液供給這些器官或組織,讓它們再生後得以存活。

 

現在我們已經可以使用生物材料了,這就是生物材料,我們可以將它們編織、接合,或將它們做成你眼中所見的這樣。這其實像台棉花糖機,你們看到,水花噴進去,就像棉花糖的細絲組成了這個結構,這個管狀結構,這就是接下來我們可以用來幫助你身體再生的生物材料,使用的原料是你自身的細胞,這就是我們所做的。

 

這是一位病人,他某個器官病變壞死了,我們製造出這些智慧型生物材料,並用這些智慧型材料來取代並修復病人自身的結構。我們事實上使用生物材料來當做橋樑,因此器官內的細胞可以在橋樑上走動,然後幫忙跨越缺口,使組織再生。你們在這裡看到的是,這位病患經治療後六個月,他的X光片顯示的是再生的組織,當你在顯微鏡下仔細觀察後,可以發現它已經完全再生了。我們也可以只用細胞,這些是我們獲得的細胞,這些是我們從特定來源製造出的幹細胞,我們可以使它們成為心臟細胞,接著它們在培養基中開始跳動,因此它們知道該做什麼,細胞們經由遺傳而知道該做什麼,然後它們開始一起跳動。今日,許多臨床試驗,使用不同種類的幹細胞來治療心臟疾病,因此這個方法事實上已在病人身上使用。

 

或者,如果我們打算使用更大型結構來替換更大的結構,我們可以使用病人自身的細胞,或一部分細胞群、生物材料和支架構造等一起使用。所以,這裡的概念是:如果你的器官生病或受損,我們從其上取下一片非常小的組織,比半張郵票還小,然後我們分離這些細胞,並在體外做培養,然後我們拿一個用生物材料製成的支架,同樣的,看起來就像你們襯衫或上衣的一小片布料,然後我們使用這個材質來塑型,使用這些細胞包覆這個物質,一次一層,就像烘培千層糕一樣,然後我們將它放入一個類似烤箱的裝置中,就能創造出這結構,並將它取出。這是我們製造的一個心臟瓣膜,你在這裡可以看到,我們有心臟瓣膜的結構,我們在其上種滿了細胞,然後讓它運動,所以你可以看到,這些心臟瓣膜的葉瓣不斷開合。這個心臟瓣膜還在實驗階段,我們試著用它來做進一步研究。

 

另一個我們已在病人身上實際使用的科技,事實上與膀胱有關。我們從病人身上取下一片非常小的膀胱組織,比半張郵票還小,然後在體外培養這些細胞,取用支架並以細胞包覆。這些細胞來自病人自身,是兩種不同類型的細胞,然後將它放入這個類似烤箱的裝置,裝置內的環境條件與人體內部相同,攝氏35度,含氧量95%。數周後,你就得到一個可以移植回病人身上的人工器官。對這些特定的病人來說,我們事實上只是將這些材料接合起來,使用了3D影像分析技術。事實上,我們用手工製作這些生物材料。

 

但我們現在有更好的方法,可利用細胞來製造這些結構。我們現在使用某種科技,舉例來說,對於實心臟器,像是肝臟,我們取用廢棄的肝臟。如你所知,很多器官事實上是廢棄、沒被使用的,所以我們能夠取用這些廢棄不用的肝臟結構,將其放入類似洗衣機的裝置,將肝細胞洗掉,兩週後,你就得到了某種看似肝臟的東西。你將它捧在手心,感覺就是個肝臟,但它不含任何細胞,它只是肝臟的骨架,然後我們可以重新將細胞散佈在肝臟上,保存血管的樹狀結構。事實上,我們先將血管的樹狀結構浸置在病人自己的血管細胞中,然後將肝臟細胞滲透到薄壁組織中,現在我們能夠展示過去一個月使用這種科技創造人類肝臟組織的成果。

 

我們所使用的另一項科技,事實上是列印器官。這是一個桌上型噴墨印表機,但並非使用墨水匣,而是使用細胞。你可以看到它的噴頭正在運作,並列印出這個構造,印出整個構造大約要花四十分鐘,這裡有個3D升降台,每次噴頭經過的時候,它會同時下降一層,最後,你將可以得到這整個結構,你可以輕易地將這個構造從印表機上取下,並做移植。這是一小塊骨頭,我會在這張投影片中展示給你們看,這是使用桌上型印表機製造的。如你們所見,將其做移植,所有被移植的新骨骼都是用這些科技製造的。

 

另一個我們正在研究的、更先進的技術,我們的新一代科技,是更複雜的印表機。這個我們目前正在設計的特殊印表機,將會直接在病人身體上列印,因此,你們在這裡看到的,我知道聽起來很可笑,但這就是它運作的方式。因為在現實生活中,你會希望當病人受傷躺在病床上時,你能有個掃描器,基本上就像個平板掃描器,就是你在右邊看到的。你所見的是掃描技術,首先掃描病人的傷口,然後回過頭來變成噴頭,直接在病人身上列印出你需要的組織層。

 

這就是它運作的方式。這是掃描器掃描傷口的過程,一旦掃描完成,它就將訊息轉換成正確的細胞層,並列印在所需之處。現在你們將看到一段在一個代表性傷口上的真實操作示範,我們實際上使用的是凝膠,因此你可以將這個膠狀材質剝下,一旦這些細胞被列印在病人身上,它們將會附著在它們應該在的位置。事實上,這是一項仍在開發中的新科技。

 

我們也正在研發更複雜的印表機,因為在現實世界中,我們最大的難題是實心器官。我不知道你們是否瞭解這點,但器官移植等待名單上,90%的病人事實上是在等待腎臟。每天都有病患過世,因為我們沒有足夠的器官可用,因此這是一個比大型器官、血管更大的難題。這器官有很多血管供血和很多的血管細胞,因此我們的策略是-這是電腦斷層掃描,一張X光片,我們將它一層層堆疊起來,使用電腦化形態影像分析,重建其3D影像,來獲得病人腎臟的資訊。我們能真正描繪出這個影像,並將其做360度旋轉,分析這個腎臟,全方位研究其空間上的特性,然後我們就能使用這些資訊,以電腦化的輸出格式來掃描這個腎臟。我們一層層檢視這個器官,仔細分析每一層構造,然後我們可以將這些資訊送到,如你這裡所見,送入電腦,並為病人設計器官。這是印表機實體,這是正在列印的實況。

 

事實上,我們將印表機帶到現場來了,所以我們今天演講的時候,你們可以真正看到印表機,就在這裡的後台。這就是我們帶來的印表機實機,它正在列印,你們在這裡看到的是腎臟構造,列印出一個腎臟約費時七小時,這個大概已經列印三小時了。Kang博士現在正走上講台,我們將要給你們看一顆列印出來的腎臟,是今天稍早時列印出來的,讓我戴上手套,這些列印出的腎臟是正研究中的初期原型,仍需數年時間才可做臨床上使用。這些手套對我來說有點小,但就是這顆腎臟,你們可以看到這顆今天稍早列印出來的腎臟。

 

(掌聲)

 

還有一點黏。這是參與我們這項研究計畫的Kang博士,他是團隊的一份子,謝謝你,Kang博士,我非常感激。

 

(掌聲)

 

事實上,這是新一代機種,就是你們在講台上看到的印表機,也是我們目前正在研究的新科技。事實上,我們研究這個的歷史已經很久了,我將要跟你們分享一段影片,關於我們已在病人身上應用了一段時間的科技。

 

這是一段非常短的影片,大約只有卅秒,關於一位真正移植了這種器官的病人。

 

(影片)Luke Massella:我曾病得很重,幾乎無法下床,無法去上學,這真的很悲慘。我無法出門,下課時,只要打籃球就會覺得快要昏倒,回到教室後會覺得非常不舒服。我所面對的,基本上是終生血液透析治療,我甚至不想思考未來會是怎樣,如果我一輩子都這樣的話。因此對我來說,接受手術後,生命美好多了。我能做更多的事,高中時我甚至能練習摔角,還成了摔角隊長,真棒!我能像個正常小孩般跟朋友相處,因為醫生們用我自己的細胞來建造這個膀胱,它將會一輩子伴隨著我,所以一切都沒問題了。

 

(掌聲)

 

Juan Enriquez:這些實驗有時候能夠成功,當它們真的成功時是非常酷的,Luke,請到台上。

 

(掌聲)

 

Luke,昨天晚上之前,你最後一次與Tony醫師見面是什麼時候?

 

LM: 十年前,當我動手術的時候,能再見面真的很棒。

 

(笑聲)

 

(掌聲)

 

JE: 跟我們談談你現在在做什麼?

 

LM: 我現在是康乃狄克大學的學生,現在大二,主修大眾傳播、電視與媒體,基本上試著像正常孩子般生活,那是我一直希望長大的方式。但當時很難做到,因為我有先天性脊柱分裂症,我的腎臟與膀胱皆無法作用,我經歷了約16場手術,似乎依然毫無希望。我十歲時腎臟就已經衰竭,直到動了這個手術,基本上它造就了今天的我,拯救了我的生命。

 

(掌聲)

 

JE:而且Tony醫師完成了上百起這種手術?

 

LM: 就我所知,他在實驗室裡非常努力工作,想出些瘋狂的發明,我知道我是前十位進行這類手術的人,但我十歲的時候並不明白這有多了不起,我只是個小孩子,當時心裡的想法就像這樣,「對,我要,我要動這個手術。」(笑聲)我只想改善我的健康,但我並不明白這手術有多偉大,直到我大了些,才瞭解他所從事工作的偉大之處。

 

JE: 當你突然接到這通電話,Tony很害羞,我們花了很多時間才說服像Tony這麼謙虛的人,允許我們將Luke帶來這裡。那麼,Luke,當你去跟你的傳播教授,你主修傳播,當你徵求他們同意來參加TED時,也許這跟傳播有點關係,他們的反應是什麼?

 

LM: 大多數老師們都全力支持,他們說:「記得帶相片回來,跟我分享網路上的影片。」以及「我為你感到高興。」有幾個教授有點固執,但我仍然得跟他們溝通,終於讓他們答應。

 

JE:與你見面是我的榮幸,非常謝謝你。(LM: 非常謝謝你)

 

JE: 謝謝你,Tony。

 

(掌聲)

 

以下為系統擷取之英文原文

About this Talk

Surgeon Anthony Atala demonstrates an early-stage experiment that could someday solve the organ-donor problem: a 3D printer that uses living cells to output a transplantable kidney. Using similar technology, Dr. Atala's young patient Luke Massella received an engineered bladder 10 years ago; we meet him onstage.

About the Speaker

Anthony Atala asks, "Can we grow organs instead of transplanting them?" His lab at the Wake Forest Institute for Regenerative Medicine is doing just that -- engineering over 30 tissues and whole… Full bio and more links  

Transcript

There's actually a major health crisis today in terms of the shortage of organs. The fact is that we're living longer. Medicine has done a much better job of making us live longer. And the problem is, as we age, our organs tend to fail more. And so currently there are not enough organs to go around. In fact, in the last 10 years, the number of patients requiring an organ has doubled, while in the same time, the actual number of transplants has barely gone up. So this is now a public health crisis.

So that's where this field comes in that we call the field of regenerative medicine. It really involves many different areas. You can use, actually, scaffolds, biomaterials -- they're like the piece of your blouse or your shirt -- but specific materials you can actually implant in patients and they will do well and help you regenerate. Or we can use cells alone, either your very own cells or different stem cell populations. Or we can use both; we can use, actually, biomaterials and the cells together. And that's where the field is today.

But it's actually not a new field. Interestingly, this is a book that was published back in 1938. It's titled "The Culture of Organs." The first author, Alexis Carrel, a Nobel Prize winner. He actually devised some of the same technologies used today for suturing blood vessels. And some of the blood vessel grafts we use today were actually designed by Alexis. But I want you to note his co-author: Charles Lindbergh. That's the same Charles Lindbergh who actually spent the rest of his life working with Alexis at the Rockefeller Institute in New York in the area of the culture of organs.

So if the field's been around for so long, why so few clinical advances? And that really has to do to many different challenges. But if I were to point to three challenges, the first one is actually the design of materials that could go in your body and do well over time. And many advances now, we can do that fairly readily. The second challenge was cells. We could not get enough of your cells to grow outside of your body. Over the last 20 years, we've basically tackled that. Many scientists can now grow many different types of cells -- plus we have stem cells. But even now, 2011, there's still certain cells that we just can't grow from the patient. Liver cells, nerve cells, pancreatic cells -- we still can't grow them even today. And the third challenge is vascularity, the actual supply of blood to allow those organs or tissues to survive once we regenerate them.

So we can actually use biomaterials now. This is actually a biomaterial. We can weave them, knit them, or we can make them like you see here. This is actually like a cotton candy machine. You saw the spray going in. That was like the fibers of the cotton candy creating this structure, this tubularized structure, which is a biomaterial that we can then use to help your body regenerate using your very own cells to do so. And that's exactly what we did here.

This is actually a patient who presented with a deceased organ, and we then created one of these smart biomaterials, and then we then used that smart biomaterial to replace and repair that patient's structure. What we did was we actually used the biomaterial as a bridge so that the cells in the organ could walk on that bridge, if you will, and help to bridge the gap to regenerate that tissue. And you see that patient now six months after with an X-ray showing you the regenerated tissue, which is fully regenerated when you analyze it under the microscope. We can also use cells alone. These are actually cells that we obtained. These are stem cells that we create from specific sources, and we can drive them to become heart cells. And they start beating in culture. So they know what to do. The cells genetically know what to do, and they start beating together. Now today, many clinical trials are using different kinds of stem cells for heart disease. So that's actually now in patients.

Or if we're going to use larger structures to replace larger structures, we can then use the patient's own cells, or some cell population, and the biomaterials, the scaffolds, together. So the concept here: so if you do have a deceased or injured organ, we take a very small piece of that tissue, less than half the size of a postage stamp. We then tease the cells apart, we grow the cells outside the body. We then take a scaffold, a biomaterial, again, looks very much like a piece of your blouse or your shirt. We then shape that material, and we then use those cells to coat that material one layer at a time -- very much like baking a layer cake, if you will. We then place it in an oven-like device, and we're able to create that structure and bring it out. This is actually a heart valve that we've engineered. And you can see here, we have the structure of the heart valve and we've seeded that with cells, and then we exercise it. So you see the leaflets opening and closing -- of this heart valve that's currently being used experimentally to try to get it to further studies.

Another technology that we have used in patients actually involves bladders. We actually take a very small piece of the bladder from the patient -- less than half the size of a postage stamp. We then grow the cells outside the body, take the scaffold, coat the scaffold with the cells -- the patient's own cells, two different cell types. We then put it in this oven-like device. It has the same conditions as the human body -- 37 degrees centigrade, 95 percent oxygen. A few weeks later, you have your engineered organ that we're able to implant back into the patient. For these specific patients, we actually just suture these materials. We use three-dimensional imagining analysis, but we actually created these biomaterials by hand.

But we now have better ways to create these structures with the cells. We use now some type of technologies, where for solid organs, for example, like the liver, what we do is we take discard livers. As you know, a lot of organs are actually discarded, not used. So we can take these liver structures, which are not going to be used, and we then put them in a washing machine-like structure that will allow the cells to be washed away. Two weeks later, you have something that looks like a liver. You can hold it like a liver, but it has no cells; it's just a skeleton of the liver. And we then can re-perfuse the liver with cells, preserving the blood vessel tree. So we actually perfuse first the blood vessel tree with the patient's own blood vessel cells, and we then infiltrate the parenchyma with the liver cells. And we now have been able just to show the creation of human liver tissue just this past month using this technology.

Another technology that we've used is actually that of printing. This is actually a desktop inkjet printer, but instead of using ink, we're using cells. And you can actually see here the printhead going through and printing this structure, and it takes about 40 minutes to print this structure. And there's a 3D elevator that then actually goes down one layer at a time each time the printhead goes through. And then finally you're able to get that structure out. You can pop that structure out of the printer and implant it. And this is actually a piece of bone that I'm going to show you in this slide that was actually created with a desktop printer and implanted as you see here. That was all new bone that was implanted using these techniques.

Another more advanced technology we're looking at right now, our next generation of technologies, are more sophisticated printers. This particular printer we're designing now is actually one where we print right on the patient. So what you see here -- I know it sounds funny, but that's the way it works. Because in reality, what you want to do is you actually want to have the patient on the bed with the wound, and you have a scanner, basically like a flatbed scanner. That's what you see here on the right side; you see a scanner technology that first scans the wound on the patient and then it comes back with the printheads actually printing the layers that you require on the patients themselves.

This is how it actually works. Here's the scanner going through scanning the wound. Once it's scanned, it sends information in the correct layers of cells where they need to be. And now you're going to see here a demo of this actually being done in a representative wound. And we actually do this with a gel, so that you can lift the gel material. So once those cells are on the patient they will stick where they need to be. And this is actually new technology still under development.

We're also working on more sophisticated printers. Because in reality, our biggest challenge are the solid organs. I don't know if you realize this, but 90 percent of the patients on the transplant list are actually waiting for a kidney. Patients are dying every day because we don't have enough of those organs to go around. So this is more challenging -- large organ, vascular, a lot of blood vessel supply, a lot of cells present. So the strategy here is -- this is actually a CT scan, an X-ray -- and we go layer by layer, using computerized morphometric imaging analysis and 3D reconstruction to get right down to those patient's own kidneys. We then are able to actually image those, do 360 degree rotation to analyze the kidney in its full volumetric characteristics, and we then are able to actually take this information and then scan this in a printing computerized form. So we go layer by layer through the organ, analyzing each layer as we go through the organ. And we then are able to send that information, as you see here, through the computer and actually design the organ for the patient. This actually shows the actual printer. And this actually shows that printing.

In fact, we actually have the printer right here. So while we've been talking today, you can actually see the printer back here in the back stage. That's actually the actual printer right now, and that's been printing this kidney structure that you see here. It takes about seven hours to print a kidney, so this is about three hours into it now. And Dr. Kang's going to walk onstage right now, and we're actually going to show you one of these kidneys that we printed a little bit earlier today. Put on a pair of gloves here. Thank you. Go backwards. So, these gloves are a little bit small on me, but here it is. You can actually see that kidney as it was printed earlier today.

(Applause)

Has a little bit of inconsistency to it. This is Dr. Kang who's been working with us on this project, and part of our team. Thank you, Dr. Kang. I appreciate it.

(Applause)

So this is actually a new generation. This is actually the printer that you see here onstage. And this is actually a new technology we're working on now. In reality, we now have a long history of doing this. I'm going to share with you a clip in terms of technology we have had in patients now for a while.

And this is actually a very brief clip -- only about 30 seconds -- of a patient who actually received an organ.

(Video) Luke Massella: I was really sick. I could barely get out of bed. I was missing school. It was pretty much miserable. I couldn't go out and play basketball at recess without feeling like I was going to pass out when I got back inside. I felt so sick. I was facing basically a lifetime of dialysis, and I don't even like to think about what my life would be like if I was on that. So after the surgery, life got a lot better for me. I was able to do more things. I was able to wrestle in high school. I became the captain of the team, and that was great. I was able to be a normal kid with my friends. And because they used my own cells to build this bladder, it's going to be with me. I've got it for life, so I'm all set.

(Applause)

Juan Enriquez: These experiments sometimes work, and it's very cool when they do. Luke, come up please.

(Applause)

So Luke, before last night, when's the last time you saw Tony?

LM: 10 years ago, when I had my surgery -- and it's really great to see him.

(Laughter)

(Applause)

JE: And tell us a little bit about what you're doing.

LM: Well right now I'm in college at the University of Connecticut. I'm a sophomore and studying communications, TV and mass media. And basically trying to live life like a normal kid, which I always wanted growing up. But it was hard to do that when I was born with spina bifida and my kidneys and bladder weren't working. I went through about 16 surgeries, and it seemed impossible to do that when I was in kidney failure when I was 10. And this surgery came along and basically made me who I am today and saved my life.

(Applause)

JE: And Tony's done hundreds of these?

LM: What I know from, he's working really hard in his lab and coming up with crazy stuff. I know I was one of the first 10 people to have this surgery. And when I was 10, I didn't realize how amazing it was. I was a little kid, and I was like, "Yeah. I'll have that. I'll have that surgery." (Laughter) All I wanted to do was to get better, and I didn't realize how amazing it was until now that I'm older and I see the amazing things that he's doing.

JE: When you got this call out of the blue -- Tony's really shy, and it took a lot of convincing to get somebody as modest as Tony to allow us to bring Luke. So Luke, you go to your communications professors -- you're majoring in communications -- and you ask them for permission to come to TED, which might have a little bit to do with communications, and what was their reaction?

LM: Most of my professors were all for it, and they said, "Bring pictures and show me the clips online," and "I'm happy for you." There were a couple that were a little stubborn, but I had to talk to them. I pulled them aside.

JE: Well, it's an honor and a privilege to meet you. Thank you so much. (LM: Thank you so much.)

JE: Thank you, Tony.

(Applause)
 


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