2020年12月25日，
京領榜單發布會暨諾獎創新論壇發布了
《2020中國國際學校競爭力排行榜》
《2020中國國際化學校品牌價值百強榜》
《2020中國國際學校創新競爭力百強榜》
並且共邀請了五位主旨演講嘉賓：諾貝爾經濟學獎得主、哈佛大學校級教授馬斯金教授；北京一零一中（教育集團）校長、國家督學陸雲泉；劍橋大學終身正教授、院士卡德維爾教授；諾貝爾物理學獎得主巴裡什教授；諾貝爾諾貝爾生理或醫學獎得主謝克曼教授參與京領榜單發布會暨諾獎創新論壇，並在與會嘉賓共同見證下重磅發布2020中國國際學校系列排行榜。
諾貝爾生理或醫學獎得主、美國國家科學院院士
蘭迪·謝克曼（Randy Scheckman）
受邀在論壇上發表了精彩演講。
嘉賓介紹
謝克曼教授
諾貝爾生理或醫學獎得主
美國國家科學院院刊前主編
美國國家科學院院士
美國藝術與科學院院士
謝克曼教授是世界知名生物化學家和細胞生物學家，美國國家科學院院士，美國藝術與科學院院士。2013年，基於在細胞膜囊泡運輸方面開創性的貢獻，謝克曼教授與詹姆斯·羅思曼和託馬斯·聚德霍夫共同獲得諾貝爾生理學或醫學獎。謝克曼教授還是美國細胞生物學學會2010年E. B.威爾遜獎、2011年亞瑟·科恩伯格和保羅·伯格終身成就獎、德國生物化學學會奧託·沃伯格獎的獲得者。謝克曼教授積極倡導呼籲學術期刊出版改革和開放獲取科學出版物，並擔任由霍華德·休斯醫學研究所、馬克斯·普朗克學會、惠康基金會聯合發布的開放獲取期刊《eLife》的編輯。
謝克曼教授作為諾貝爾生理或醫學獎得主、世界知名生物化學家和細胞生物學家，美國國家科學院院士，美國藝術與科學院院士，在本次論壇中進行了深刻的發言，闡釋了基礎科學在創新中的重要性。
京領在此獨家放送謝克曼教授的精彩演講，以饗讀者。
以下是謝克曼教授的演講內容：
瀏覽器版本過低，暫不支持視頻播放
01
大家好，歡迎來到京領榜單發布會暨諾獎創新論壇，我是Randy Scheckman，加州大學伯克利分校細胞生物學系的教授，我要歡迎我中國的朋友們、理工科的學生們、有抱負的年輕醫學博士和他們的家庭成員們。因為今天我想要簡單的講述一下，為什麼我覺得基礎科學對過程的基本理解如此重要。
比如我的案例提到的是細胞是怎麼工作的，這能引導我們從大方向了解我們所面對的問題，比如我們現在正在遭受的流行病以及衰弱性疾病，如神經退行性疾病，等下我會專門討論一個的例子。
但在我講述之前，我想先描述一下我的發現之路來引導大家理解，我想說明的基礎科學的重要性。
當我在加州成長的時候，我開始對微生物感興趣。我感興趣是因為我那會有一個顯微鏡，我是通過我自己在周圍鄰居附近幫忙幹活掙得錢買的，那是我高中時期一個博世倫的學生顯微鏡，我一直用它研究當地科學展會的項目。但我上大學的時候就把這個顯微鏡閒置了，再後來我就成為了加州大學伯克利分校的一名教職員工，並且我有繼續研究微生物學。因為我覺得了解簡單的有機體有助於我們探索更有難度的、和更複雜的有機體問題。
02
讓我來通過展示酵母細胞的圖片來給大家說明我的觀點。
這些是用來烤麵包和發酵酒精的細胞，但它們是可以幫助我們理解基本生命過程的強大實驗有機體，因為就像大家看到的，酵母細胞使用的是與人類細胞製造蛋白質分子一樣的過程機制，就是把它們打包並運輸到細胞外，這個過程叫做蛋白質分泌，這對於我們身體裡的每一個細胞都很重要。因為它們負責組織運送進入血液和進入淋巴系統，抗體分子以及胰島素之類的激素裡的蛋白質。這些全部都要被打包進細胞裡，然後再運輸到細胞外，所以我決定在麵包酵母中研究這個過程，因為我相信它最終會和人類細胞共享相同的機制。
然而，從之前到現在，研究一個可以在實驗室大量生長的有機體都要簡單得多，而且也可以對它們進行簡單的基因操作。
這是一個生長在葡萄表面的v簇細胞，當酵母細胞生長和分裂時，它就會從發芽開始它的生命，然後它的芽會越長越大，酵母細胞就會在90分鐘左右的時間裡分裂，最終芽會變的和母細胞一樣大，然後細胞就會分裂成兩半。如果培養基因中的營養條件良好，細胞就會繼續這樣，然後再多代中呈指數增長。
如果你看看酵母細胞的內部，會看到一些可以表明它和其他細胞一樣的證據。
這些點叫做核糖體，它們就像縫紉機般的小機器一樣把胺基酸縫合在一起形成蛋白質。但細胞中也有內膜，其中有一些非常類似於在人體細胞中看到的薄片。我們要注意的是這些叫做血管的小膜，我們在遺傳實驗和生化實驗中都有呈現出，這些血管可以捕獲細胞外分泌的，可以讓它生長在葡萄表面的蛋白質。
現在我們從多年的工作中發現酵母細胞用來組織這個過程的基因也和我們體內的細胞做這個過程的基因是相同的，甚至與胰島素這樣製造和分泌的分子都一樣，這也讓酵母細胞有可能成為組織臨床上重要蛋白質生殖和分泌的一個平臺。
就比如說現在全球三分之一供應用來治療糖尿病的重組胰島素都是在巨大的發酵罐中製造的，成千上萬的領導者在成長過程中把胰島素分泌到這種生長介質中，然後從中分離出胰島素並用於治療糖尿病患者。
酵母細胞也可以用來製造我們使用的疫苗。像你們接種的B肝疫苗在中國曾是一種可怕的傳染病，世界上90%的肝癌都是由B肝引起的，現在都可以有效地通過酵母顆粒進行免疫。因為我們的發現，或許它們也會在更廣泛的臨床環境中得到應用。
03
七年前，我也因此獲得了諾貝爾獎,你們可以看見照片裡我在斯特哥爾摩從瑞典國王手中接過證書，這是七年前的12月份了。
恰恰就在頒獎典禮之前，我向斯特哥爾摩的諾貝爾博物館捐獻了那個開啟我科學之旅的顯微鏡。如果你們有機會去斯德哥爾摩，你們可以去看看我的那個顯微鏡，那還描述了這個顯微鏡在我對科學產生興趣的過程中起了多麼重要的作用。
04
現在我要說另一個話題，不過邏輯是相同的，這就是基礎科學在理解像帕金森氏症候群等複雜疾病方面的重要性。
你們可能會認識帕金森的患者，它通常結合著行動困難或有時有語言障礙或咳嗽困難等症狀，它通常伴隨著認知功能的衰退和發展性痴呆症，這是一種非常嚴重的疾病，它可以持續發展很多年，並且有不可避免的致命性。當人們患上帕金森時會有各種各樣的死亡原因，然而我們還不了解這種疾病的根本原因，我想跟你們講講我們知道的一點事情，以及我如何努力來獲得這種疾病的分子和細胞。
首先，這種疾病在世界範圍內都影響深遠。這是一種流行病，和我們現在遭受的流行性新冠病毒沒什麼不同，但有一個區別就是，新冠病毒在之後的幾年中肯定會因為疫苗的誕生被控制住，但帕金森會一直持續著，甚至是變得更加具有普遍性，數百萬的患者都在遭受這種疾病。
據估計，在未來的十年左右，全世界將有近2000萬人患上這種疾病，這種病雖然大部分都是因為老齡化，但並非全部都是因此。事實上，這種疾病不分國界，就像冠狀病毒大流行一樣。我要特別提醒你們，現在幾乎有一半，並且在將來將會有超過一半以上的帕金森患者都會在你們國家，因此這是一個至關重要的問題，無論對於中國政府還是世界政府都要試圖了解以及開發出更好的治療方法。
現在我來告訴大家一些我們已知的成果和相關問題。200年前，這種疾病最初被認為是運動障礙，直到近100年來，這種疾病才被理解為是大腦內某個區域無法分泌出多巴胺這種化學物質而導致的。多巴胺是使神經細胞能夠進行互相交流的物質，同時控制人體肌肉運動以及其他的情緒和認知能力。
看一下現在圖中大腦的這一區域。因為其他原因死亡的人的大腦這部分區域是這樣的在這一區域內，你可以看到在中腦有一小條黑帶，這一部分被黑色素的存在突顯了出來。這些黑色素由黑色素細胞構成，可以看到因為其他原因死亡的人的大腦這部分區域是這樣的，然而在因患帕金森而死亡的人的大腦中，那條由黑色素構成的黑帶大部分都消失了。那是因為在死亡的時候，那些黑色素細胞早就死亡了。
事實上，當某人出現早期帕金森的症狀時，腦中有將近一半的黑色素細胞都已經死亡了，並且剩餘的細胞還會繼續死亡。目前為止，沒有任何方法有助於控制黑色素細胞死亡。
一百年前左右,另一個名為路易（Frederick Lewy）的英國醫生觀察了大腦有這一區域有帶狀痕跡的帕金森患者的歷史情況。他看到一些細胞是黑色的，現在那些細胞被稱為路易氏體，那些似乎是損壞的蛋白質和膜的堆積，並且也許那就是這些細胞死亡的原因，或者是細胞和膜累積在一起只是細胞正在死亡的症狀之一。
我們不知道是否是這樣，不知道這樣的症狀是什麼原因導致的，也不知道如何阻止這樣的症狀發生，因此，我們中的許多人共同研究了這些基本過程，我們可以在實驗室培養生長這些大腦裡的細胞。這是一個動畫版的神經細胞，我們怎麼來研究這些細胞呢？我們需要怎麼樣來了解帕金森這個疾病呢？
05
幾年前，我同意領導一項叫做跨帕金森症的科學調整工作。這個項目是從美國開始的，現在變得越來越國際化。
我們召集了來自11個國家的調查人員團隊和近100個不同的實驗室，這些團隊都共同從事研究同一主題，這樣才可以幫助我們發現疾病的根本所在。我們還和一個組織一起研究，這個組織是美國的Michael J Fox基金會，我們在跨越國界，使人們參與協作其中，因為這不是某一個實驗室就能解決的問題。
因此，你可以把這種疾病視為一個拼圖，一個包括很多碎片的拼圖，就像這只是一個有著少量碎片信息的拼圖，但僅通過這些現有的碎片就能看出來它很複雜，這是屬於路易聚集體中的一小部分。
眾所周知，這種蛋白質以疾病的遺傳形式在細胞內環變質。但我們也知道線粒體，也就是細胞的動力室必須要清潔，它們如果被破壞了就必須被清除，如果它們在正常的大腦細胞生長過程和營養過程中受損，那這些線粒體就被破壞了，然後這些被破壞的線粒體就要被重新認知並消除，否則線粒體的破壞會嚴重破壞細胞的正常功能。
因此，控制系統需要始終保持更新，免疫系統在切斷大腦以確保消除傷害方面也有一定作用，但有時也可能會惡化情況，也可能會殺死那些不應該被殺死的細胞，並且有時候降解需要去除的蛋白質會失敗。但無論怎樣，我們已經有了很多碎片信息，現在這是看起來一個簡單的拼圖了。
但事實證明，這個拼圖要複雜的多，有許多的不同的基因和途徑已經在發揮作用了，現在的挑戰是要解決一個可能包含數千個碎片信息的拼圖，然後將它們放在一起創建成圖片，這樣我們就可以看到那些需要通過藥物測試的連結，並且看看我們能否阻止此步驟。
現在我要介紹幾種我們小組準備專注於的方法，因為他們似乎在分子和細胞的攻擊上特別成熟。這其中包括基因，這個過程就是基因在起作用，這些基因在帕金森疾病中以牛頓家族的形式出現，這就是我所說的它對免疫系統起的作用。它可能對增強垂死的大腦區域的損害有關係，我們甚至都不知道那個連接神奇的神經元到其目標的接線圖和電路，這些是即使在普通人腦中也需要被充分理解的。
這是一個漫長的階段，在疾病發展之前就有數十年的時長，有些病人有一些症狀，似乎預示著這種疾病的最終發展，我們還不知道這些症狀的意義，我們不知道如何標記這個疾病的進展，也沒有可以使用的生物標記，我們為了真正的了解這個疾病需要儘早地探索所謂的前驅期。
06
好了，我的幻燈片結束了，但我想再重申一次了解這些過程有多重要。
它在分子和細胞上都對帕金森疾病有害，但我相信我們可以解決它，因為與其它世界上更困難的疾病問題，像心臟病、癌症等，了解了它的分子和細胞並且了解是哪裡出了問題就會讓我們開發出更有效的藥物和手術來控制疾病。儘管心臟病和癌症一直還是致命的疾病，但是因為我們有有效的治療方案讓越來越少的人會因此死亡，對於狹窄的退行性疾病，我們也需要同樣如此，比如帕金森和阿爾茲海默症。
所以我希望你們能對我們對這個問題的熱情有所了解，了解事物的基本工作原理，我希望你們也可以挑戰自己，讓自己也對未來感到興奮。
祝你們好運！
演講原文
English Version
Hello. Welcome to the Kinglead Christmas conference. My name is Randy Scheckman. I'm a professor in the department of molecular and cell biology at the University of California Berkeley.
And I』d like to welcome my friends in China, students of science,aspiring young physicians, and their family members. Because today I'm gonna tell you briefly about why I feel so strongly that basic science of fundamental understanding of processes.
In this case of how cells work can lead us in tremendous directions in understanding the problems that we face,including, for instance, the epidemic that we now suffer and the debilitating diseases, such as nerve degenerative diseases. And I』ll focus on one particular in a moment.
But before I do that, I wanna lead in with a description of my own path to discovery. How that can help you understand the point that I wish to make about the importance of basic science.
So, when I grew up in California,I became interested in microorganisms. And I did this because I had a microscope that I received of that I purchased with earnings that I made with the chores that I did around the neighborhood.This was my Bausch and Lomb student microscope that I used throughout high school to work on independent projects that I entered in local science fairs.
But I put this microscope away when I went off to college. And later as I became a faculty member at the University of California, Berkeley,I continued to study microorganisms because I felt that understanding simple organisms could lend itself to discoveries that were much more difficult to do with more complicated organisms.
And let me make my point by showing you this image.
Which is of yeast cells. These are cells that are used to bake bread and to ferment alcohol,but they are a powerful experimental organism to understand basic life processes.
Because as you'll see, yeast cells use the same mechanisms,the same processes that human cells use to manufacture protein molecules and to package them for export outside of the cell.
This is a process called protein secretion that is very important for all the cells in your body,because they are responsible for organizing the shipment of proteins that go into the blood that go into the lymphatic system, antibody molecules, hormones like insulin.
All these things must be packaged inside of the cell and then exported outside of the cell. And I decided to study this process in baker's yeast,because I believe that it would end up sharing the same machinery as a human cell.
And yet, it has been and still is much simpler to study an organism that you can grow in large quantities in the laboratory,and with which you can do simple genetic manipulations.
This is a cluster v cells that you might find growing on the surface of a grape, and as a yeast cell grows and divides,it begins its life by sending out a small bud. And this bud gets bigger and bigger during the 90 minutes or so that it takes the yeast cell to divide.
Eventually the bud becomes the same size as the mother cell, and then the cells divide in half. And if the nutritional conditions in the growth medium are good,the cell continues to prost do this and can grow exponentially over many generations.
Now if you look inside a yeast cell,you can see some evidence that it's like other cells.
These dots are called ribosome, there the little machines like sewing machines that stitch amino acids together to make proteins.But the cell also has internal membranes, some of which are very much like those that are seen in thin slices through human cells.
We were particularly interested in these small little membranes called vessels,and we showed in genetic and then in biochemical experiments that these vessels can capture proteins that are gonna be secreted outside of the cell to allow it to grow on the surface of a grape.
Now we discovered in the course of our work over many years that the genes that yeast cells use to organize this process are the same genes that we use in the cells in our body to do the same thing, even to manufacture and secrete molecules like insulin.And it became possible to use yeast cells as a platform to organize the production and secretion of clinically important proteins.
So for instance, now, 1/3 of the world's supply of human recombinant insulin that's used to treat diabetic patients is manufactured in giant fermentation vats,as you see here,tens of thousands of leaders growing up to secrete insulin into this growth medium,from which it can be isolated and used for treatment of patients who suffer from diabetes.
It's also been possible to use yeast to manufacture the vaccine that you use when you're immunized against hepatitis b virus,which is a terrible endemic infection within China,90% of the liver cancer that arises in the world is as a result of hepatitis b infection.
And that can now effectively be treated by immunization with particles that are made in yeast.Well, as a result of our discoveries,and perhaps also their application in broader clinical setting.
Now seven years ago, I was awarded the Nobel prize. And here, you see me receiving the diploma in the middle from the king of Sweden in Stockholm.on December now seven years ago.
Now, in addition, just before this award ceremony,I donated to the Nobel museum in Stockholm,that old microscope that began my journey in science.If you ever find yourself in Stockholm,please drop by to see that old microscope together with a description of how it was so important in my development of an interest in science.
Now I'm gonna turn to a different topic, but the same logic.And that is how important basic science can be in understanding even complicated diseases like Parkinson's.
You may know people who suffer from Parkinson's.It's often associated with difficulty moving,sometimes difficulty speaking or coughing.It often is accompanied by a decay in cognitive function, a developing dementia. It is a very serious disease.It can progress for many years.
And it is inevitably fatal.And people die for various reasons when they are flipped with Parkinson's.And yet we don't understand the fundamental basis of this disease.I want to tell you what little we knowand how I'm organizing effort to try to get the molecular and cellular basis of this disease.
First of all, the diseases profound around the world.It's a kind of a pandemic,not unlikely the pandemic that we suffer from now from covid-19.The difference is that the pandemic will certainly be controlled in the next year with a vaccine,whereas Parkinson's continues to march on,it's becoming even more prevalent.Millions of patients suffer from this disease.
And it's estimated that within the next decade or so,almost 20 million people around the world will suffer from the disease,which is largely, but not always a disease of aging. In fact, the disease observes no national boundaries,just like the coronavirus pandemic.
And a particular note to you,almost half now, and in the future,over half of the patients who suffer from Parkinson's disease will be in your country.So, this is something of vital concern to the Chinese government and governments around the world to try to understand this, to develop better treatments.
Now let me tell you a little bit about what's known about what goes wrong.
The disease was first recognized as a movement disorder, now 200 years ago, it's only been in the last 100 years that the disease and understanding is focused on the inability of a region of the brain to manufacture a chemical called dopamine,
which allows nerve cells to communicate with each other,and which, among other things, controls our bodies ability to move and other aspects of emotion and cognition.
Now this region of the brain can be recognized in a section of a brain,in this case, of a person who died for other reasons.And in that section, you can see a dark band that appears small region in the mid brain that is highlighted by the presence of a pigment called melanin,which happens to be produced also by these cells.
And you can see this in the brain of someone who died for other reasons,in the brain of someone who died from Parkinson's disease,this band is largely gone.
That's because by the time of death,almost all those cells have died.Indeed, when someone presents with the symptoms of the disease first some years earlier,almost half of those cells have already died and they continue to die.And nothing can be done yet to control that death.
Now, more recently, a hundred years ago,another British physician by the name of Frederick Lewy looked at history, logical stains of this region of the brain in patients who were suffering from Parkinson's.And he could see that some of these cells had dark bodies that are now called Lewy bodies.
That seemed to be an accumulation of damaged proteins and membranes that stick together and may be the cause of death of these cells,or it may just be a symptom as they are dying, that these things begin to accumulate.
We don't know that. We don't know what brings this about.We don't know what can be done to arrest it. And so many of us have banded together to study these fundamental processes,In the cells of the brain, we can grow in the laboratory.This is a cartoon of nerve cells.Now, how do we study these cells?What can we do to try to understand Parkinson's disease?
Several years ago, I agreed to lead an effort called aligning science across Parkinson's.An effort started in the United States,but which has since become international,where we have brought together teams of investigators from 11 different countries,nearly a hundred different laboratories, teams who agreed to work together on common themes that will allow us to get to the basis of the disease.
We work along with an organization called the Michael J Fox foundation in the United States.But we reach across borders to countries around the world to engage people in a collaborative effort.Because this problem is larger than any one laboratory can solve.
So you might look at the disease as a kind of a puzzle,the puzzle includes pieces.This is a simple depiction of the puzzle with only a small number of pieces.But already just looking at these pieces, you can see that the puzzle is complicated.,this is a protein that is part of those aggregates in Lewy bodies.
And it's known that in a genetic form of the disease, this protein goes bad inside the cell.But we also know that mitochondria, the power houses of the cell, must be cleanse.
They must be removed if they are damaged in the normal course of a cell growing in the brain and being nourished,these mitochondria become damaged,and the damage mitochondria have to be recognized and gotten rid of,or else damage mitochondria can do a great deal of destruction to the normal function of a cell.
So that control system must be renewed all the time. There's also some role for the immune system in severing the brain to make sure that damages gotten rid of.
And sometimes that may go bad,and may actually cause the death of these cells when they shouldn't be killed.And sometimes there's a failure in degrading proteins that need to be removed.Anyway, there are lots of these pieces.Now, this is a simple puzzle.
It turns out that the puzzle is much more complicated,there are many different genes and many different pathways that have been suggested to play a role.And the challenge now is to take a puzzle that may consist of thousands of pieces,and put them together to create a picture that will allow us to see these of links that need to be tested with drugs to see if we can block this step.
Now let me just say there are several approaches that our group has decided to focus on because they seem like they're particularly ripe for attack at a molecular and cellular basis.And that includes the genes.The process is the pathways that these genes play a role in.
These genes have turned up in newton forms in families with Parkinson's disease.There is a role, as I suggested, for the immune system,that may be responsible for or enhance the damage to the regions of the brain that are dying.We don't even know the wiring diagram, the circuitry that connects a dope magic neuron to its targets.These need to be fully understood even in a normal human brain.
And finally, there's a very long phase,sometimes decades long that precedes the development of a disease.
And some patients have some symptoms that seem to predict the eventual development of the disease,we don't know what those symptoms mean,we don't know how to mark the progress of the disease.There are no biological markers that we can use.And we need to explore this early so called prodromal phase, to really understand the disease.
Now I'm gonna stop these slides,and just finish by telling you again how important it is to understand this process.
It goes bad in Parkinson's disease at a molecular and cellular level, and I'm confident that we can do this, because with other diseases that have been even more of a big problem in the world.
Such as heart disease and cancer,understanding the molecules and cells and what goes bad in those diseases has allowed us to develop drugs and surgical procedures that are very effective now in controlling these diseases.
And though heart disease and cancer continue to be a killer,fewer people are dying because we have effective treatments.We need that same thing for narrow degenerative diseases like Parkinson's and Alzheimer's disease.
So I hope you've gotten a flavor for the passion that we bring to these problems,understanding how things work at a fundamental level.And I hope you now can challenge yourself to be excited about that in your future as well.
Good luck to you.