雅美之途
教育，人文，社會
關於新冠病毒溯源，這純粹是個科學的問題，但是現在已經被相當的政治化。我的立場是，應該開放世界各地的血清樣本，武漢病毒所的記錄本，包括購買primers的記錄。如果自己在病毒上問心無槐，邀請業內專家檢查具體實驗記錄是可以理解的步驟。
我一直不排除泄漏，雖然這種可能性很低。這是我長期的認知，如果石正麗發現了新病毒後不報道的可能性極低, 因為她本人是富有競爭力的科學家。但是現在發現武漢所被軍管過，這就為世界尋找真相蒙上了一層疑問。
現在沒有任何痕跡顯示這新冠病毒是經過人工修飾的，新冠病毒為天然病毒。但是病毒學家也告訴我，如果傳代，在動物或細胞中，病毒是會自然突變的，那些突變了的病毒就像是自然的病毒了。但是即使傳代出現突變，要將人工修飾過的地方特異性地突變掉，這種可能性也很低。
現在關於新冠病毒的gain of function（增強功能), 公開發表在Nature的文章是以北卡教授Ralph Baric為主體的，美國要調查先將他查清楚。Baric教授剛當選美國科學院院士，武漢病毒所的科學家隻是輔助，所以要找該項研究的源頭先找這個美國佬，憑什麽美國還選他當院士？
在免疫係統裏，特別是補體中，我們經常見到gain of function, C3或FB都有。造成酶活性增強，然後產生更多的補體片段去造成器官損傷。
中國在外交出的大錯不僅是不怎麽配合，還反咬是美國和意大利的病毒，居然還要求調查美國生物武器係統。甚至將如此的方式上升到國家層麵，不僅僅是小粉紅們，這是令人難以理解的行為。怎麽不能換位思考，想想美國再怎麽也是新冠疫情的受害國。
最公平的態度應該承認現有的資料指向病毒的首發地為中國武漢，但是首發地不見得是真正的原發地。即使原發地也不應該受到譴責，在醫學上病人是不應該受到譴責的。即使是意外泄漏，如果在外交層麵說清楚，也是可以得到世界人民的理解的。現在中國是反攻的太厲害了，如果出現後衛失手就麻煩了。
現在耶魯博士朋友為我提供了這個David Baltimore的訪談錄，我立刻覺得重要，都著手翻譯，估計文學城都可以讀英文而作罷。
David Baltimore是在世的最偉大的病毒學家，也是因為發現RAG酶和NF-kB理應第二次獲得諾貝爾獎的免疫學家，他在早年因為發現逆轉錄酶而與Howard Temin分享諾貝爾獎。巴爾的摩曾經擔任過洛克菲勒大學和加州理工學院的校長。巴爾的摩雖然已經退休，但是腦袋還是很清楚的，他在訪談中提到的太太是華裔Alice Huang。
我在年初聽Baltimore在MIT演講時，他是完全認為病毒是自然的，現在這觀點似乎有所鬆動，但是也不肯定，我們需要更多的證據。
這是他的訪談的關鍵點，我們看他怎麽解釋： "When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus. These features make a powerful challenge to the idea of a natural origin for SARS2."
The Debate over Origins of SARS-CoV-2
June 22, 2021, Caltech
There has been renewed discussion and interest into understanding the biological origins of SARS-CoV-2, the virus that has caused the COVID-19 pandemic. Similar viruses before it have been shown to have jumped from animals to humans; yet this link has not yet been definitively found for SARS-CoV-2.
Caltech's David Baltimore, president emeritus and Distinguished Professor of Biology, is a virologist who received the Nobel Prize for his research into viral genetics. Baltimore was an organizer of the first Asilomar Conference on Recombinant DNA held in 1975 to discuss ethics and regulation of biotechnology. We sat down with him to discuss the debate over the origins of SARS-CoV-2.
What are the arguments that suggest SARS-CoV-2 is a naturally evolved virus? What is the evidence that suggests that it may have originated in and accidentally released from a laboratory in Wuhan, China?
The argument that it's a naturally evolved virus is from the belief that through the time of evolution, any sequence of RNA or DNA could evolve.
Biologists have seen what evolution can create: the whole natural world around us. We believe that evolution can do anything. But the fact that evolution might have been able to generate SARS-CoV-2 doesn't mean that that's how it came about. I think we very much need to find out what was happening in the Wuhan Institute of Virology. I think that we can't say for sure yet whether the SARS-CoV-2 virus came from natural origins or if it was genetically manipulated somehow.
Recently you were quoted as saying: "When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus. These features make a powerful challenge to the idea of a natural origin for SARS2." Can you unpack this quote for us?
Let me be clear, even though I used the phrase "smoking gun," I don't really think there's a smoking gun in the genome itself.
Now, within the SARS-CoV-2 genome there is an insertion of 12 nucleotides that is entirely foreign to the beta-coronavirus class of virus that SARS-CoV-2 is in. There are many other viruses in this class, including the closest relative of SARS-CoV-2 by sequence, and none of them have this sequence. The sequence is called the furin cleavage site.
To back up a little bit: In order to infect a cell, the spike protein on the surface of viruses like SARS-CoV-2 needs to first be cut, or cleaved. The cut needn't be terribly exact, but it needs to be cut. Different viruses attract different kinds of cellular "scissors," so to speak, to make this cut; the furin cleavage site attracts the furin protein providing the most efficient way to make a cut. You don't need a furin cleavage site to cut the protein, but it makes the virus more efficiently infectious.
So where did it come from in SARS-CoV-2? There are other viruses that have furin cleavage sites, other coronaviruses, though not the family of beta-coronaviruses. So this sequence's nucleotides could have hopped from some other virus. No one has identified a virus that has exactly this sequence, but it could have come from something close, then evolved into the sequence that we see today.
I'm perfectly willing to believe that happened, but I don't think it's the only way that that sequence could have appeared. The other way is that somebody could have put it in there. You can't distinguish between the two origins from just looking at the sequence. So, naturally, you want to know were there people in the virology laboratory in Wuhan who were manipulating viral genetic sequences? It's really a question of history: What happened?
When I first saw the sequence of the furin cleavage site—as I've said, other beta coronaviruses don't have that site—it seemed to me a reasonable hypothesis that somebody had put it in there. Now, I don't know if that's true or not, but I do know that it's a hypothesis that must be taken seriously.
Why is it important to know where the virus originated?
Well, I think we want to know the pathway of generating highly infectious new viruses that could cause pandemics because we want to protect ourselves against this happening again. If it happened by natural means, it means that we have to increase our surveillance of the natural environment. We have to try to find the hosts that provide an ability for the virus to change its sequence, to become more infectious. This would mean we need to keep surveillance on markets, on zoos, on places where viruses could jump from one species to another.
But if SARS-CoV-2 came about by an artificial means, it means we've got to put better defenses around laboratories. I'm not suggesting that it was deliberately released if it came from a laboratory, but we have to realize that whatever a laboratory does might get out of the laboratory and create havoc. It means that work of this sort should only go on in what are called biosafety level 4 laboratories.
In the past, you have spoken a lot about the ethics surrounding gene editing technologies like CRISPR/Cas-9. Though the origins of SARS-CoV-2 are still unclear, are there renewed ethical concerns about manipulating viral genomes?
We have a whole toolbox of ways of manipulating the sequences of viral genomes. Those become much more dangerous if they can get out of the lab and cause trouble. That was the genesis of the first Asilomar meeting in 1975. In that meeting, we were discussing ethics around recombinant DNA technology. We were worried that genetically manipulated things could get out of the laboratory and be dangerous. I must say that, at that time, I didn't take the issue of whether, in the process of laboratory experimentation, we might generate dangerous new organisms as seriously as it now appears to me.
But in order to try to understand crossover events and prepare for the next pandemic, scientists need to be able to study viruses in the lab. How do we balance safety with the potential good that can come from studying viruses?
We want to know what tricks viruses have evolved, because those are useful to us in a lot of ways: They tell us what to keep an eye on, what to watch out for. Viruses are very inventive in that sense. They have all sorts of tricks, many of which we haven't seen in organisms other than viruses. We want to know about all of these so that we can be prepared to counter them.
Work in virology is very important from that point of view and also actually gives us tricks that we can use in designing, for instance, gene therapy vectors that are carriers of beneficial genes or therapeutic molecules. At Caltech, my colleagues are developing these types of viral vector technologies that could treat, for example, Huntington's disease.
When I looked at the world of viruses 20, 30 years ago, I was a younger virologist. It seemed to me that there was very little that viruses did that was good. Most of what they did was bad, caused disease of various sorts, even cancer. Today, there is the ability to manipulate viruses. Researchers can remove the genetic material that makes a virus dangerous, that makes people ill, and instead use the virus as a package to get a desired therapeutic into cells. That's an incredibly powerful, positive thing that viruses can do. They don't naturally treat diseases, but we can manipulate them so that they become vectors that allow us to fight diseases.
For more Caltech experts on COVID-19, visit the Caltech Science Exchange.
原文地址：
https://www.caltech.edu/about/news/the-debate-over-origins-of-sars-cov-2
你的麻煩不是你自己信服什麽，而是想要別人也信服你那一套。
未必“大家都想查”，中國除了讓外咬部的戰狼甩鍋，有像美國這樣查了首例確診前的西雅圖流感樣本和首例確診前38天的血樣中的抗體嗎？
如果中國的衛生防疫部門也查了，請提供鏈接。
你既然自稱“隻一個吃瓜群眾”，那就沒必要如此喋喋不休地推銷那幾個僅在文學城博客匿名發表而不在專業出版物上具名發表的“非人工來源”之說吧。
現在大家都想查，我隻一個吃瓜群眾根本沒查的權利和義務。我隻是猜測人也可以是中間宿主，病毒在人際間不停變異，到了2019就可以大量讓人致死了。我們的思維不能隻停留在必須動物是中間宿主上。也不能單純模擬2003薩斯模式和中東薩斯傳染模式。
這病毒沒準就是感冒病毒變異的呢，當然這必須由真懂病毒進化的人判斷。可能我說的根本不對。我隻是目前更相信非人工來源。
現在大家都想查，我隻一個吃瓜群眾根本沒查的權利和義務。我隻是猜測人也可以是中間宿主，病毒在人際間不停變異，到了2019就可以大量讓人致死了。我們的思維不能隻停留在必須動物是中間宿主上。也不能單純模擬2003薩斯模式和中東薩斯傳染模式。
這病毒沒準就是感冒病毒變異的呢，當然這必須由真懂病毒進化的人判斷。可能我說的根本不對。我隻是目前更相信非人工來源。
外交部官網公布的趙立堅6月23日記者會記錄中是這麽寫的：“如果這位議員想探尋結論，建議他不妨從威斯康星州驅車前往德特裏克堡，了解一下那裏的真相或許有所幫助”。這應該是改過的，卻沒有改好，威州距離德堡太遠了，一般不會驅車前往。趙也許有口誤，其本意可能是要說”驅車到離華盛頓國會僅一小時車程的德特裏克堡“。
大家認同這些變異的進化關係，不是靠推測，而是靠實驗查證比對來自巴西、南非、英國、印度的樣本。
你要大家認同“人就是中間宿主”，你就要拿出“在人群內不停變異”的樣本來證明，否則就是那種“各說各的”。
你不查，樣本從哪裏來？
很可能新冠病毒在2019年前一直和感冒病毒類似在人際間傳播，在人群內不停變異，最後成了現在薩斯二號呢。人也是動物，人也可以是中間宿主。
大家認知水平不一樣，有時候很難知道對方認知在哪種水平上。所以不同層次人群吵來吵去的。都各說各的。
林子大了，什麽鳥都有。
即使推測人就是中間宿主，也隻能靠溯源查證。
你不是也說“新冠在人體上不停變異”嗎？你憑什麽這樣說，不也是查出來的嗎？
你再去看看下麵凡人博主的鏈接論文。
我今天感覺傾向於遍野無塵博主大膽的推測：人就是中間宿主。
從一年以來新冠在人體上不停變異，我們應該可以猜出些來了。
的確，薩斯的源頭是過了很多年才找到。
但那次找到中間宿主很快，半年不到。
2002年12月15日中國確診首例非典肺炎病人廚師黃杏初，2003年5月22日香港大學管軼把確認果子狸為中間宿主的論文提交給《科學》雜誌。
'A spokesperson for the Ministry of Foreign Affairs of the People's Republic of China, Zhao Lijian, said that US labs should instead be investigated, and that some people in the United States “don't care about facts or truth and have zero interest in a serious science-based study of origins”.'
我的意思說這篇論文幾乎囊括了科學界和政治界以及網絡上的各種討論到的話題。沒想到這篇文章連趙立堅的發言都些進來了。
2003到2005的薩斯是過了很多年才找到源頭的。我想沒準碰巧哪天這個病毒起源也能被解密。
很好奇你提到的“趙立堅的質疑”是什麽。
網上搜了一下，他6月23日稱“如果這位議員想探尋結論，建議他不妨驅車到離威斯康星州僅一小時車程的德特裏克堡，了解一下那裏的真相或許有所幫助”。
作為一個國家的發言人，不可張口胡說。
從威斯康星到德特裏克堡，坐飛機都要二小時，開車怎麽可能“僅一小時”？
如此兒戲，有何信譽可言！
關於刺突基因片段和人工證據解釋的很好。這些對於普通人很難理解，我還是勉強看明白了。
Andersen says that Baltimore was incorrect about that detail, however. In SARS-CoV-2, about 3% of the nucleotides encoding arginine are CGG, he says. And he points out that around 5% of those encoding arginine in the virus that caused the original SARS epidemic are CGG, too. In an e-mail to Nature, Baltimore says Andersen could be correct that evolution produced SARS-CoV-2, but adds that “there are other possibilities and they need careful consideration, which is all I meant to be saying”
https://www.nature.com/articles/d41586-021-01529-3
回複 'curiousGeorge2' 的評論 :
很多人喊那個弗林蛋白酶切點是新冠獨特的，這些人包括那個叫最近很活躍的MIT的博後Alina Chan。隻是這些人都是跟著喊，卻沒做homework。
其實那個所謂的arginine（精氨酸，縮寫R）並不是什麽smoking gun，也不是新冠特有的。
很多人這麽說是因為他們隻和沒有這個R的薩斯病毒比較，而沒有和其它有這個R的冠狀病毒比較。很久以前就有文提到了這一點，不畫了一個很直觀的圖，我在下麵這個鏈接裏的一文裏引用了改圖並詳細的講解過。
https://blog.wenxuecity.com/myblog/73963/202002/29594.html
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Thank you. But any of these facts will not matter for those people who already are much invested in the lab-leak theory.
上麵的話表明：這個福林蛋白裂解位點是SARSCOVID2冠狀病毒獨有的。
上麵的話表明：這個福林蛋白裂解位點是這類冠狀病毒獨有的。
下麵有人說其它冠狀病毒也有這類福林蛋白裂解位點，隻是沒人去比較有這種裂點的冠狀病毒。
人類目前為止不是隻發現六種冠狀病毒嗎？其它冠狀病毒有沒有不是很清楚就知道嗎？
很多人喊那個弗林蛋白酶切點是新冠獨特的，這些人包括那個叫最近很活躍的MIT的博後Alina Chan。隻是這些人都是跟著喊，卻沒做homework。
其實那個所謂的arginine（精氨酸，縮寫R）並不是什麽smoking gun，也不是新冠特有的。
很多人這麽說是因為他們隻和沒有這個R的薩斯病毒比較，而沒有和其它有這個R的冠狀病毒比較。很久以前就有文提到了這一點，不畫了一個很直觀的圖，我在下麵這個鏈接裏的一文裏引用了改圖並詳細的講解過。
https://blog.wenxuecity.com/myblog/73963/202002/29594.html
also in human DNA.
這件事，有點正常腦筋，都明白最大的可能性是什麽。軍管，讓人非常容易聯想到病毒武器，毀滅證據拒絕檢查，更是可疑，中國目前經濟是第二，經濟的質量，前十都沒有，在世界上的信譽前50也沒有，產品除了便宜，別的啥也不是
沒找到，這不得不讓人懷疑可能是泄露。