诺贝尔奖得主David Baltimore谈新冠病毒的起源

关于新冠病毒溯源，这纯粹是个科学的问题，但是现在已经被相当的政治化。我的立场是，应该开放世界各地的血清样本，武汉病毒所的记录本，包括购买primers的记录。如果自己在病毒上问心无槐，邀请业内专家检查具体实验记录是可以理解的步骤。

我一直不排除泄漏，虽然这种可能性很低。这是我长期的认知，如果石正丽发现了新病毒后不报道的可能性极低, 因为她本人是富有竞争力的科学家。但是现在发现武汉所被军管过，这就为世界寻找真相蒙上了一层疑问。

现在没有任何痕迹显示这新冠病毒是经过人工修饰的，新冠病毒为天然病毒。但是病毒学家也告诉我，如果传代，在动物或细胞中，病毒是会自然突变的，那些突变了的病毒就像是自然的病毒了。但是即使传代出现突变，要将人工修饰过的地方特异性地突变掉，这种可能性也很低。

现在关于新冠病毒的gain of function（增强功能), 公开发表在Nature的文章是以北卡教授Ralph Baric为主体的，美国要调查先将他查清楚。Baric教授刚当选美国科学院院士，武汉病毒所的科学家只是辅助，所以要找该项研究的源头先找这个美国佬，凭什么美国还选他当院士？

在免疫系统里，特别是补体中，我们经常见到gain of function, C3或FB都有。造成酶活性增强，然后产生更多的补体片段去造成器官损伤。

中国在外交出的大错不仅是不怎么配合，还反咬是美国和意大利的病毒，居然还要求调查美国生物武器系统。甚至将如此的方式上升到国家层面，不仅仅是小粉红们，这是令人难以理解的行为。怎么不能换位思考，想想美国再怎么也是新冠疫情的受害国。

最公平的态度应该承认现有的资料指向病毒的首发地为中国武汉，但是首发地不见得是真正的原发地。即使原发地也不应该受到谴责，在医学上病人是不应该受到谴责的。即使是意外泄漏，如果在外交层面说清楚，也是可以得到世界人民的理解的。现在中国是反攻的太厉害了，如果出现后卫失手就麻烦了。

现在耶鲁博士朋友为我提供了这个David Baltimore的访谈录，我立刻觉得重要，都着手翻译，估计文学城都可以读英文而作罢。

David Baltimore是在世的最伟大的病毒学家，也是因为发现RAG酶和NF-kB理应第二次获得诺贝尔奖的免疫学家，他在早年因为发现逆转录酶而与Howard Temin分享诺贝尔奖。巴尔的摩曾经担任过洛克菲勒大学和加州理工学院的校长。巴尔的摩虽然已经退休，但是脑袋还是很清楚的，他在访谈中提到的太太是华裔Alice Huang。

我在年初听Baltimore在MIT演讲时，他是完全认为病毒是自然的，现在这观点似乎有所松动，但是也不肯定，我们需要更多的证据。

这是他的访谈的关键点，我们看他怎么解释： "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

[xilaideng]

回复 'cowwoman' 的评论 :
你的麻烦不是你自己信服什么，而是想要别人也信服你那一套。

[cowwoman]

回复 'xilaideng' 的评论 : 没有推销他们。他们说的目前更让我信服。

[xilaideng]

回复 'cowwoman' 的评论 :
未必“大家都想查”，中国除了让外咬部的战狼甩锅，有像美国这样查了首例确诊前的西雅图流感样本和首例确诊前38天的血样中的抗体吗？
如果中国的卫生防疫部门也查了，请提供链接。
你既然自称“只一个吃瓜群众”，那就没必要如此喋喋不休地推销那几个仅在文学城博客匿名发表而不在专业出版物上具名发表的“非人工来源”之说吧。

[cowwoman]

回复xilaideng，

现在大家都想查，我只一个吃瓜群众根本没查的权利和义务。我只是猜测人也可以是中间宿主，病毒在人际间不停变异，到了2019就可以大量让人致死了。我们的思维不能只停留在必须动物是中间宿主上。也不能单纯模拟2003萨斯模式和中东萨斯传染模式。
这病毒没准就是感冒病毒变异的呢，当然这必须由真懂病毒进化的人判断。可能我说的根本不对。我只是目前更相信非人工来源。

[cowwoman]

回复xilaideng，

现在大家都想查，我只一个吃瓜群众根本没查的权利和义务。我只是猜测人也可以是中间宿主，病毒在人际间不停变异，到了2019就可以大量让人致死了。我们的思维不能只停留在必须动物是中间宿主上。也不能单纯模拟2003萨斯模式和中东萨斯传染模式。
这病毒没准就是感冒病毒变异的呢，当然这必须由真懂病毒进化的人判断。可能我说的根本不对。我只是目前更相信非人工来源。

[short_circuit]

回复 'xilaideng' 的评论 :
外交部官网公布的赵立坚6月23日记者会记录中是这么写的：“如果这位议员想探寻结论，建议他不妨从威斯康星州驱车前往德特里克堡，了解一下那里的真相或许有所帮助”。这应该是改过的，却没有改好，威州距离德堡太远了，一般不会驱车前往。赵也许有口误，其本意可能是要说”驱车到离华盛顿国会仅一小时车程的德特里克堡“。

[fonsony]

川大嘴一语定音、病毒是中国制造的、虽然下边的卒仔不会十分认同、但脑装已打上烙印了、更情报机构与肥猪彭嫖确认是武汉病毒研究所放出、去年、美政府的人员说病毒问题、全是中国克于制造、那赵立坚才在自家网上说美国军人带来、我当时的想法是赵个人发海气之言、但对比美方对中国的攻击当时比例是牛比与蚊比、

[xilaideng]

回复 'cowwoman' 的评论 :
大家认同这些变异的进化关系，不是靠推测，而是靠实验查证比对来自巴西、南非、英国、印度的样本。
你要大家认同“人就是中间宿主”，你就要拿出“在人群内不停变异”的样本来证明，否则就是那种“各说各的”。
你不查，样本从哪里来？

[cowwoman]

我指的新冠在人体不停变异是基于这一年多来，萨斯二号病毒发生了南非变异，伦敦变异，印度变异，巴西变异的实际情况。
很可能新冠病毒在2019年前一直和感冒病毒类似在人际间传播，在人群内不停变异，最后成了现在萨斯二号呢。人也是动物，人也可以是中间宿主。
大家认知水平不一样，有时候很难知道对方认知在哪种水平上。所以不同层次人群吵来吵去的。都各说各的。

[xilaideng]

回复 'cowwoman' 的评论 :
林子大了，什么鸟都有。
即使推测人就是中间宿主，也只能靠溯源查证。
你不是也说“新冠在人体上不停变异”吗？你凭什么这样说，不也是查出来的吗？

[cowwoman]

你去看看遍野无尘博主的几篇新冠文章，写的也相当好。他推测人就是中间宿主。
你再去看看下面凡人博主的链接论文。

我今天感觉倾向于遍野无尘博主大胆的推测：人就是中间宿主。

从一年以来新冠在人体上不停变异，我们应该可以猜出些来了。

[xilaideng]

回复 'cowwoman' 的评论 :
的确，萨斯的源头是过了很多年才找到。
但那次找到中间宿主很快，半年不到。
2002年12月15日中国确诊首例非典肺炎病人厨师黄杏初，2003年5月22日香港大学管轶把确认果子狸为中间宿主的论文提交给《科学》杂志。

[cowwoman]

这是自然文章的原文：
'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”.'

我的意思说这篇论文几乎囊括了科学界和政治界以及网络上的各种讨论到的话题。没想到这篇文章连赵立坚的发言都些进来了。
2003到2005的萨斯是过了很多年才找到源头的。我想没准碰巧哪天这个病毒起源也能被解密。

[xilaideng]

回复 'cowwoman' 的评论 :
很好奇你提到的“赵立坚的质疑”是什么。
网上搜了一下，他6月23日称“如果这位议员想探寻结论，建议他不妨驱车到离威斯康星州仅一小时车程的德特里克堡，了解一下那里的真相或许有所帮助”。
作为一个国家的发言人，不可张口胡说。
从威斯康星到德特里克堡，坐飞机都要二小时，开车怎么可能“仅一小时”？
如此儿戏，有何信誉可言！

[cowwoman]

自然这篇论文写的真棒，把普通大众的各种疑惑全面解释了一遍，连赵立坚的质疑都写上了，很有说服力。
关于刺突基因片段和人工证据解释的很好。这些对于普通人很难理解，我还是勉强看明白了。

[curiousGeorge2]

A Medium article that speculates on a lab origin for SARS-CoV-2 quotes David Baltimore, a Nobel laureate and professor emeritus at the California Institute of Technology in Pasadena, as saying that viruses don’t usually have that particular code for arginine, but humans often do — a “smoking gun”, hinting that researchers might have tampered with SARS-CoV-2’s genome.

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

[cowwoman]

武毒所的人可能肯本没本事干这事儿。西方人可能高看武汉科学家了。

[curiousGeorge2]

Fanreninus 发表评论于 2021-07-04 07:00:51
回复 'curiousGeorge2' 的评论 :

很多人喊那个弗林蛋白酶切点是新冠独特的，这些人包括那个叫最近很活跃的MIT的博后Alina Chan。只是这些人都是跟着喊，却没做homework。
其实那个所谓的arginine（精氨酸，缩写R）并不是什么smoking gun，也不是新冠特有的。
很多人这么说是因为他们只和没有这个R的萨斯病毒比较，而没有和其它有这个R的冠状病毒比较。很久以前就有文提到了这一点，不画了一个很直观的图，我在下面这个链接里的一文里引用了改图并详细的讲解过。
https://blog.wenxuecity.com/myblog/73963/202002/29594.html

-----

Thank you. But any of these facts will not matter for those people who already are much invested in the lab-leak theory.

[irisin2021]

不管武汉是病毒的源发地，还是案发地，都应该从武汉查起。为什么不愿意查呢？

[irisin2021]

若是病毒泄露，对全世界是最大喜讯。因为人们完全有能力防止这种事再次发生。如果不是，又查不出中间传播途径，covid-XX就可能再次来临。最可怕的是，全世界科学家翻箱倒柜查找传播中间体，花费巨大人力和财力，最后武汉病毒所说，他们病毒菌株库中有covid19.

[cowwoman]

已知可感染人类的冠状病毒共有7种，其中有4種（人類冠狀病毒229E、人類冠狀病毒OC43、人類冠狀病毒NL63與人類冠狀病毒HKU1）可引发普通感冒，另外3種為導致嚴重疾病的严重急性呼吸道综合征冠状病毒（SARS-CoV）、中東呼吸症候群冠狀病毒（MERS-CoV）與严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2），皆曾在全球各地造成疫情。此外還有許多冠狀病毒可感染家畜與家禽、寵物、實驗動物和野生動物，例如感染雞隻的禽冠狀病毒、感染豬隻的數種豬冠狀病毒、感染犬與貓的犬冠狀病毒和貓冠狀病毒、感染實驗小鼠與大鼠的鼠冠狀病毒。

[cowwoman]

重新说一下。
上面的话表明：这个福林蛋白裂解位点是SARSCOVID2冠状病毒独有的。

[cowwoman]

'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.'

上面的话表明：这个福林蛋白裂解位点是这类冠状病毒独有的。

下面有人说其它冠状病毒也有这类福林蛋白裂解位点，只是没人去比较有这种裂点的冠状病毒。

人类目前为止不是只发现六种冠状病毒吗？其它冠状病毒有没有不是很清楚就知道吗？

[voiceofme]

医学上我不知道。 但新冠是从中国起的，现在变成了影响整个人类的大事。这么大的影响整个人类的事情，中国应该采取积极的态度去调查和配合调查。可以这样说，这个事情比一百年前八国联军还要大。中国的抵赖或者COVER-UP只会让别人更加怀疑。

[Fanreninus]

下面的“不画了一个很直观的图”应为“还画了一个很直观的图”，抱歉！

[Fanreninus]

回复 'curiousGeorge2' 的评论 :

很多人喊那个弗林蛋白酶切点是新冠独特的，这些人包括那个叫最近很活跃的MIT的博后Alina Chan。只是这些人都是跟着喊，却没做homework。
其实那个所谓的arginine（精氨酸，缩写R）并不是什么smoking gun，也不是新冠特有的。
很多人这么说是因为他们只和没有这个R的萨斯病毒比较，而没有和其它有这个R的冠状病毒比较。很久以前就有文提到了这一点，不画了一个很直观的图，我在下面这个链接里的一文里引用了改图并详细的讲解过。
https://blog.wenxuecity.com/myblog/73963/202002/29594.html

[curiousGeorge2]

This sequence appears in other coronavirus, and
also in human DNA.

[helix22]

博主怎么看巴尔的摩说的sequence可以是人工做的？他没有说怎么不留痕迹。 另外，最后一个问题他是答非所问，记者问怎样平衡做实验了解病毒与可能带来的危险性，他却整个地讲一个具体的研究病毒带来的好处(viral vector).

[天涯无芳草]

Lost man 评论很精辟。事出反常必有妖。看看中共的一系列神操作，就知道肯定不干净

[许家湾]

如果都有谍报系统资料显示就是美国军方的p4泄漏呢？那是不是可以解释中方的态度？

[Rosaline]

Common sense, 那个华南海鲜市场在武汉闹市，旁边是协和医院的附属肿瘤医院，武汉最好的肿瘤医院，协和医院老教授的新公寓大院，新修的欧式娱乐美食中心，会有蝙蝠引起的传染病？武汉人有几个见过蝙蝠？要岀问题，也是云南等山里的事…，

[smithmaella]

你再说找真相、谈人权、讲诚信，让血肉做的钢铁长城让你头破血流。

[lostman]

外国的科学家不了解中国的现实，他以为中国的科技人员也西方国家一样拥有学术自由，可以自主自己的研究，同样，中国的外交也是不了解西方，按着自己的5000年垃圾文化使诈使计，虚张声势，结果反而给人留下口实。
这件事，有点正常脑筋，都明白最大的可能性是什么。军管，让人非常容易联想到病毒武器，毁灭证据拒绝检查，更是可疑，中国目前经济是第二，经济的质量，前十都没有，在世界上的信誉前50也没有，产品除了便宜，别的啥也不是

[24桥]

主要是中间宿主到现在还
没找到，这不得不让人怀疑可能是泄露。