人类与病毒之战将会走向何方
What the Future May Hold for the Coronavirus and Us
EMILY ANTHES
2021年10月14日
On Jan. 9, 2020, about a week after the world first learned of a mysterious cluster of pneumonia cases in central China, authorities announced that scientists had found the culprit: a novel coronavirus.
2020年1月9日，在世界首次得知中国中部出现一批神秘的肺炎病例大约一周后，当局宣布科学家找到了罪魁祸首：一种新型冠状病毒。
It was a sobering announcement, and an unnervingly familiar one. Nearly two decades earlier, a different coronavirus had hurdled over the species barrier and sped around the world, causing a lethal new disease called severe acute respiratory syndrome, or SARS. The virus, which became known as SARS-CoV, killed 774 people before health officials contained it.
这是个令人警醒的声明，而可怕的是，这个情景并不陌生。大约20年前，另一种冠状病毒跨越了物种屏障，在世界各地快速传播，引发了一种致命的新疾病——严重急性呼吸系统综合征，即SARS。这种病毒被称为SARS-CoV，在卫生官员将其控制住之前，它导致了全球774人死亡。
But even as scientists worried that history might be repeating itself, there was one glimmer of hope. Although all viruses evolve, coronaviruses are known to be relatively stable, changing more slowly than the common flu.
不过，尽管科学家们担心历史可能会重演，但还是有一线希望。虽然所有的病毒都会进化，但根据目前的了解，冠状病毒相对稳定，变化比普通流感慢。
“There was, I think, a sense that would work in our favor, and that the nightmare scenario of it being like influenza — constantly changing and needing updated vaccines all the time — would probably not be the case,” said Dr. Adam Lauring, a virologist and infectious disease physician at the University of Michigan.
密歇根大学(University Of Michigan)病毒学家、传染病医生亚当·劳雷(Adam Lauring)博士说，“我认为，当时有一种对我们有利的感觉，那就是它不会变成流感一样的噩梦——不断变化，一直需要更新疫苗。”
What many scientists had not counted on was unchecked global spread. Over the following weeks, the new virus, SARS-CoV-2, skipped from Wuhan, China, to a cruise ship in Japan, a small town in northern Italy and a biotechnology conference in Boston. Country by country, global coronavirus trackers turned red.
许多科学家没有料到的是，这种病毒会在全球肆意蔓延。在接下来的几周里，新病毒SARS-CoV-2从中国武汉传到了日本的一艘邮轮、意大利北部的一个小镇，以及在波士顿举行的一场生物科技会议。一个国家接一个国家，全球都变成了红色。
To date, more than 237 million people have been infected with the virus, and 4.8 million have died — 700,000 in the United States alone.
到目前为止，全球已有超过2.37亿人感染了这种病毒，480万人死亡，仅美国就有70万人死亡。
Even for a virus, evolution is a long game, and our relationship with SARS-CoV-2 is still in its infancy. We are extremely unlikely to eradicate the virus, scientists say, and what the next few years — and decades — hold is difficult to predict.
即使对于病毒来说，进化也是一个漫长的过程，我们与SARS-CoV-2的关系仍处于开始阶段。科学家们说，我们很有可能无法彻底消灭这种病毒，而且很难预测未来几年乃至几十年的发展。
But the legacy of past epidemics, as well as some basic biological principles, provides clues to where we could be headed.
但是，过去的疫情所留下的遗产，以及一些基本的生物学原理，为我们可能走向何方提供了线索。
The genetic lottery
基因彩票
Viruses are replication machines, hijacking our cells to make copies of their own genomes. Sometimes they make small mistakes, akin to typos, as they replicate.
病毒是复制机，劫持我们的细胞来复制自己的基因组。有时它们在复制过程中会犯一些小错误，这类似于错别字。
Most of the time, these errors have no benefit for the virus; many are harmful and quickly disappear. But occasionally, a virus hits the genetic lottery: a mutation that confers an advantage. This fitter version of the virus can then outcompete its peers, giving rise to a new variant.
大多数时候，这些错误对病毒没有好处；许多错误是有害的，不过很快就会消失。但偶尔，病毒会中基因彩票：一种带来优势的突变。这种更合适的病毒版本在竞争中胜出，从而导致新的变种产生。
The coronavirus could shift in countless ways, but there are three concerning possibilities: It could become more transmissible, it could become better at evading our immune system or it could become more virulent, causing more serious disease.
冠状病毒可能会以无数种方式变化，但有三种可能性令人担忧：可能会变得更具传播性、可能会更善于绕过我们的免疫系统、可能会变得更具毒性，导致更严重的疾病。
SARS-CoV-2 has already become more transmissible. “The virus is just better at transmitting from one person to another than it was in January of 2020,” said Jesse Bloom, an expert in viral evolution at the Fred Hutchinson Cancer Research Center in Seattle. “And this is due to a variety of mutations that the virus has acquired, some of which we understand and some of which we don’t.”
SARS-CoV-2已经变得更具传染性。“与2020年1月相比，这种病毒在人际传播的能力增强了，”西雅图弗雷德·哈钦森癌症研究中心(Fred Hutchinson Cancer Research Center)的病毒进化专家杰西·布鲁姆(Jesse Bloom)说。“这是由于病毒获得了各种突变，其中的一些我们了解，另一些我们不了解。”
One of the first of these mutations had already emerged by late January 2020. The mutation, D614G, likely stabilized the spike protein that the virus uses to latch onto human cells, making the virus more infectious. It quickly became widespread, displacing the original version of the virus.
到2020年1月底，首批突变之一已经出现。这种名为D614G的突变可能稳定了病毒用来粘附在人类细胞上的刺突蛋白，使病毒更具传染性。它迅速蔓延开来，取代了最初的病毒版本。
As the virus spread, more mutations sprang up, giving rise to even more transmissible variants. First came Alpha, which was about 50 percent more infectious than the original virus, and soon Delta, which was, in turn, roughly 50 percent more infectious than Alpha.
随着病毒的传播，更多变异出现了，产生了更具传染性的变异。首先是阿尔法(Alpha)变异毒株，其传染性比最初的病毒高50%，然后是德尔塔(Delta)变异毒株，其传染性又比阿尔法病毒高大约50%。
“It’s hard to imagine that the virus is going to pop into a new species perfectly formed for that species,” said Andrew Read, an evolutionary microbiologist at Penn State University. “It’s bound to do some adaptation.”
“很难想像病毒会突然形成一个完美的新种类，”宾夕法尼亚州立大学(Penn State University)的进化微生物学家安德鲁·里德(Andrew Read)说。“它一定会做一些调整。”
But scientists don’t expect this process to continue forever.
但科学家并不认为这一过程会永远持续下去。
There are likely to be some basic biological limits on just how infectious a particular virus can become, based on its intrinsic properties. Viruses that are well adapted to humans, such as measles and the seasonal influenza, are not constantly becoming more infectious, Dr. Bloom noted.
基于特定病毒的内在特性，其传染性可能存在一些基本的生物限制。布卢姆博士指出，像麻疹和季节性流感这样对人类适应性很强的病毒不会不断变得更具传染性。
It is not entirely clear what the constraints on transmissibility are, he added, but at the very least, the new coronavirus cannot replicate infinitely fast or travel infinitely far.
他补充说，目前还不完全清楚限制传播的因素是什么，但至少，新冠病毒不能无限地快速复制，也不能无限地长途传播。
“Transmission requires one person to somehow exhale or cough or breathe out the virus, and it to land in someone else’s airway and infect them,” Dr. Bloom said. “There are just limits to that process. It’s never going to be the case that I’m sitting here in my office, and I’m giving it to someone on the other side of Seattle, right?”
“传播需要一个人以某种方式通过呼气或咳嗽传出该病毒，然后病毒进入其他人的呼吸道，感染他们，”布鲁姆说。“这个过程是有限制的。我坐在办公室里，就把它传给西雅图另一头的人，这种事永远不会发生，对吧？”
He added: “Whether the Delta variant is already at that plateau, or whether there’s going to be further increases before it gets to that plateau, I can’t say. But I do think that plateau exists.”
他还说：“我不能说德尔塔变异是否已经达到了稳定期，或者在达到稳定期之前是否还会有进一步的发展。但我确实认为这种稳定期是存在的。”
Dodging immunity
躲避免疫
In addition to becoming more transmissible, some variants have also acquired the ability to dodge some of our antibodies. Antibodies, which can prevent the virus from entering our cells, are engineered to latch onto specific molecules on the surface of the virus, snapping into place like puzzle pieces. But genetic mutations in the virus can change the shape of those binding sites.
除了变得更具传染性之外，一些变体还获得了躲避我们某些抗体的能力。抗体可以阻止病毒进入我们的细胞，它被设计成粘附在病毒表面的特定分子，像拼图碎片一样扣在上面。但病毒中的基因突变可以改变这些结合点的形状。
“If you change that shape, you can make it impossible for an antibody to do its job,” said Marion Pepper, an immunologist at the University of Washington School of Medicine.
“如果你改变了这种形状，抗体就无法发挥作用，”华盛顿大学医学院(University of Washington School of Medicine)的免疫学家马里恩·佩珀(Marion Pepper)说。
Delta appears to evade some antibodies, but there are other variants, particularly Beta, that are even better at dodging these defenses. For now, Delta is so infectious that it has managed to outcompete, and thus limit the spread of, these stealthier variants.
德尔塔变异似乎能避开一些抗体，但还有其他变异能更好地避开这些防御，尤其是贝塔(Beta)变异毒株。目前，德尔塔变异的传染性很强，成功地超越了那些隐蔽的变异，从而限制了它们的传播。
But as more people acquire antibodies against the virus, mutations that allow the virus to slip past these antibodies will become even more advantageous. “The landscape of selection has changed,” said Jessica Metcalf, an evolutionary biologist at Princeton University. “From the point of view of the virus, it’s no longer, ‘I just bop around, and there’s a free host.’”
但随着越来越多的人获得针对该病毒的抗体，使该病毒能够避开这些抗体的突变将变得更加有利。“选择的格局已经改变，”普林斯顿大学(Princeton University)进化生物学家杰西卡·梅特卡夫(Jessica Metcalf)说。 “从病毒的角度来看，它不再是‘我四处游荡，就能得到一个免费宿主。’”
The good news is that there are many different kinds of antibodies, and a variant with a few new mutations is unlikely to escape them all, experts said.
专家说，好消息是，有许多不同种类的抗体，一个带有一些新突变的变体不太可能逃脱所有的抗体。
“The immune system has also evolved to have plenty of tricks up its sleeve to counteract the evolution of the virus,” Dr. Pepper said. “Knowing that there is this complex level of diversity in the immune system allows me to sleep better at night.”
“免疫系统也已经进化到有很多办法来对抗病毒的进化，”佩珀说。“知道免疫系统中存在这种复杂的多样性水平，让我觉得安心。”
Certain T cells, for instance, destroy virus-infected cells, helping to reduce the severity of disease. Together, our assortment of T cells can recognize at least 30 to 40 different pieces of SARS-CoV-2, researchers have found.
例如，某些T细胞可以摧毁被病毒感染的细胞，帮助减轻疾病的严重程度。研究人员发现，我们的T细胞组合在一起，至少可以识别30到40个不同的SARS-CoV-2片段。
“It’s a lot harder to evade T cell responses than antibody responses,” said Dr. Celine Gounder an infectious disease specialist at the New York University Grossman School of Medicine.
“避开T细胞反应比避开抗体反应要困难得多，”纽约大学格罗斯曼医学院(New York University Grossman School of Medicine)传染病专家席琳·冈德(Celine Gounder)博士说。
“They’re actually a library of guesses that the immune system makes about what variants might look like in the future,” said Shane Crotty, a virologist at the La Jolla Institute for Immunology.
“它们实际上是免疫系统对未来变异的猜测库，”拉霍亚免疫研究所(La Jolla Institute for Immunology)的病毒学家谢恩·克罗蒂(Shane Crotty)说。
So far, studies suggest that our antibody, T cell and B cell responses are all working as expected when it comes to SARS-CoV-2. “This virus is mostly playing by immunological rules we understand,” Dr. Crotty said.
到目前为止，研究表明，对于SARS-CoV-2，我们的抗体、T细胞和B细胞反应都在按预期工作。“这种病毒在很大程度上是按照我们所了解的免疫规则运行的，”克罗蒂博士说。
‘No interest in killing us’
“对杀死我们没有兴趣”
Whether the virus will become more virulent — that is, whether it will cause more serious disease — is the hardest to predict, scientists said. Unlike transmissibility or immune evasion, virulence has no inherent evolutionary advantage.
科学家说，病毒是否会变得更具毒性——也就是说，它是否会导致更严重的疾病——是最难预测的。与传播性或免疫逃避不同，毒性没有内在的进化优势。
“The virus has no interest in killing us,” Dr. Metcalf said. “Virulence only matters for the virus if it works for transmission.”
“病毒对杀死我们没有兴趣，”梅特卡夫说。“毒性只有在对传播有用时，才对病毒重要。”
Because people who are hospitalized may be less likely to spread the virus than those who are walking around with the sniffles, some have theorized that new viruses become milder over time.
比起那些流着鼻涕四处走动的人，住院的人更不可能传播病毒，因此一些人认为，随着时间的推移，新的病毒会变得更温和。
It is too early to say whether SARS-CoV-2 will change in virulence over the long-term. There could certainly be trade-offs between virulence and transmission; variants that make people too sick too quickly may not spread very far.
SARS-CoV-2的毒性是否会在长期内发生变化，现在还不能下结论。在毒性和传播之间肯定会有权衡；让人病得太严重、太快的变异，可能不会传播很远。
Then again, this virus spreads before people become severely ill. As long as that remains true, the virus could become more virulent without sacrificing transmissibility.
而且，这种病毒在人们病情变得严重之前就已经在传播了。只要这一点保持不变，病毒就可以在不牺牲传播性的情况下变得更具毒性。
Moreover, the same thing that makes the virus more infectious — faster replication or tighter binding to our cells — could also make it more virulent. Indeed, some evidence suggests that Delta is more likely to result in hospitalization than other variants.
此外，使病毒更具传染性的东西——更快的复制或更紧密地与我们的细胞结合——也可能使它更具毒性。事实上，一些证据表明，与其他变异相比，德尔塔更有可能导致住院治疗。
“I could actually keep this game of imagining going on for a long time,” Dr. Read said. “On my good days, I’m optimistic that the disease severity will go down through time. Because clearly, people being isolated does affect transmission. On my bad days, I worry about it going the other direction.”
“其实这个想像游戏可以持续很长时间，”里德博士说。“在好的情况下，我乐观地认为，随着时间的推移，疾病的严重性将会下降。因为很明显，人们被隔离确实会影响传播。在不好的情况下，我担心事情会朝相反的方向发展。”
Uneasy equilibrium
不稳定的均势
Although many possible paths remain open to us, what is certain is that SARS-CoV-2 will not stop evolving — and that the arms race between the virus and us is just beginning.
虽然未来仍有许多可能性，但可以肯定的是，SARS-CoV-2不会停止演变，病毒和我们之间的军备竞赛才刚刚开始。
We lost the first few rounds, by allowing the virus to spread unchecked, but we still have powerful weapons to bring to the fight. The most notable are highly effective vaccines, developed at record speed. “I think there is hope in the fact that the SARS-CoV-2 vaccines at this point are more effective than flu vaccines have probably ever been,” Dr. Bloom said.
因为任由病毒肆意传播，我们输掉了前几轮，但我们仍有强大的武器可以投入战斗。最引人注目的是以创纪录速度开发的高效疫苗。“目前SARS-CoV-2疫苗比以往的流感疫苗都更有效，我认为这是希望，”布鲁姆说。
Even the first generation vaccines provide substantial protection against disease, and there is plenty of room to improve them by tinkering with the dosing and timing, tailoring them to new variants or developing new approaches, such as nasal sprays that may be better at halting transmission.
即使是第一代疫苗也能提供对疾病的有效保护，而且还有很大的改进空间，可以通过调整剂量和接种时机、使它们适应新的变异，或者开发新的方法，比如可能更好阻止传播的鼻腔喷雾剂。
Meanwhile, as the number of completely vulnerable hosts dwindles, and transmission slows, the virus will have fewer opportunities to mutate. One recent paper, which has not yet been reviewed by experts, suggests that rising vaccination rates may already be suppressing new mutations.
与此同时，随着完全脆弱的宿主数量减少，传播速度减慢，病毒变异的机会就会减少。最近的一篇论文（尚未经过专家评审）指出，不断上升的疫苗接种率可能已经在抑制新的突变。
And the evolution rate could also slow down as the virus becomes better adapted to humans.
而且随着病毒对人类的适应性增强，进化速度也可能放缓。
“There’s low-hanging fruit,” Dr. Lauring said. “So there are certain ways it can evolve and make big improvements, but after a while there aren’t areas to improve — it’s figured out all the easy ways to improve.”
“有一些容易达到的目标，”劳林说。“所以它有一些特定的方法可以进化，并取得很大的改善，但是一段时间后就没有可以改进的地方了——它已经找到了所有容易的改进方法。”
Eventually, as viral evolution slows down and our immune systems catch up, we will reach an uneasy equilibrium with the virus, scientists predict. We will never extinguish it, but it will smolder rather than rage.
科学家预测，最终，随着病毒进化放缓，我们的免疫系统也会赶上来，我们将与病毒达到一种不稳定的均势。我们永远不会消灭它，但它会缓慢燃烧而不会变成熊熊大火。
What that equilibrium point looks like exactly — how much transmission there is and how much disease it causes — is uncertain. Some scientists predict that the virus will ultimately be much like the flu, which can still cause serious illness and death, especially during seasonal surges.
这个平衡点到底是什么样子的——传播会有多严重，以及它会导致多少疾病——尚不确定。一些科学家预测，这种病毒最终会像流感一样，仍然会导致严重的疾病和死亡，尤其是在季节性高峰期间。
Others are more optimistic. “My guess is that one day this is going to be another cause of the common cold,” said Jennie Lavine, who explored that possibility as an infectious disease researcher at Emory University.
也有人更为乐观。“我猜，有一天它将成为普通感冒的另一个肇因，”埃默里大学(Emory University)研究这种可能性的传染病研究员珍妮·拉文(Jennie Lavine)说。
There are four other coronaviruses that have become endemic in human populations. We are exposed to them early and often, and all four mostly cause run-of-the-mill colds.
还有其他四种冠状病毒在人类中流行。我们很早并且经常接触到它们，这四种病毒主要导致普通感冒。
Covid-19 might just be what it looks like when a novel coronavirus spreads through a population without any pre-existing immunity. “This may not be such a different beast than everything else that we’re accustomed to,” Dr. Lavine said. “It’s just a bad moment.”
一种新型冠状病毒在没有预先免疫的人群中传播，可能就是新冠肺炎的情况。“这可能和我们习惯的其他病毒没有太大不同，”拉文说。“这只是情况糟糕而已。”
Of course, plenty of uncertainties remain, scientists said, including how long it will take to reach equilibrium. With infections beginning to decline again in the United States, hopes are again rising that the worst of the pandemic is behind us.
当然，科学家们说，还有很多不确定因素，包括需要多长时间才能达到平衡。随着美国的感染人数再次开始下降，人们再次燃起希望，认为疫情最严重的时期已经过去。
But much of the world remains unvaccinated, and this virus has already proved capable of surprising us. “We should be somewhat cautious and humble about trying to predict what it is capable of doing in the future,” Dr. Crotty said.
但世界上大部分地区仍未接种疫苗，而这种病毒已被证明有能力让我们大吃一惊。“预测它在未来能会怎样时，我们应该保持谨慎和谦逊，”克罗蒂说。
