Peter Palese has written an excellent opinion piece for the Wall Street Journal on why swine flu is not that scary. His arguments may bring some comfort for those readers of virology blog who are worried about the impact of the new influenza H1N1 strain. Even if you are not worried, the scientific basis for his arguments are compelling and answer some of the many questions I have been receiving in the past week. I can’t think of anyone’s opinion on influenza virus that I value more – and it’s not just because I did my Ph.D. research in his laboratory. He’s an outstanding scientist with balanced, well-informed opinions. Herewith are some excerpts from his piece.
First, Palese reviews the concerns about the new H1N1 viruses:
1. The swine virus belongs to the same H1N1 group as did the 1918 pandemic virus.
2. The swine virus is readily transmitted from human to human. At this point, swine virus isolates have been reported on four continents. The avian H5N1 virus (another virus with pandemic potential) was never proven to readily transmit from person to person; rather, humans were probably infected directly from chickens and these infections required large quantities of virus.
3. The swine virus shows an unusual robustness in emerging outside the normal seasonal period for the virus. Influenza viruses are rarely isolated at the end of April in the northern hemisphere, and winter hasn’t yet started in New Zealand, where several isolates have already been reported.
4. Mutations and/or acquisition of genes derived from other human or animal influenza viruses could make the swine virus into something much more virulent than it is now. Mutations and acquisition of genes are natural processes for influenza viruses against which there are no man-made interventions. Furthermore, these processes (and the extent to which they could enhance virulence) cannot be predicted.
Next, he argues why we should be optimistic:
1. In 1976 there was a an outbreak of an H1N1 swine virus in Fort Dix, New Jersey, which showed human to human transmission but did not go on to become a highly virulent pandemic strain.
2. The presently circulating swine virus is most likely not more virulent than the other seasonal strains we have experienced over the last several years.
3. The current swine virus lacks an important molecular signature (the protein PB1-F2) which was present in the 1918 virus and in the highly lethal H5N1 chicken viruses. If this virulence marker is necessary for an influenza virus to become highly pathogenic in humans or in chickens, then the current swine virus doesn’t have what it takes to become a major killer.
4. Since people have been exposed to H1N1 viruses over many decades, we likely have some cross-reactive immunity against the swine H1N1 virus. While it may not be sufficient to prevent becoming ill, it may very well dampen the impact of the virus on mortality. I would postulate that by virtue of this “herd immunity” even a 1918-like H1N1 virus could never have the horrific effect it had in the past. The most likely outcome is that the current swine virus will become another (fourth) strain of regular seasonal influenza.
5. The landscape of vaccines and anti-influenza drugs has dramatically improved over what it was just a few years ago. Based on what we know of the structure and sequence of the swine virus, these FDA-approved drugs and FDA-licensed vaccines (modified to include the swine strain) would be highly effective against this new virus. Also, present technologies as well as manufacturing capacities will allow us to make sufficient quantities of a swine virus vaccine for the winter 2009-10 season in this country.
In closing, he notes that we have a vastly improved infrastructure to deal with novel emerging diseases:
The preparedness plans developed against the H5N1 influenza threat dramatically improved overall surveillance (we would probably not have learned so fast about the swine virus were it not for these improved capabilities). Major advances have been initiated by our government to develop new and improved manufacturing processes and exciting new vaccine and antiviral approaches are also in the pipeline, and they show promise of tipping the balance in favor of humans against a devious virus. For example, universal influenza vaccines (one long-lasting vaccine against all strains) and broadband antivirals are being developed in our academic laboratories and in innovative small biotech companies. This work has been primarily funded by the NIH and the CDC and it will pay off by diminishing the future impact of influenza on the health of our citizens and on the economy of our country. It is prudent to prepare against swine influenza, but equally important to keep a balanced outlook and an awareness of our current capabilities.
Coming from such a well-informed and experienced source, these arguments are compelling. Please pass them on to anyone you know who might be worried by the recent emergence of the new influenza H1N1 virus.
Comments on this entry are closed.
“The current swine virus lacks an important molecular signature (the protein PB1-F2) which was present in the 1918 virus and in the highly lethal H5N1 chicken viruses. If this virulence marker is necessary for an influenza virus to become highly pathogenic in humans or in chickens, then the current swine virus doesn’t have what it takes to become a major killer.”
Is Dr. Palese taking into account those Mexican isolates that you say haven't been publicized? Or does this matter?
I'm not sure if he has seen the Mexican isolates. I will ask him next
week – I'm doing a special edition of TWiV early in the week.
I would like to direct everyone to the first hour of Science Friday on NPR from 5/1/2009. There is a very good conversation with Dr. Fauci from NIADI that complements the Dr. Palese article. There is also an interesting conversation with Dr. Markel from University of Michigan about the use of quarantine in the 1918 outbreak and the recent measures taken by Mexico and the US. Here is the link, http://www.sciencefriday.com/program/archives/2….
Thank you; I look forward to seeing it. This “omission” strikes me as a huge gap in the public record of this illness and its transmission.
And how do 3 million homeless people in the USA alone fit into this 'nothing to worry about' picture?
http://en.wikipedia.org/wiki/Homelessness_in_th…
This is a very helpful counterpoint to the mainstream media's siren song. I will use it, along with the article by Dr. Larry Brilliant in the WSJ's “Weekend Edition” in my summer and fall homeland security concepts course. In addition to the virology and public health aspects of this, I always insist the class studies (and critically interacts with) the way the media behaves during any emergency. Unfortunately we can't just “do the science” regarding something like this; professionals also have to “do the media.”
This is reassuring:
“Nicholas Grassly of Imperial College London and Andrew Rambaut of the University of Edinburgh, UK, have analysed the rate of spread. Their analysis is based on the small mutations that have accumulated in almost two dozen genetic sequences produced so far, from viruses collected from patients in Mexico and the US.”
http://www.newscientist.com/article/dn17072-fir…
but…..”In contrast to H5N1 bird flu, all the genetic sequences of this H1N1 are being posted on bulletin boards like GISAID”
All?
I would keep my eyes on Brazil. Brazil is poor and pathogenic – like 10 Mexicos.
This is reassuring:
“Nicholas Grassly of Imperial College London and Andrew Rambaut of the University of Edinburgh, UK, have analysed the rate of spread. Their analysis is based on the small mutations that have accumulated in almost two dozen genetic sequences produced so far, from viruses collected from patients in Mexico and the US.”
http://www.newscientist.com/article/dn17072-fir…
but…..”In contrast to H5N1 bird flu, all the genetic sequences of this H1N1 are being posted on bulletin boards like GISAID”
All?
I would keep my eyes on Brazil. Brazil is poor, pathogenic and in the Southern Hemisphere – like 10 Mexicos.
“. The current swine virus lacks an important molecular signature (the protein PB1-F2) which was present in the 1918 virus and in the highly lethal H5N1 chicken viruses. If this virulence marker is necessary for an influenza virus to become highly pathogenic in humans or in chickens, then the current swine virus doesn’t have what it takes to become a major killer.”
Regarding this marker – is it something that was present as well in the early wave of the 1918 virus, which was also considered mild up until August, or was it something that was acquired during its passage through humans?
Do the steps being currently taken reduce the likelihood of sufficient human-to-human transmission to adapt and become more virulent?
It's a good question. The 1918 sequences were obtained from autopsy
material collected in September and November of 1918. Therefore we
can't address the question of whether any changes occurred during
propagation in humans.
We can reduce but not eliminate transmission; therefore selection for
viruses of greater virulence is still possible.
Yes, the Mexico H1N1 sequences have been posted to GISAID. I see 30
isolates so far there.
is the swine flu really scary.? can it kill you the minute you get it.?
do doctors have the swine flue under control.?
Dear Professor Vincent Racaniello.
I have taken the liberty of making a loose translation summation of this article into Japanese for post on the linked blog. Toegether with your interview of Dr. Palese, it is the most informative and reassuring (though cautiously so) article I have come accross. Please would you be so kind as to let me know if you want me to take it down. I have cited you fully. The post will appear here soon.
http://www.butainfuru.com/2009/05/h1n1_2170.html
Thank you for making the translation. I have no problem at all with
you posting the material on your site, as long as virology blog is
cited.
That's really a fantastic post ! I added to my favorite blogs list..
I have been reading your blog last couple of weeks and enjoy every bit good info about swine flu. Thanks
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Here is a Chinese edition of this article translated by Prof. Jiaxin YAN:
This article was cited by many websites in China and it is helpful for Chinese to have correct opinion on this pandemic influenza.
美院士帕雷斯:甲型H1N1流感危害不会特别大
2009年05月05日10:13 来源：环球科学 文：严家新
2009年，5月2日，美国病毒学会会长、美国科学院院士、全球顶级流感专家彼得·帕雷斯（Peter Palese ）在美国《华尔街日报》（Wall Street Journal）撰文认为：猪流感（甲型H1N1流感）危害不会特别大（原文标题为：Why Swine Flu Isn't So Scary，直译为《为什么猪流感不是那么可怕》）。
帕雷斯院士作为全球顶级流感专家，多年来一直强调：对未来流感大流行的准备工作还没有获得足够的关注。但是在面对具体的某个流感毒株造成大流行的可能威胁时，他却总是能凭籍渊博的学识，通过全面系统的分析论证，提出可能与众不同、但最终被证明是正确的观点。一个最典型的例证就是：自从1997年香港H5N1禽流感流行以来，帕雷斯院士是H5N1可能导致流感大流行假说的最强烈反对者之一。十余年来的事实证明他基本上是对的，香港H5N1禽流感一直未造成全球大流行。
理论上，猪流感引发大流行的可能性比禽流感要大得多，帕雷斯也是持这种观点的。这次的猪流感在从首例确诊开始不到一个月的时间内，就达到了世界卫生组织5级警告的水平，并有可能上升到6级（最高级别）。这是否证明了帕雷斯上述理论的正确，表明确实有一次危害相当于1918年猪流感的新的猪流感大流行就要到来呢？帕雷斯院士没有因为自己的理论初步得到验证而得意忘形，经过冷静的系统分析，帕雷斯院士在《华尔街日报》的这篇文章中以令人信服的科学依据作出最新预测：结果不可能那么糟，我们完全有理由更加乐观。
当然，帕雷斯院士说当前的猪流感危害不会特别大，并不是说当前不要防控这种流感了。帕雷斯的观点可以换一种我们更熟悉的表述方式：我们有充分的科学依据在战略上藐视敌人，但与此同时，在战术上仍要重视敌人。我们应当有充分信心：人类积极、科学的应对完全可以将流感大流行的损失降到最小。
帕雷斯院士多年来一直担任美国纽约西奈山医学院微生物学系主任。他从上世纪80年代起就经常访问中国（包括武汉）。1987－1989年，我曾在帕雷斯院士的实验室做流感方面的博士后研究。在这篇《华尔街日报》的这篇文章中，帕雷斯院士首先对新的H1N1病毒的主要特点进行了总结：
1.这种猪病毒与1918年的大流行病毒属于相同的H1N1亚型。
2. 猪病毒很容易实现人际间传播。目前，猪病毒株已出现在4大洲。从未证明禽流感H5N1病毒（另一种有流行潜力的病毒）容易实现人际间传播；人可能是直接从鸡感染H5N1病毒，这种感染需要大量病毒才能实现。
3. 这种猪病毒在它们通常出现的季节以外的季节出现，这是不正常的。流感病毒很少在4月底在北半球分离到；而目前在新西兰则冬季尚未开始，但在那里也报告分离到数个毒株。
4. 猪病毒经由突变和/或从其他人或动物流感病毒获取新的基因，可以变得比它们目前所表现的致病性更强。对流感病毒来讲，突变和获取外来基因是自然发生的过程，其中不存在任何人为的干预。而且，这些进程（以及它们的毒性会增强到什么程度）无法预测。
帕雷斯还以严密的论证，告诉我们为什么应该乐观：
1. 1976年，在新泽西州迪克斯堡曾发生过一次H1N1猪病毒的爆发，该病毒曾发生过人际间传播，但最终并没有成为一种非常致命的大流行株。
2. 目前流行的猪病毒与我们在过去若干年里经历过的其他季节性流感毒株相比，其毒力很可能并不是更强。
3. 目前的猪病毒缺乏一个重要的分子标志（病毒内部蛋白PB1 上的 F2片段）， 这是在1918年的病毒和高致病性的H5N1禽流感病毒中都存在的。如果一种流感病毒要想对人类或对鸡具有高致病性，此毒力标志确实是必要的，那么目前的猪病毒就缺少能成为一个主要杀手的基本条件。
4. 因为人类在过去数十年来一直暴露于H1N1病毒，我们可能有一些针对猪H1N1病毒的交叉免疫力。虽然这种免疫力可能不足以防止患病，但很可能能降低病毒引起的死亡率。帕雷斯推断，由于人群中这种“群体免疫”的存在，即使是出现类似1918年H1N1的病毒，它也绝不可能引发它曾经引发过的那么可怕的后果。最有可能的结果是，当前的猪病毒将演变成为另一种（第四种）常规的季节性流感毒株。
5 .疫苗和抗流感药物的技术平台比起几年前已大大改善。根据我们所知道的猪病毒的结构和序列，目前美国食品及药物管理局已批准的药品和已获注册的疫苗（稍经修改即可适用于猪流感毒株）对付这一新的病毒将是非常有效的。此外，目前的技术以及生产能力将使我们能够有足够数量的猪病毒疫苗在2009-10这个冬季供应全国。
最后，他指出，我们有大量得到改进的基础设施，以应对新出现的疾病。
针对H5N1禽流感威胁实施的各项计划和预案，大大改进了整个监测系统（如果没有这些改进的监测系统，我们可能不会这么快就发现了这次的猪病毒）。最主要进展是我们的政府已着手发展新的和改进的制造工艺，令人振奋的新疫苗和抗病毒药物的开发也正在不断向前推进，结果让人类在与狡猾病毒的斗争中很有希望占上风。例如，通用流感疫苗（1 种长期对所有毒株有效的疫苗）和广谱抗病毒药物正在我们的实验室和创新的生物技术公司开发。这项工作的主要经费由美国国立卫生研究院和疾病预防控制中心提供。这种投入是值得的，结果将减少未来流感对公民健康和整个国民经济的冲击。我们当然应当审慎地准备对付猪流感，但同样重要的是要保持一种平衡的心态，充分认识我们目前已具备的能力。
（本文作者：严家新教授是武汉生物制品研究所博士生导师，主要从事狂犬病毒、人免疫缺陷病毒、丙型肝炎病毒检测和诊断试剂的研究。文中提到的美国科学院院士帕雷斯曾是严家新教授的博士后导师。）
Here is a Chinese edition of this article translated by Prof. Jiaxin YAN:
This article was cited by many websites in China and it is helpful for Chinese to have correct opinion on this pandemic influenza.
美院士帕雷斯:甲型H1N1流感危害不会特别大
2009年05月05日10:13 来源：环球科学 文：严家新
2009年，5月2日，美国病毒学会会长、美国科学院院士、全球顶级流感专家彼得·帕雷斯（Peter Palese ）在美国《华尔街日报》（Wall Street Journal）撰文认为：猪流感（甲型H1N1流感）危害不会特别大（原文标题为：Why Swine Flu Isn't So Scary，直译为《为什么猪流感不是那么可怕》）。
帕雷斯院士作为全球顶级流感专家，多年来一直强调：对未来流感大流行的准备工作还没有获得足够的关注。但是在面对具体的某个流感毒株造成大流行的可能威胁时，他却总是能凭籍渊博的学识，通过全面系统的分析论证，提出可能与众不同、但最终被证明是正确的观点。一个最典型的例证就是：自从1997年香港H5N1禽流感流行以来，帕雷斯院士是H5N1可能导致流感大流行假说的最强烈反对者之一。十余年来的事实证明他基本上是对的，香港H5N1禽流感一直未造成全球大流行。
理论上，猪流感引发大流行的可能性比禽流感要大得多，帕雷斯也是持这种观点的。这次的猪流感在从首例确诊开始不到一个月的时间内，就达到了世界卫生组织5级警告的水平，并有可能上升到6级（最高级别）。这是否证明了帕雷斯上述理论的正确，表明确实有一次危害相当于1918年猪流感的新的猪流感大流行就要到来呢？帕雷斯院士没有因为自己的理论初步得到验证而得意忘形，经过冷静的系统分析，帕雷斯院士在《华尔街日报》的这篇文章中以令人信服的科学依据作出最新预测：结果不可能那么糟，我们完全有理由更加乐观。
当然，帕雷斯院士说当前的猪流感危害不会特别大，并不是说当前不要防控这种流感了。帕雷斯的观点可以换一种我们更熟悉的表述方式：我们有充分的科学依据在战略上藐视敌人，但与此同时，在战术上仍要重视敌人。我们应当有充分信心：人类积极、科学的应对完全可以将流感大流行的损失降到最小。
帕雷斯院士多年来一直担任美国纽约西奈山医学院微生物学系主任。他从上世纪80年代起就经常访问中国（包括武汉）。1987－1989年，我曾在帕雷斯院士的实验室做流感方面的博士后研究。在这篇《华尔街日报》的这篇文章中，帕雷斯院士首先对新的H1N1病毒的主要特点进行了总结：
1.这种猪病毒与1918年的大流行病毒属于相同的H1N1亚型。
2. 猪病毒很容易实现人际间传播。目前，猪病毒株已出现在4大洲。从未证明禽流感H5N1病毒（另一种有流行潜力的病毒）容易实现人际间传播；人可能是直接从鸡感染H5N1病毒，这种感染需要大量病毒才能实现。
3. 这种猪病毒在它们通常出现的季节以外的季节出现，这是不正常的。流感病毒很少在4月底在北半球分离到；而目前在新西兰则冬季尚未开始，但在那里也报告分离到数个毒株。
4. 猪病毒经由突变和/或从其他人或动物流感病毒获取新的基因，可以变得比它们目前所表现的致病性更强。对流感病毒来讲，突变和获取外来基因是自然发生的过程，其中不存在任何人为的干预。而且，这些进程（以及它们的毒性会增强到什么程度）无法预测。
帕雷斯还以严密的论证，告诉我们为什么应该乐观：
1. 1976年，在新泽西州迪克斯堡曾发生过一次H1N1猪病毒的爆发，该病毒曾发生过人际间传播，但最终并没有成为一种非常致命的大流行株。
2. 目前流行的猪病毒与我们在过去若干年里经历过的其他季节性流感毒株相比，其毒力很可能并不是更强。
3. 目前的猪病毒缺乏一个重要的分子标志（病毒内部蛋白PB1 上的 F2片段）， 这是在1918年的病毒和高致病性的H5N1禽流感病毒中都存在的。如果一种流感病毒要想对人类或对鸡具有高致病性，此毒力标志确实是必要的，那么目前的猪病毒就缺少能成为一个主要杀手的基本条件。
4. 因为人类在过去数十年来一直暴露于H1N1病毒，我们可能有一些针对猪H1N1病毒的交叉免疫力。虽然这种免疫力可能不足以防止患病，但很可能能降低病毒引起的死亡率。帕雷斯推断，由于人群中这种“群体免疫”的存在，即使是出现类似1918年H1N1的病毒，它也绝不可能引发它曾经引发过的那么可怕的后果。最有可能的结果是，当前的猪病毒将演变成为另一种（第四种）常规的季节性流感毒株。
5 .疫苗和抗流感药物的技术平台比起几年前已大大改善。根据我们所知道的猪病毒的结构和序列，目前美国食品及药物管理局已批准的药品和已获注册的疫苗（稍经修改即可适用于猪流感毒株）对付这一新的病毒将是非常有效的。此外，目前的技术以及生产能力将使我们能够有足够数量的猪病毒疫苗在2009-10这个冬季供应全国。
最后，他指出，我们有大量得到改进的基础设施，以应对新出现的疾病。
针对H5N1禽流感威胁实施的各项计划和预案，大大改进了整个监测系统（如果没有这些改进的监测系统，我们可能不会这么快就发现了这次的猪病毒）。最主要进展是我们的政府已着手发展新的和改进的制造工艺，令人振奋的新疫苗和抗病毒药物的开发也正在不断向前推进，结果让人类在与狡猾病毒的斗争中很有希望占上风。例如，通用流感疫苗（1 种长期对所有毒株有效的疫苗）和广谱抗病毒药物正在我们的实验室和创新的生物技术公司开发。这项工作的主要经费由美国国立卫生研究院和疾病预防控制中心提供。这种投入是值得的，结果将减少未来流感对公民健康和整个国民经济的冲击。我们当然应当审慎地准备对付猪流感，但同样重要的是要保持一种平衡的心态，充分认识我们目前已具备的能力。
（本文作者：严家新教授是武汉生物制品研究所博士生导师，主要从事狂犬病毒、人免疫缺陷病毒、丙型肝炎病毒检测和诊断试剂的研究。文中提到的美国科学院院士帕雷斯曾是严家新教授的博士后导师。）