Sequencing pre-1918 influenza viruses

Somehow I missed this story in the June issue of Science:

…Jeffery Taubenberger of the Armed Forces Institute of Pathology (AFIP) in Washington, D.C., said that RNA found in tissue samples from pneumonia patients who died in 1915 shows that the virus’s hemagglutinin–an all-important coat protein–is a subtype called H3. If confirmed, “that’s tremendously exciting,” says molecular biologist Ian Wilson of the Scripps Research Institute in San Diego, California. Knowing the virus’s entire genetic makeup–which Taubenberger believes is possible–would shed fresh light on where the 1918 killer flu may have originated, Wilson says.

It’s now known for certain that the 1918 “Spanish” influenza virus was serotype H1N1, due to work carried out by Taubenberger and his group sequencing and piecing together portions of the virus. (Serological studies carried out after the identification of the influenza virus had already suggested that, but the actual sequence of the virus then confirmed it). What wasn’t known previously was what serotype of virus it had replaced; in other words, what was circulating prior to 1918. Again, serological evidence provided some clues, but the actual viral sequences would provide much more information than can be gleaned by antibody studies alone. Like Taubenberger’s previous work reconstructing the 1918 virus from archived tissue specimens, this new research is using archived patient samples from 1915 at the University of London, that apparently harbor a H3 serotype virus (the neuraminidase type apparently hasn’t yet been elucidated).

The team plans to spend the next several years sequencing the entire viral genome. If viruses from before 1918 are completely different than the pandemic virus, that would support Taubenberger’s contested theory that the pandemic virus jumped directly from an avian host into the human population, says virologist Albert Osterhaus of Erasmus University in Rotterdam, the Netherlands. “This could be the clincher,” says Oxford.

Comments

#1 Lenn
July 27, 2006

Wow! That’s so cool. This could greatly expand our understanding of the history of influenza.

I wonder what the chances are of going farther back to see some of the other influenza pandemic viruses were.

This might also explain why the 1968 H3N2 pandemic was no worse than it was. Since many people in the world are descendents of the people who survived the original H3 pandemic, there would be less susceptibility to the virus than to one that had never been in the population before.

What do you guys think?
#2 Tara C. Smith
July 27, 2006

They mention they have samples from as far back as 1905. If others that are older can be located, theoretically we could go back even farther, but I’m not familiar with how frequently samples were archived at this time. I’m guessing it’s exceedingly rare.

As far as the 1968 pandemic, I don’t think it would make much of a difference. The strains circulating pre-1918 weren’t especially deadly, so I doubt they would have had much effect on selection for resistant individuals in the next generation. Immunity would be a more reasonable answer, but given the time interval, that seems rather unlikely as well, since most people who were exposed pre-1918 would have been deceased by the time it came around again in 1968. Unless an H3 virus was circulating at a low level for awhile (years? decades?) after the Spanish flu swept in–but I don’t know off the top of my head if there’s any evidence to support that (there’s none that I’m familiar with, anyway).
#3 Lamark
July 27, 2006

Yes, I think you did miss some things Tara!

Here are some of them:
http://www.sparks-of-light.org/birdflu.html

1. It presumes that the circumstances now are the same as in 1918. Viruses do not evolve in a vacuum. They are pushed to change themselves mostly when they need to do so in order to survive – in other words normally when the environment around them has become dangerous to them. (Such as when their survival is constantly threatened by the same antibiotic.)

2. The work that showed some similarity between a virus present in 1918 and the current bird flu virus rests on the unique work of one scientist and the team he leads. He examined tiny shreds of DNA recovered from the corpses of a few people who died at the time, and from these over ten years he managed to assemble something that he said was possibly similiar to today’s bird flu virus, although he also said it was clearly not the same virus.

You can read teh rest on your own!
#4 Laura
July 27, 2006

Lamark,

Antibiotics don’t kill viruses.
#5 Tara C. Smith
July 27, 2006

Lamark, have you read anything I’ve written on influenza, including this post? What you linked/quoted doesn’t have anything to do with the current post, and if you’ve read previous posts, you’ll see that I’ve never, ever suggested that anyone be “terrified” regarding H5N1–simply informed. In addition, even your summary contains many basic mistakes. For instance, you say:

1. It presumes that the circumstances now are the same as in 1918. Viruses do not evolve in a vacuum. They are pushed to change themselves mostly when they need to do so in order to survive – in other words normally when the environment around them has become dangerous to them. (Such as when their survival is constantly threatened by the same antibiotic.)

First, that’s not how evolution happens–viruses don’t “change themselves” due to a stimulus. Additionally, antibiotics aren’t used for viruses.

2. The work that showed some similarity between a virus present in 1918 and the current bird flu virus rests on the unique work of one scientist and the team he leads. He examined tiny shreds of DNA recovered from the corpses of a few people who died at the time, and from these over ten years he managed to assemble something that he said was possibly similiar to today’s bird flu virus, although he also said it was clearly not the same virus.

I’m not even sure where to start here, as again, it contains numerous errors. However, most important is your misunderstanding of what a “bird flu virus” is, it appears. No one is even close to suggesting that the avian H5N1 strain that’s getting so much attention today is the same virus that caused the Spanish influenza (which was a completely different serotype–H1N1). Rather, the other parallels are investigated–such as direct transmission from bird to human (seen in H5N1, and postulated with the 1918 H1N1 based on the sequence data); ability of both viruses to cause a “cytokine storm” and cause serious disease in the young and healthy; overall unusually high mortality rate, etc.

I’ll point you to this series of posts I wrote on it last year (somewhat dated, it should be noted), and also to the Flu Wiki, which has all kinds of excellent information, as places to start investigating this.
#6 Lamark
July 27, 2006

Thank you Tara for the “Flu Wiki”! But I would not waste my time, as it will be the collection of facts from the WHO and CDC, I assume, and I will just read those pages where the propoganda orignates.

I agree with the post that corrects the statement, that viruses are challenged by antibiotics. This is from the page that I drew the passages from, which I hoped you would read, but I think you did not!

yes, that is an interesting statment.

“They are pushed to change themselves mostly when they need to do so in order to survive – in other words normally when the environment around them has become dangerous to them. (Such as when their survival is constantly threatened by the same antibiotic.)”

I wonder what the writer intends? One would have to read the entire work to understand. Perhaps she has an insight into virology that would benefit all of us?

Ah! When one reads her entire post, there is more information. I will not put all of it here, of course, I will hope that you can read that page from the link, but I will help you read a bit more.

http://www.sparks-of-light.org/birdflu.html

The First Point. Just what was happening at the time of the 1918 epidemic that might force viruses to mutate – or otherwise cause a terrible epidemic? My suspicions got alerted when I found that the epidemic had started on the Western Front during that dreadful war where millions were being killed, where poison gas was being widely used, and some very crude polluted vaccines widely employed, and had ended when that war ended! The BBC even managed to discover the very military camp at the Western front where it thought it started.

If ever there was a time when a virus might be forced to mutate, that was then – and it is not now. There is no comparison with our lives now in the west – although it should be mentioned that there is much pollution in the East where these birds are mostly falling ill.

We should also not ignore the possibility that the immune systems of the men at the front by 1918 was starting to be gravely affected by the accumulation over several years of toxins from poison gases and many other souces in the blood and tissues – for that is how toxins work. They can accummulate in our vital organs until they get to the point of causing our immune systems and other systems to collapse. At this point, we may not even have the strength to deal with a virus or bacteria – or fungus – that wouild normally not make us seriously ill at all.

So – is there any evidence for this being how the epidemic started, did it really come from the Western front. Well yes there is. The Swiss particularly suspected that this was what was happening – and published medical papers on it. Here is a graph showing how the epidemic peaked in the final months of the war and then ended. The Swiss found the returning soldiers were giving it to wives and girl friends – but the main people falling ill were the soldiers.

That is all friends, until tomorrow!
#7 Chuck Darwin
July 27, 2006

I really enjoy this blog and find Tara’s posts and efforts in the comments to be of consistent interest and eloquence. I want to pose to readers (including Tara) an ethical question I have been dealing with as a virologist for the past few years. I actually work with filoviruses, but I have many colleagues who work on influenza, including some work on the 1918 virus, so I’m very familiar with the virus’s structure and pathogenesis. The work Taubenberger and others are doing on the evolution of influenza a century ago is fascinating and could very well be pertinent to prediciting future influenza virus genetic drift/shift, host-virus interactions, etc. However, I ask myself if the benefits of this work for future public health, as well as for general scientific interest, is worth the risks when it comes to biosecurity. With reverse genetics methods introduced a few years ago, any influenza virus can be generated through relatively common, albeit cumbersome, molecular biological techniques. For someone with a solid background in molecular biology and the ability to read the average materials and methods section, it would only take the proper resources to generate any strain someone wanted.

This concern extends to other viruses. I have a real problem with the sequence of smallpox being determined and made publicly available, as, once again, tedious but straightforward cloning techniques are now available to, in theory, produce smallpox virus “from scratch”. In short, I am curious what everyone here thinks about these issues. Is the human “need to know”, a trait that is particulary strong in scientists, going a little too far in some facets of biology? Should the virology community be making a greater effort to discuss the ethical and security implications of their work? Self-regulation in the early stages of recombinant DNA technology was very impressive. Have we lost our way while technology speeds forward?
#8 Todd
July 27, 2006

And we all know what happens when we assume, right Lamark?
#9 Rachel
July 27, 2006

Lamark, I don’t think you should waste your time on the scientific ‘evidence’ put into that article. She isn’t exactly a scientist herself. There are more than a few things I have a problem with in that article. Don’t trust everything you read on the internet.
#10 revere
July 27, 2006

Lamark: The link you posted is so full of misinformation it is hard to know where to start, so I’ll just point out a couple of major errors that indicate little knowledge of the subject on the writer’s part. Influenza is an RNA virus, not a DNA virus. Viruses are not caused to mutate by their environment. They mutate on their own and are selected by their environment. Antibiotics cause no selection. All the stuff about the troops and the Western Front has been gone over by many people and are not relevant. BTW The Flu Wiki (of which I am one of the founding editors) has several thousand pages of content, most of which are not from CDC or WHO.

Tara’s got it exactly right. You’ve got it completely garbled. What exactly is your point?
#11 Bolan
July 27, 2006

Lamark, yet even another point of inaccuracy on Sparky’s webpage is the origin of the pandemic. It had been spreading west-northerly from SE Asia for a year and a half or two (IIRC) before it was able to take advantage of the war in Europe.
#12 HCN
July 27, 2006

Lamark: You need to step away from the computer, not get information from the Internet and go to you nearest library. Check out the following books:

Flu: The Story of the Great Influenza Pandemic by Gina Kolata ..
http://www.amazon.com/gp/product/0743203984/
and
The Great Influenza by John Barry…
http://www.amazon.com/gp/product/0670894737

The both cover different parts of the 1918 pandemic… and both are really good books.
#13 spudbeach
July 27, 2006

Chuck Darwin:

I don’t know where I stand on your issue — it’s certainly arguable. But, I think we need to factor in the inevitability of knowledge: if we don’t discover the dna/rna sequence of all the nasty bugs, somebody else will, and we’ll be right back to where we are now.

Should we be working on something else, more directly related to influenza safety? I would say that a better way of making flu vaccines would be nifty (taking one chicken egg to make three doses is ridiculous), but in science, one doesn’t always get to pick and choose. Yes, I’m scared of the thought of viruses being made from scratch (polio already has), but if you stop and think, you can scare yourself of anything. Best to just keep plowing along and hope everything works out for the best.
#14 Dior
July 28, 2006

To Chuck Darwin. I am a virologist and also colaborate with Ian. Your post about genomes being published and the risk it entails is a good point. I would counter point that with modern methods and genomic information, it is more efficient to try and make vaccines and small molecule or even siRNAs to combat the pathogen. If you have the ability to make a bug bomb, you can probably eek out enough of the esquence to do so.
#15 Tara C. Smith
July 28, 2006

Hi Chuck,

First–you work on filoviruses? How cool!

I started answering you here, but I think the question is too interesting to be buried here in the comments, so I’m starting it as a new post.
#16 mgr
July 28, 2006

I may be a little dense, and more than a little ignorant–but can someone explain how a pneumonia case can yield influenza virus? There just not enough here in the post to separate a viral pneumonia and influenza (unless the capsule/coat protien is unique to flu–but that begs the question). I understand that following flu, secondary infections occur that include pnuemonia, but one thing about the period in time is the ubiquity of pneumonia in Europe.

Mike
#17 Tara C. Smith
July 31, 2006

Mike, I’m not 100% sure what you’re asking.

Pneumonia can be caused by a variety of pathogens–bacteria, fungi, viruses. In many cases, influenza causes lung damage that allows bacteria to more easily colonize the lungs, leading to bacterial pneumonia, but it can also cause a primary pneumonia, which is due to the influenza virus itself. In the case of the 1918 samples, they come from 2 different places–from soliders who died of primary viral pneumonia (they succumbed quickly to the disease, and bacteria weren’t found in their lungs, I believe), and from a woman unearthed in Alaska, in a town that was hit hard by the pandemic. So these samples were identified based largely on their symptoms and history, and RNA was extracted from the samples. Influenza-specific primers were then used to amplify the viral RNA the samples contained.
#18 mgr
July 31, 2006

Tara–Thanks for the clarification, you answered it. Essentially I was looking for the methodology that assured that what they recovered was influenza.

Mike
#19 youtube
January 17, 2008

BTW The Flu Wiki (of which I am one of the founding editors) has several thousand pages of content, most of which are not from CDC or WHO.
#20 youtubedizi
February 7, 2008

BTW The Flu Wiki (of which I am one of the founding editors) has several thousand pages of content, most of which are not from CDC or WHO.