October 28, 2004
1918 Killer Flu Virus Research Lab Containment Levels Too Low?

The 1918 influenza virus pandemic that killed tens of millions of people is being reconstructed in research laboratories using virus samples extracted from the long frozen bodies of victims of the virus who were buried in very cold regions of far northern Europe. While some of the work on these virus samples were done in a top level BioSafety Level 4 (or BSL-4 or BSL4) level laboratory much of the work on the 1918 influenza is being done in lower level BSL-3Ag and even lower level BSL-3 labs. (same article here)

Yet despite the danger, researchers in the US are working with reconstructed versions of the virus at less than the maximum level of containment. Many other experts are worried about the risks. “All the virologists I have spoken to have concerns,” says Ingegerd Kallings of the Swedish Institute for Infectious Disease Control in Stockholm, who helped set laboratory safety standards for the World Health Organization.

If a virus that killed 40 million people is not worthy of being handled in top level of containmen then what is? I guess an argument can be made that smallpox is an even greater threat and warrants an even higher level of caution. But I'm not even sure that is true. My guess is we are far better equipped to stop a smallpox outbreak than to stop an influenza outbreak.

By contrast, the team in Georgia, the first to experiment with genetically engineered 1918 viruses, did all its work at BSL-3Ag. Meanwhile, Michael Katze at the University of Washington at Seattle is planning to expose monkeys to aerosols of 1918-type viruses at BSL-3, a step down from BSL-3Ag. The recent SARS escapes were from BSL-3 labs.

Some scientists are less worried that the bioengineered viruses being worked with are that big of a potential threat.

The head of the World Health Organization's global influenza program said he isn't certain that work on the virus needs to be restricted to the most secure facilities, but the agency would be open to hosting a forum on the issue.

"What we mustn't forget is that what they're working on is not the 1918 virus," Dr. Klaus Stohr cautioned in an interview from Geneva.

The 1918 flu epidemic (sometimes called the Spanish flu though it probably didn't originate in Spain) killed somewhere between 20 and 40 million people. The estimates of mortality are broad because there are no reliable statistics on deaths in much of the world and death rates in differed greatly. But an assumption that about 2% of the world's population died is not unreasonable. My guess is that an influenza outbreak that happened today with similar mortality rates would probably kill between 60 million and 150 million people. Of course in the more developed countries public health mesures such as quarantines and protective gear would reduce the death rates considerably. Yet most people do not live in developed countries. Also, after the first season of outbreak a vaccine might be able to be produced that would halt it in at least parts of the world.

Currently a building boom in BSL-3 and BSL-4 labs is underway mainly in reaction to the 9/11 terrorist attack and the anthrax attack that followed it.

Altogether, the nation's combined total of BSL-4 lab space, 1,689 square meters, "is extremely limited and obviously insufficient," says Stephen Morse, director of Columbia University's Center for Public Health Preparedness. To remedy such shortages, NIAID awarded grants of about $120 million each in October 2003 to help pay for new BSL-4 labs at Boston University and a second, much larger lab at UTMB. Together they will add 3,925 square meters, more than twice the current amount of space.

In addition, NIAID is planning to build two BSL-4 labs for its employees, one in Hamilton, Montana, (which is now undergoing an environmental assessment) and the other in a new National Interagency Biodefense Campus at USAMRIID. They will add 2,879 square meters, almost twice as much as exists now. In addition, the CDC plans to build 1,275 square meters of new BSL-4 space in Atlanta.

But all those labs take 5 to 10 years to become available.

We need for scientists to figure out what made the 1918 so deadly. Another influenza strain could mutate into that level of lethality at any time. Would convention influenza vaccine development techniques work against the 1918 strain? We need to find out. So the research work is very much worth doing.

An important aside to this report is that we need more rapid techniques for making influenza vaccines. The latest problem with contamination of 48 million doses of Chiron Corporation's influenza vaccine highlight the problem with the current method of making influenza vaccines in specially produced chicken eggs. Influenza vaccine production takes 6 months and can not easily be scaled up to handle a known large scale outbreak.

The quaint system of producing flu vaccine based on seasonal egg-laying has harsh implications for what would happen if new batches had to be made in a hurry to fight a super-strain pandemic. At best, it would take half a year.

We need very rapid techniques for producing flu vaccine.

It is only a matter of time before a new highly deadly flu strain arises that rivals or surpasses the 1918 pandemic in deadliness.

Monica Schoch-Spana, a senior fellow at the Center for Biosecurity of the University of Pittsburgh Medical Center, said the likelihood of an upcoming flu pandemic is "not a matter of if, but when."

Also see my previous post Sequencing Of 1918 Spanish Flu DNA Increases Risk Of Bioterrorism.

Share |      Randall Parker, 2004 October 28 04:20 PM  Dangers Natural Bio

Steel Turman said at October 28, 2004 9:55 PM:

I agree there is bad judgement here in the levels of isolation, but do not the last 9 decades of
influenza mitigate on a viral level the intensity of the 1918 pandemic?

Larry Borsato said at October 29, 2004 7:03 AM:

An all too realistic novel called The First Horsemen by John Case details a situation where the 1918 Spanish Flu is made more virulent and the distributed via aerosolization offshore by infecting bird carriers. Even if we knew the strain of influenza and developed an anti-virus, the death toll would be extremely high before any flu shots could be made available. Terrorists could also engineer and distribute several other decoy strains at the same time to cause confusion.

When I heard of SARS my first thought was that it might have been a very effective test of a bio-terrorist weapon - or a test gone horribly wrong.

jason said at October 29, 2004 6:09 PM:

this strikes me as foolish. you wouldn't want to find out the hard way how the virus would behave today.

Kurt said at October 29, 2004 8:02 PM:

Making an artifical virus is getting easier and cheaper all the time. You can order DNA sequences off of the internet and splice them together using a synthesizer. If the design is right, cultivating the results in human cell culture will result in the designed virus spontaneously self assembling. Self assembly. Kind of like nanotechnology, only this is real.

The polio virus has 7,000 base pairs and, therefor, was the first to be made from scratch this way. Smallpox, on the other hand, has 180,000 base pairs and is much more difficult to fabricate from scratch. Influenza is somewhere in the middle, with 18,000 base pairs. Ebola has 70,000 base pairs.

Does anyone here know specifically what determines if a virus can be transmitted by air (like flu) or must be transmitted by blood (like ebola and HIV)? Perhaps it is the thickness and the molecular design of the protein coating. I know that verulence is largely determined by the molecular ends of the "spikes" (the viruses that look like old-fashioned marine mines) which bond to recepters in the host cells. The genes that code for these in flu viruses are known and are used to catagorize the virus (e.g. H5N1, etc.). There are usually 8 genes in the flu virus, including the two responsible for infection.

The glycoprotein gene in ebola is also known and is responsible for the "bleeding" effect that occurs in patients.

Can this glycoprotein gene be inserted in a flu virus and thr expression of this gene not interfere with the infectousness or self-replication of the virus? Who knows?

Viruses that do not kill the host can spread much more effectively than those that do. What about an airborne virus that does not kill, but only makes sterile (infertile)? Again, noone knows.

Ed said at October 30, 2004 8:59 PM:

For all of the fears of an engineered virus, I think there is one key point. Any 'sane' actor who plans to release an engineered virus into a population w/ no native defenses would want a tested vaccine prior to release. This suggests to me that it is something that will be difficult to do by small terrorist organizations. Assuming the upper echelons would like to survive, they would want a vaccine for themselve, their relatives, their lackeys, their wives and children. The only way to accomplish this is by testing on humans. To develop a weapon, you need human testing.
For human testing you need a society where 'disposable' humans exist. Iran & No. Korean for example. In those societies, you have the engineering talent, the ability to use humans for experimentation and probably the political will.
I really fear a concerted effort by one of these nations to develop a weapon out of something like the flu.

Randall Parker said at October 30, 2004 9:06 PM:


Two points:

1) An engineered virus could get released accidentally. There have already been accidental infections of SARS from labs.

2) We have to worry that eventually an influenza virus in the wild will mutate into a form that will kill tens of millions just like happened in 1918.

So intentional release of an engineered virus is only one of the biological threats we face.

We sure need a faster way to develop and produce vaccines...

Kurt said at October 31, 2004 10:37 AM:

Entirely new vacines can be cultured and developed in human cell cultures and distributed to the public with-in 6 months. The problem is with government bureaucracy and FDA regulation. In the case of a "slate-wiper", I don't think government edicts are going to count for much and that many companies will simply develop their own vaccines and sell them to the public.

A "slate-wiper" will burn through the global population quite fast (6 months) and then disappear, along with a sizable portion of the human population. Getting food production back on line will require an additional year (depending on the growing season and its length). So, a two year supply of canned and freeze-dried food (along with "anti-aging" vitamin suppliments) is most desired for riding one of these things out.

The benefit of a post-plaque economy will be the labor shortages. Noone is ever going to tell you that you are "not qualified" for the job.

Tom Mazanec said at December 16, 2004 7:57 AM:

Didn't they do something to the mousepox virus that made it a "slate-wiper"? like inserting an interferon gene? It is a couple years ago, so I am hazy on the details.

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