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"After consulting the leading economists of his day about where the economy was going and getting a constant stream of forecasts of 'On the one hand this and on the other hand that,' Harry Truman allegedly said, 'Hell, what I need is a one-armed economist.' "  -- Time magazine.

These words were uttered by the plain-speaking, no-nonsense Harry S. Truman during his presidency.  They could just as easily apply to US government bird flu researchers.

A lot of hullabaloo has been given to the latest press statement from the National Institute of Allergy and Infectious Disease, or NIAID.  NIAID is part of the Department of Health and Human Services, or HHS.  So is the Centers for Disease Control and prevention, or CDC for short.

Anyway, NIAID researchers believe that while tinkering with both the H5N1 and H1N1 (1918 killer) viruses, they have found the amino acid changes necessary to allow H5N1 to adhere to the epithelial cells in the human respiratory tract.  Or more simply put, they have found the Hemagglutinin "velcro" that would stick to human throats and nasal passages. I quote directly from the Reuters story:

To better try and understand the threat, researchers have studied various strains of H5N1 and compared them to the worst known flu virus ever — the H1N1 virus that killed anywhere between 50 million and 100 million people in 1918 and 1919.

They found a mutation that makes one strain of the H1N1 virus more easily infect birds, and another one prefer humans. It lies in the part of the virus that attaches to cells in the respiratory tract. (Bold type mine.)

They then made the same alteration in an H5N1 virus, and vaccinated mice with some of this genetically engineered H5N1 DNA. They found an antibody that could neutralize both types of H5N1 — H5N1 adapted to birds, and an engineered form that would in theory prefer humans.

“It delivers a powerful blow against this virus and really hits it where it lives,” Nabel said.

If a vaccine could be designed to protect people against viruses with this mutation, it might be used before a pandemic even started, Nabel said.

A monoclonal antibody could be used to treat people who were already infected, he added.

But wait, I thought these changes would be much more difficult to produce in a lab!  I quote directly from a CDC press release of July 31, 2006:

Researchers then swapped genes from a 1997 H5N1 avian flu virus with genes from an H3N2 virus, in a process called reassortment. When tested using the ferret model, these “hybrid” viruses (viruses that contained both avian H5N1 and human H3N2 influenza virus genes) did not pass easily between ferrets and, in fact, caused less severe disease than the original H5N1 virus. The reassortment work was designed to mirror the phenomenon that occurs in nature when two flu viruses combine to form a new virus, a process that led to the 1957 and 1968 pandemics. It is still unknown whether the H5N1 virus could reassort with a human influenza virus in nature.

In a final study, CDC researchers passed a hybrid virus through a series of ferrets to see if the virus would accumulate genetic changes necessary to transmit more easily. The researchers found the process introduced only one genetic change in the virus but didn't enhance its transmissibility.

Although the findings apply only to the specific viruses used in the study, the research suggests that significant genetic changes in the H5N1 virus would likely be needed to create a strain that could cause a pandemic (bold type mine). Future CDC studies will examine whether combining genes from H3N2 strains with more recent H5N1 strains makes the new virus more easily transmissible.

So you have one US government agency claiming they have isolated the amino acid changes in the hemagglutinin protein, while barely a year ago a second US government agency said the changes would be considerably harder to find and create. 

Perhaps the answer lies in the very H5N1 samples used in these two experiments.  CDC was, by its own admission, using the original 1997 killer strain of H5N1.  The NIAID researchers were using "various types" of H5N1, implying several clades, or subtypes of H5N1.  We can only speculate that the well-known Qinghai Clade 2.2 substrain was among them.  Perhaps that key difference is what made the NIAID experiment apparently successful, while the CDC experiment failed to produce a pandemic strain. 

So one the one hand you have NIAID saying that only one change in HA causes a profound affinity for human respiratory cells, while CDC is saying significant changes must occur before the change takes place.  But on the other hand, ferrets are supposed to be much better predictors of human response than mice, so... Harry?  Harry?

Of course, all this laboratory tinkering with primal forces of nature should also make one (justifiably) uneasy.  Witness the recent "DOH!" with our friends the British.  Within the past few days it has been disclosed that one single, solitary lab goof is apparently responsible for the accidental re-release of foot and mouth disease in the UK.  And now, to top things off, an employee of the facility has contracted Legionnaire's Disease.  

I quote from the AP story:

Britain's health and safety agency says there was a "strong probability" the outbreak originated at the Pirbright laboratory southwest of London and was spread by human movement. The laboratory houses both a government Institute for Animal Health research center and vaccine-maker Merial Animal Health.

Lab accidents have resulted in human cases of everything from meningitis to Ebola, but are rare and most are self-contained. Still, diseases that can kill humans have made it out of labs.

"With the amount of virus there is in laboratories around the world, I'm surprised that this kind of thing doesn't happen more often," said Dr. Juan Lubroth, head of infectious diseases at the Food and Agriculture Organization.  "This would not be the first time that we've had an event linked to a virus escaping from a lab," said Dr. Bernard Vallat, director-general of the World Organization for Animal Health. He noted that Britain's rapid response should ensure the outbreak is properly contained.

The World Organization for Animal Health says foot-and-mouth warrants the highest containment level possible. Among its recommendations are that sewage be treated to ensure infectious material is destroyed and that staff shower and change clothes before leaving the lab. Experts also recommend that labs working with the virus be isolated from animals that could be infected.

Concerns about biosafety were triggered after three laboratory-related outbreaks of Severe Acute Respiratory Syndrome in Singapore, Taiwan and China in 2003 and 2004. In Singapore and Taiwan, lab workers inadvertently infected themselves. That was also the case in China, where the infection spread from two lab workers to seven family members and contacts outside the lab.

In 2005, scientists worldwide scrambled to avert a possible global flu outbreak by destroying samples of the 1957 flu pandemic virus that were accidentally sent to 5,000 labs in 18 countries. (Bold type mine)

Though WHO says many laboratory practices have improved since the SARS accidents, much remains to be done.

"We can try to mitigate the risk, but zero risk is probably one of things we can never achieve," said Dr. Nicoletta Previsani, project leader of WHO's global biosafety and biosecurity program.

"It's like when you work in your own kitchen preparing dinner," Previsani said. "You do your best, but sometimes you still cut yourself with a knife."

And now, let us turn to the Overview: International Conference on Biosafety and Biorisks.
I quote from the report on the 2005 Conference: