Posts Tagged ‘Virology’

The 1918 flu virus and its descendants: Part 2 Rediscovering the culprit

Sunday, May 13th, 2012

many other major pandemics were associated with rodents, but not the 1918 flu

I re-read my last post a day after writing it and amended the first line, since I found it misleading. It was the worst flu pandemic ever, but I knew that smallpox, the Black Plague, AIDS, malaria and perhaps even typhus each have caused nearly as many or even more deaths over a period of years. I eventually found a rather strange, non-medical website with the "7 Worst Killer Plagues in history," and confirmed my belief that no other bacteria or virus had wreaked as much havoc in brief span of time as the 1918-1919 H1N1 influenza virus.

I wanted to find out what happened to that highly pathogenic organism and, after searching the web, realized the PBS article on the "Spanish flu" was a good place to start. It mentions that the influenza virus was not identified until 1933 and that the actual genetic identity of the particular strain involved in that pandemic (as opposed to the basic type...H1N1) was not identified for many years. The influenza virus responsible for the 1918-1919 pandemic has had many descendants, none as deadly as their ancestor.

In 1950, Johan V Hultin, a graduate student starting his doctoral studies in microbiology, got a clue from a visiting professor who suggested hunting for the virus in bodies buried 32 years prior in the permafrost of the Arctic. Hultin and his faculty advisor traveled to Alaska where flu among the Inuits had been especially deadly with 50 to 100% death rates in five villages.

early days in the Far North

Gold miners, under contract with the Territorial government, had served as grave diggers in 1918-1919 and tissue samples were recovered from four bodies exhumed in 1951. Pathology slides fit with viral lung damage and, in some cases, secondary bacterial pneumonia. But tissue cultures from the samples did not cause disease in ferrets and no influenza virus was recovered.

It wasn't until 1995 that science had advanced enough to for researchers to start the work necessary to identify the virus's unique features. Jeffrey Taubenberger, a molecular pathologist then working at the Armed Forces Institute of Pathology (AFIP), began a ten-plus-year-long project starting with autopsy tissues from the time of the pandemic that had been preserved in the National Tissue Repository. His project was stimulated by a paper published in the journal Science in February, 1995, in which preserved tissue samples from the famous British scientist John Dalton (often called the father of modern atomic theory) were examined. Dalton was color-blind and had donated his eyes at his death in 1844 to determine the cause of the defect; his DNA was studied 150 years later and the resultant publication gave Taubenberger the impetus to do the same with the flu virus.

Hultin read the first paper from Taubenberger's group, wrote to him and eventually went back to Alaska to exhume more flu victims. One was an obese woman whose lungs had the findings of acute viral infection. Samples of these permafrost-preserved tissue had RNA incredibly similar to those obtained from the AFIP National Tissue repository.

And so began an amazing chapter in the history of virology.

Mutating the deadly H5N1 flu virus

Saturday, May 5th, 2012

This ferret is healthy

There's been a recent controversy as to whether potentially dangerous medical information should be made available to the public. Now it's happened and I'm somewhat less concerned than I was a few weeks ago. The online version of Nature just published the work of the University of Wisconsin group on making the Highly Pathogenic Avian Influenza (HPAI) type A H5N1 virus transmissible from mammal to mammal, in this case ferrets.

This is potentially a terrible disease; it's killed 355 of the 602 humans (~59%) known to have contracted the HPAI A(H5N1) virus to date. None of those cases involved human to human spread of the flu bug involved. But that's roughly 600 times as lethal as an "ordinary" flu pandemic and more than 20 times as deadly as the 1918 flu.

So why am I less worried than I was?

When I read the article in Nature in detail (and it's tough slogging even for a physician), I realized that the virus, in the process of making it capable of airborne transmission, had also been made less virulent. None of the ferrets used as research subjects died of the disease . The new virus was also found to be preventable by a vaccine and treatable with one of the existing anti-flu medications.

The other thing I quickly understood is this is not a process that the average man (or woman) on the street or even the vast majority of scientists and/or physicians could duplicate. It involved an enormously complex set of laboratory procedures, many of which would demand long-term expertise and experience in the field. Theoretically a virology lab could be influenced by links to a terrorist group or have their own "ultra-green" agenda; neither possibility sounds at all likely to me.

The other paper, detailing the work done on HPAI A(H5N1) in Rotterdam, is yet to be published. That one has me more concerned, but I've just read a paper "Dangerous for ferrets: lethal for humans?" that carefully explores the question involved.

The authors reminded us that a previous paper had discussed the recreation of the so-called Spanish flu virus that killed 50 million worldwide in 1918. I'll write about that in detail some other time, but when that publication appeared, its authors were hailed as heroes, not as dolts.

The work of Ron Fouchier, a senior figure at the Erasmus Medical Center in Holland took the virology world by storm. He first announced his group's alteration of H5N1 at an international meeting in Malta in September, 2011. Initially his variant of the flu virus was thought to be much more deadly to ferrets than the UW bug. A May 3, 2012 paper in Time Healthland discusses the infighting among scientists that followed, but notes that Fouchier's paper should be out in the magazine Science in the near future.

Apparently Fouchier's mutated virus also turned out to be less of a ferret-killer than was initially thought.

There's the normal flu season and the other kind

But that's not the major issue here. Most of those working in the virology field feel a natural mutation of H5N1 or H1N1 or other flu strains is more to be feared than anything produced in a lab. Yet the relatively benign 1977 H1N1 flu pandemic, so-called Russian flu, may have escaped from deep freeze in a lab.

Every year has its flu season; some are much worse than others.