Saturday :: Jul 17, 2004

Don't Bug Me, Man! You're Making Me Ill!


by pessimist

They are trying to kill us. Really.

Lab Bioresearch Error May Cause Next Pandemic

It's back from the dead. It packs a lethal punch. It's the 1918 "Spanish" Flu virus. (The 1918 influenza strain is popularly called "Spanish" influenza, based on incorrect suspicions about its origin at the time of the outbreak. In fact, to this day, there is no scientific consensus on the origin of the strain.) In its heyday decades ago, 1918 influenza killed ten, perhaps twenty million people worldwide.

The 1918 flu was recently brought back to life by scientists from the US Departments of Defense and Agriculture, and private institutions including the Mt. Sinai School of Medicine in New York. Digging through archives of medical samples and, literally, digging up the dead, the team's work resulted in the re-emergence - in the lab - of one of the most dreaded diseases in human history.

As if trying to create the Four Horsemen of the Apocalypse in order to bring on the Rapture (which my Bible reading indicates is not up to mankind to initiate), the (mis)Administration of George Warmonger Bush has done much that could be interpreted by the weak mind as being the signs of the end times so revered by Christian Fundamentalism. He's certainly brought War and Death, and now seems to be working on a third - Pestilence.

This influenza was so bad, it's the only time in our nation's history that our population actually declined! Why the hell do they want to mess around with that now? Have not the incredibly dangerous qualities of such a viral strain already been demonstrated by Mother Nature?

Sure - and that's why the research. It is intended to be a weapon - one which can't be defended against in time to prevent huge numbers of deaths. One which an invading army can be immunized against.

Scientists unlock secret of deadly Spanish Flu

Scientists hope to improve their understanding of the 1918 pandemic still further by exhuming the body of a 20-year-old British victim. Phyllis Burn, an Army officer's daughter was buried in a cemetery in Twickenham, south of London, 85 years ago. She was laid to rest in a lead coffin which, if properly sealed, would have been virtually airtight. Scientists hope her internal organs may be sufficiently preserved to allow tissue samples to be taken from her lungs.


Team hopes to solve Spanish flu mystery

A Canadian-led research team hopes a tiny graveyard on a remote Norwegian island may hold the secret to a deadly flu virus that ravaged the globe 80 years ago, killing tens of millions of people. The team will fly to Norway later this month to probe the graves of seven young miners who succumbed to the Spanish flu in the autumn of 1918. The seven Longyearbyen miners were ages 19-27. The research team will chart the graves and use special radar to determine whether the bodies were buried deep enough to have remained frozen for the past eight decades. If the bodies have stayed frozen, the team will return next year to excavate the site and take core samples of frozen tissue from the bodies. The researchers hope the bodies -- buried in the small mining town of Longyearbyen, north of the Arctic Circle -- still hold traces of the lethal virus and can provide clues to fighting future epidemics. Because nobody kept a sample of the virus in 1918, the researchers hope to unlock its genetic code from tissue samples and compile information to help prevent similar outbreaks in the future. Researchers hope to determine why young, healthy people fell to the Spanish flu when they usually are able to easily recover from other strains.


Is Mystery Illness Resurrected 'Spanish Flu'?

From Patricia Doyle, PhD
dr_p_doyle@hotmail.com

I was totally against "digging up" Spanish flu samples. It was too risky and the chance of it emerging (NATURALLY) were slim. Of course, once the virus was resurrected, the chance of lab accidental release or intentional was then a factor. The risk far outweighed the benefit. It is quite possible that China had an expedition to exhume tissue samples containing live H1N1 flu virus. The US and UK expedition was quite publicized and it is not unreasonable to think that China might have opted to get some samples as well.


Finding Virus Samples for Study

In 1951, scientists from the University of Iowa exhumed bodies of victims of the 1918 flu that had been buried in permafrost in Teller Mission, an Inuit fishing village on the Seward Peninsula of Alaska. This village, now called Brevig Mission, suffered extremely high mortality rates during the influenza pandemic in November 1918. According to available records, influenza spread through the village in about 5 days and killed 72 people, representing about 85% of the adult population.

During the 1951 expedition, samples of lung, brain, and other organs were taken for histologic analyses and viral culture. All attempts to culture live influenza virus from these specimens were unsuccessful. Molecular genetic analyses of the samples were impossible at that time--indeed, the double-stranded structure of DNA, with its implications for molecular genetics, was not determined until 1953.

In 1995, my laboratory initiated a project to characterize the 1918 influenza virus genetically using archival formalin-fixed, paraffin-embedded autopsy tissues of 1918 flu victims stored in the National Tissue Repository of the Armed Forces Institute of Pathology (AFIP). A search of the archives revealed over 70 autopsy cases of U.S. soldiers who died of influenza pneumonia in the fall of 1918. We used techniques to isolate RNA that had been optimized for fixed tissue specimens based on previous studies.

In total, 78 autopsy cases of victims of the lethal fall wave of the 1918 pandemic were examined for this study, and 74 of these consisted of fixed tissue samples. The majority of these individuals died of secondary bacterial pneumonia. Because they often had clinical courses longer than one week, it was extremely unlikely that any of the tissue samples from these cases would still retain influenza RNA.

However, a subset of individuals died within one week, with very unusual and characteristic lung pathology including massive pulmonary edema or hemorrhage. These patients literally drowned in their own serum or blood, often in as little as 48 hours. While these pathologic changes have been seen in other influenza outbreaks (including during the 1957 ``Asian'' flu outbreak), its prominence in 1918 is one of the cardinal features of the Spanish flu. We then concentrated our efforts on specimens from this subset of patients.

Pathologist Johan V. Hultin submitted a third case to the AFIP in 1997. Hultin was a team member of the 1951 University of Iowa project. After reading about our results with fixed tissue specimens, he contacted us about obtaining new frozen lung biopsies of 1918 flu victims from the same mass grave sampled in 1951. He obtained permission of the Brevig Mission City Council and obtained in situ frozen lung biopsies of four victims of the 1918 flu. These samples were placed in fixatives for histologic analysis and RNA isolation. No attempt to culture virus was made.

Lung tissue samples of one of these cases, an Inuit female nicknamed Lucy by Hultin, was positive for influenza RNA. Histologically, sections of her lung show evidence of massive pulmonary hemorrhage, consistent with a rapid clinical course. Unfortunately, influenza RNA fragments in this case are no longer than those obtained from the fixed cases.


Recreating the Spanish flu?

US scientists led by a Pentagon pathologist recently began to genetically reconstruct this specifically dangerous 1918 influenza strain. In one experiment a partially reconstructed 1918 virus killed mice, while virus constructs with genes from a contemporary flu virus had hardly any effect.

Attempts to recover the Spanish flu virus date to the 1950s, when scientists unsuccessfully tried to revive the virus from victims buried in the permafrost of Alaska. [Spanish flu keeps its secrets]

In the mid 1990s, Dr Jeffrey Taubenberger from the US Armed Forces Institute of Pathology started to screen preserved tissue samples from 1918 influenza victims. It appears that this work was not triggered by a search for flu treatments, or the search for a new biowarfare agent, but by a rather simple motivation: Taubenberger and his team were just able to do it. In previous experiments they had developed a new technique to analyse DNA in old, preserved tissues and for now looking for new applications: "The 1918 flu was by far and away the most interesting thing we could think of" [Profile: Jeffery Taubenberger] explained Taubenberger [as] the reason why he started to unravel the secrets of one of most deadliest viruses known to humankind.

A sample of lung tissue from a 21-year-old soldier who died in 1918 at Fort Jackson in South Carolina [AFIP scientists discover clues to 1918 Spanish flu], yielded what the Army researchers were looking for: intact pieces of viral RNA that could be analysed and sequenced. In a first publication in 1997, nine short fragments of Spanish flu viral RNA were revealed (Taubenberger et al. 1997). Due to the rough tissue preparation procedure in 1918, no living virus or complete viral RNA sequences were recovered.

Genetic techniques helped to isolate more Spanish flu RNA from a variety of sources. By 2002, four of the eight viral RNA segments had been completely sequenced, including the two segments that are considered to be of greatest importance for the virulence of the virus: the genes for hemagglutinin (HA) and neuraminidase (NA). In the forthcoming issue of the scientific journal Emerging Infectious Diseases, another article on the Spanish flu DNA sequence will be published (Reid et al. 2003).

The project did not stop at sequencing the genome of the deadly 1918 strain. The Armed Forces Institute of Pathology teamed up with a microbiologist from the Mount Sinai School of Medicine in New York. Together, they started to reconstruct the Spanish flu. In a first attempt, they combined gene fragments from a standard laboratory influenza strain with one 1918 gene.[The so called "nonstructural" gene (NS)] They infected mice with this chimera, and it turned out that the 1918 gene made the virus less dangerous for mice (Basler et al. 2001).[It should be noted that for this experiments, a standard influenza strain was used that was specifically adapted to mice and that was lethal to mice. The scientists reasoned that the 1918 gene probably weakened the lethality for the mice as it stemmed from a human-adapted strain.]

In a second experiment, published in October 2002 (Tumpey et al. 2002), the scientists were successful in creating a virus with two 1918 genes. This virus was much more deadly to mice than other constructs containing genes from contemporary influenza virus [This time, the 1918 genes for hemagglutinin (HA), neuraminidase (NA) and matrix (M) were used, single and in combination. Only the combination of the 1918 HA and NA genes caused a dramatic increase in lethality if compared to constructs containing genes from a more recent human influenza virus. The scientists concluded: "These data suggest that the 1918 HA and NA genes might possess intrinsic high-virulence properties." (Tumpey et al. 2002:13853)]. This experiment is only one step away from taking the 1918 demon entirely out of the bottle and bringing the Spanish flu back to life.

There is no sound scientific reason to conduct these experiments. The most recent experiments (Tumpey et al. 2002) allegedly seeked to test the efficacy of existing antiviral drugs on the 1918 construct – but there is little need for antiviral drugs against the 1918 strain if the 1918 strain would not have been sequenced and recreated in the first place.

It is true that biodefense research – and any kind of civilian medical research – is always a race with its counterpart, the evolution of naturally occuring infectious agents or the development of biowarfare agents. But in this race it should be avoided to create the threats that are allegedly the motivation for the research. A vicious circle is created: "The technologies are in place with reverse genetics to generate any influenza virus we wish ... studies are envisaged using genes of the 1918 Spanish Influenza virus." [Letter (4 February 2003) from Robert G. Webster, Professor of Virology at St. Jude Children's Research Hospital to Stanley Lemon, Dean, School of Medicine, University of Texas Medical Branch (UTMB) at Galveston, in support of the UTMB application to contruct a National Biocontainment Laboratory. Released to the Sunshine Project under the Texas Public Information Act] These arguments were recently brought forward to justify another maximum biosafety laboratory for biological defense work in Texas.

Without Taubenberger’s pioneering work, the money for the lab experiments might have been saved and better invested in combatting naturally occuring diseases such as tuberculosis, malaria, or HIV.

Other papers argued that the experiments may help to elucidate the mechanisms of influenza evolution and virulence (Taubenberger et al. 1997, Basler et al. 2001), but this argument is also deeply flawed. Since 1918, a many different influenza viruses with different virulence and pathogenicity properties have been isolated and characterised by researchers around the world - a more than abundant source for generations of scientists to study influenza evolution and virulence. A resuscitation of the Spanish flu is neither necessary nor warranted from a public health point of view.

Pride Goeth Before The Fall

There may be many reasons for the individual scientists to work on this project, not least the scientific prestige - the "Spanish flu" subject matter practically guaranteed a series of publications in prestigious journals. From an arms control perspective it appears to be particularly sensitive if a military research institution embarks on a project that aims at constructing more dangerous pathogens - if Jeffery Taubenberger worked in a Chinese, Russian or Iranian laboratory, his work might well be seen as the "smoking gun" of a biowarfare program.


UW Bends Safety In 1918 Flu Experiments
Lab Bioresearch Error May Cause Next Pandemic

From Patricia Doyle, PhD
dr_p_doyle@hotmail.com
ra.microslu.washington.edu
7-14-4

Summary: As more laboratories begin to handle genetically-recreated 1918 "Spanish" Flu and similar flu strains, the chances that a lab will be the source of the next global influenza pandemic increase. The skyrocketing biodefense budget, now exceeding that of the Manhattan Project (adjusted for inflation), is rapidly increasing research on biological weapons agents, including risky genetic engineering projects. Despite this, the Bush administration maintains that comprehensive laboratory safety and disclosure law is unnecessary, because an alleged "culture of responsibility" among institutional biosafety committees will protect Americans, and the world, from its biodefense research. But at the University of Washington in Seattle, whose scientists are eager to handle 1918 Spanish Flu, the IBC's judgment is unsound. It has approved experiments by summarily changing the containment level of a planned lab, using inappropriate safety benchmarks, and by unilaterally lowering the safety threshold required for work with the potentially pandemic virus.

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The 1918 flu was recreated at a lab at the University of Georgia. Now, flu strains with 1918 genes are cropping up in other labs across the country. There are reasons for scientists to study why the 1918 flu was so devastating. A similarly virulent strain could reappear naturally. But a need to understand why 1918 flu was so devastating doesn't necessarily justify recreating and widely distributing a very dangerous - and otherwise eradicated - bug.

Because influenza spreads so easily (as the "new" 1918 strain and its lab-created genetic cousins are sent to more facilities), the risk that the next major influenza pandemic will be man-made is on the rise. It wouldn't be the first time that an influenza lab accident made the whole world ill. (It is an unpublished; but open secret among influenza researchers that a global pandemic of H1N1-type influenza that began in 1977 was, in all likelihood, the result of an accidental release from a lab in China. Public references to the origin of this outbreak occasionally surface. See, for example, ProMedMail, 1 June 2004.) And, of course, scientists in other countries may repeat the US 1918 experiments, resulting in even wider proliferation of very dangerous man-made bugs. So then, it is logically the case that responsible labs that are handling 1918 influenza are taking extraordinary precautions through their institutional biosafety committees (IBCs), which are charged with ensuring safety of such experiments.

Ideally, that is.

But things got off to a bad start with the 1918 influenza. When it was recreated, neither the US Department of Agriculture nor the University of Georgia (the institutions in charge of the Georgia lab) bothered to have an IBC review the experiments. (USDA Agricultural Research Service reply, dated 2 October 2003, to Sunshine Project FOIA of 11 August 2003, for minutes of the IBC meeting that reviewed 1918 influenza experiments. Personal communication with Daryl Rowe, Institutional Biosafety Officer, University of Georgia, September 2003.)

Still, according to science policymakers, USDA and Georgia's failure should be an anomaly. That is because while the National Academy of Sciences and the Bush administration have rejected regulation of labs, they say that the "culture of responsibility" of institutional biosafety committees will ensure safety in the brave new world of aggressive biodefense research.

But the rhetoric isn't matched by the realities of the IBC system. USDA and the University of Georgia aren't the only problems. In fact, they aren't even the only problem when it comes to 1918 influenza.

In Seattle, University of Washington (UW) researchers are gearing up for some of the most ambitious experiments yet undertaken with 1918 influenza. UW will work with the previously recreated 1918 flu and make more types by inserting the critical 1918 virulence-related genes into a similar (H1N1) but less dangerous type of flu that was isolated in Texas in 1991. UW researchers' plans include culturing 1918 viruses, infecting animal cell lines with them, isolating samples after such 'passages' and, in the course of research, shuffle through the lab with various biological materials and equipment containing live 1918 flu types.

The objective is to develop and research a non-human primate (Pigtail macaque) model for 1918 influenza infection. In other words, the experiments will culminate by UW spraying lab monkeys with genetically engineered 1918/Texas flu and recording the results. The macaques might rather be home in Southeast Asia; but the hope is that using them as models for human infection with 1918 flu will provide useful information for managing flu outbreaks, either natural or deliberate.

But the University of Washington doesn't have an appropriately facility for the studies and its IBC isn't at all clear or vigorous in implementing necessary safety protocols.

The UW IBC's approval of Spanish flu experiments is, however, critical for the projects to receive federal funding. So, in August 2003, the UW IBC took up the matter. The first problem it encountered was that the animal biosafety level three (ABSL-3) facility where the experiments were to take place hasn't been built. Secondly, USDA, which was providing the 1918 influenza, had classified it as requiring BSL-3ag containment.(How USDA and/or Georgia determined BSL-3ag containment, which is stated in the UW IBC minutes and NIH grant abstracts, is unclear. As indicated in note 3, under FOIA, USDA asserts that no IBC ever reviewed the project to re-create 1918 influenza.) BSL-3ag is a more stringent standard than that of existing UW labs and the planned ABSL-3 lab. BSL-3ag is just one step short of maximum containment BSL-4, the level that a cautious institution might have assigned the 1918 constructs in the first place. (Neither USDA nor Georgia, however, have a BSL-4 lab.)

Apparently unwilling to hold its researchers back over biosafety issues, and despite the lack of adequate facilities, the UW IBC approved 1918 flu projects. It has allowed some activities to go forward in an existing (non-animal) BSL-3 facility, despite USDA's BSL-3ag designation of the agent. Remarkably, the UW IBC also decided, on the spot, to change the biosafety level of the new UW lab. The IBC decided that the new lab, previously not intended to be BSL-3ag, would meet the more stringent designation "in principle". This dubious endorsement enabled grant applications to move forward and for UW researchers to proceed to acquire the 1918 flu from USDA, with the "in principle" UW BSL-3ag lab.

After "resolving" the problem of not having appropriate containment, the UW IBC then considered the operating procedures to be followed in the existing BSL-3 lab for 1918 flu experiments. Here, the "culture of responsibility" of the UW IBC again failed.

The benchmark that the UW IBC referred to for 1918 flu safety were procedures used to handle human immunodeficiency virus (HIV). But the virus that causes AIDS is relatively difficult to transmit, especially by aerosol, the main cause for concern with influenza. Moreover, the risk to the community posed by a lab-acquired HIV infection is trivial in comparison to the threat posed to the world by a case of potentially pandemic influenza.

The UW IBC only considered one of the many opportunities for influenza aerosolization in the studies, that if a tray were dropped. In such an event, the UW IBC decided that researchers "will be trained to stop breathing... just as they are taught to do when working with HIV". An independent microbiologist who the Sunshine Project provided a copy of the UW IBC minutes called the UW biosafety protocols in the 1918 project to be "inappropriate" and "risible".

The minutes of the UW IBC also suggest - but don't entirely clarify - that UW researchers, already working at a lower level of containment than that assigned by USDA, may plan to place cultures infected with 1918 influenza in an unshielded centrifuge. Because their spinning energy can rapidly aerosolize liquids, centrifuges are a notorious source of laboratory infections.

UW's irresponsible treatment of biosafety in the 1918 influenza project does not appear to bother the National Institute of Allergy and Infectious Disease (NIAID). NIAID recently funded the project. Its formal start date was the beginning of this month, July 1st, 2004. (NIH Grant 1P01AI058113-01 to the Mt. Sinai School of Medicine includes the UW component for 1918 influenza studies.)
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Other sources:

Minutes of the University of Washington Institutional Biosafety Committee, meetings of 2 December 2002 and 22 August 2003.

Baskin CR et al. Gene Expression Control in Pigtail Macaques Infected with Influenza A/Texas/36/91: A PILOT STUDY. Innate Immune Response and Patterns of Immune Cell Migration in an Uncomplicated Influenza Infection, online poster submission for the Fifth Annual Northwest Gene Expression Conference, to be held at the University of Washington, 25-27 May 2005.

Patricia A. Doyle, PhD

Please visit my "Emerging Diseases" message board.

Zhan le Devlesa tai sastimasa (Go with God and in Good Health)


So there it is - the Bush Holy Roller End Times Corral has Three of the Four Horsemen either actively prancing about or ready to. Can Famine be far behind?

Actually, if the environment continues to be destroyed by BushCo activities, that Horseman may already be in the stable, being groomed to emerge and complete the team.

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pessimist :: 6:26 AM :: Comments (1) :: Digg It!