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Recreating the Spanish flu - articles 2003/2005

Sat, 15 Oct 2005 13:15:06 +0100

 

 

 

The Sunshine Project

Briefing Paper - 9 October 2003

http://www.sunshine-project.org

 

 

This briefing is extracted from: Emerging Technologies: Genetic

Engineering and Biological Weapons, Sunshine Project Backgrounder #12,

October 2003 (forthcoming)

Recreating the Spanish flu?

 

Influenza as a bioweapon does not sound like a particularly grave

threat. Annual outbreaks kill many people, particularly the elderly;

but a case of the flu is generally percieved as an uncomfortable

nuisance rather than a grave threat. But flu viruses can be

devastating. In 1918 and 1919, the so-called " Spanish flu " killed an

estimated 20-40 million people worldwide and, since then, the highly

changeable flu virus has resurfaced in a variety of particularly

virulent forms.

 

The strain of influenza virus that caused the 1918 global epidemic

( " pandemic " ) was exceptionally aggressive. It showed a high capacity

to cause severe disease and a propensity to kill fit young adults

rather than the elderly. The mortality rate among the infected was

over 2.5%, as compared to less than 0.1% in other influenza epidemics

(Taubenberger et al. 1997). This high mortality rate, especially

amongst the younger, lowered the average life expectancy in the USA by

almost 10 years (Tumpey et al. 2002). Creation of this particularly

dangerous influenza strain, as it is currently pursued by a US

research team, may thus pose a serious biowarfare threat.

 

A recent commentary in the Journal of the Royal Society of Medicine

(Madjid et al. 2003) noted that influenza is readily transmissible by

aerosol and that a small number of viruses can cause a full-blown

infection. The authors continued: " the possibility for genetic

engineering and aerosol transmission [of influenza] suggests an

enormous potential for bioterrorism " The possible hostile abuse of

influenza virus is seen as a very real threat by public health

officials in the USA. Just two weeks ago, $15 million was granted by

the US National Institutes of Health to Stanford University to study

how to guard against the flu virus " if it were to be unleashed as an

agent of bioterrorism " .[1]

 

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.[2] 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 " [3] explained Taubenberger 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[4], 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.[5] 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).[6]

 

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[7]. 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.

 

The scientists were aware of the dangers of their creation. The

experiments were conducted under high biosafety conditions at a

laboratory of the US Department of Agriculture in Athens, Georgia.

Possible hostile use of their work was an issue considered by the

scientists: " the available molecular techniques could be used for the

purpose of bioterrorism " (Tumpey et al. 2002:13849).

 

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. " [8] 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 or malaria.

 

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.

 

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.

References

 

Basler CF, Reid AH, Dybing JK, Janczewski TA, Fanning TG, Zheng HY,

Salvatore M, Perdue ML, Swayne DE, García-Sastre A, Palese P,

Taubenberger JK (2001) Sequence of the 1918 pandemic influenza virus

nonstructural gene (NS) segment and characterization of recombinant

viruses bearing the 1918 NS genes. PNAS 98:2746-2751

 

Madjid M, Lillibridge S, Mirhaji P, Casscells W (2003) Influenza as a

bioweapon. J Roy Soc Med 96:345-346

 

Reid AH, Janczewski TA, Raina M. Lourens RM, Elliot AJ, Rod S, CL

Berry, JS Oxford, JK Taubenberger (2003) 1918 Influenza pandemic

caused by highly conserved viruses with two receptor-binding variants.

Emerg Infect Dis [serial online] October 2003, available from:

http://www.cdc.gov/ncidod/EID/vol9no10/02-0789.htm

 

Reid A, Fanning TG, Janczewski TA, McCall S, Taubenberger JK (2002)

Characterization of the 1918 " Spanish " Influenza Virus Matrix Gene

Segment. J Virol 76:10717-10723

 

Taubenberger JK, Reid AH, Krafft AE, Bijwaard KE, Fanning TG (1997)

Initial genetic characterization of the 1918 `Spanish' influenza

virus. Science 275:1793-1796

 

Tumpey TM, Garcia-Sastre A, Mikulasova A, Taubenberger JK, Swayne DE,

Palese P, Basler CF (2002) Existing antivirals are effective against

influenza viruses with genes from the 1918 pandemic virus. PNAS

99:13849-13854

 

[1] Stanford University News Release 17 September 2003, online at

http://mednews.stanford.edu/news_releases_html/2003/septrelease/bioterror%20flu.\

htm

 

[2] Spanish flu keeps its secrets. Nature science update at

www.nature.com/nsu/990304/990304-5.html

 

[3] Profile: Jeffery Taubenberger at

www.microbeworld.org/htm/aboutmicro/what_m_do/profiles/taubenberger.htm

 

[4] AFIP scientists discover clues to 1918 Spanish flu,

www.dcmilitary.com/army/stripe/archives/mar28/str_flu032897.html

 

[5] The so called " nonstructural " gene (NS)

 

[6] 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.

 

[7] 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)

 

[8] 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

 

 

 

http://www.sunshine-project.org/

 

The Sunshine Project

News Release

5 October 2005.

 

Disease by Design: 1918 " Spanish " Flu Resurrection Creates Major

Safety and Security Risks

 

The resurrection of 1918 influenza has plunged the world closer to a

flu pandemic and to a biodefense race scarcely separable from an

offensive one, according to the Sunshine Project, a biological weapons

watchdog.

 

" There was no compelling reason to recreate 1918 flu and plenty of

good reasons not to. Instead of a dead bug, now there are live 1918

flu types in several places, with more such strains sure to come in

more places, " says Sunshine Project Director Edward Hammond, " The US

government has done a great misdeed by endorsing and encouraging the

deliberate creation of extremely dangerous new viruses. The 1918

experiments will be replicated and adapted, and the ability to perform

them will proliferate, meaning that the possibility of man-made

disaster, either accidental or deliberate, has risen for the entire

world. "

 

The 1918 experiments are part of the US biodefense program and are of

no practical value in responding to outbreaks of " bird flu " (H5N1).

The 1918 virus is a different type (H1N1) of influenza than " bird

flu " . 1918 flu is more than eighty five years old and no longer exists

in nature, posing no natural threat. While it is reasonable to

determine the genetic sequence of 1918 and other extinct influenza

strains, there is no valid reason to recreate the virulent virus, as

the risks far outweigh the benefits.

 

But the most significant story isn't Tumpey, Taubenberger, and

colleagues. It is the Centers for Disease Control's (CDC) attitude

about the experiments and its implications. " The biggest news about

resurrecting 1918 flu is the US government's enthusiastic embrace of

designer disease and the impact that it will have on our future. " says

Hammond, " By encouraging genetic riffs on influenza and other viruses

with the explicit intent of building more dangerous pathogens, CDC is

fueling the gathering dangers of competition to discover the worst

possibilities of biotechnology applied to bioweapons agents. Some

might do it just to keep up with the Americans, resulting in a further

blurring of defense and offense and heightening the biological

mistrust evident in US foreign policy. "

 

In addition to the potentially broad damage to international security

and cooperation in the biological sciences if novel diseases continue

to be created, the 1918 experiments heighten the chance that a flu lab

will be the source of the next pandemic.

 

CDC says that it plans to keep its vials of 1918 flu under close guard

in one place. But that's a red herring according to the Sunshine

Project. Influenza with as many as five 1918 flu genes, and which are

potentially pandemic, have already been handled at labs in at least

four places other than CDC, including labs in Athens, GA, Winnipeg, MB

(Canada), Seattle, WA, and Madison, WI. With the exception of the

Canadian lab, none of these facilities has maximum (BSL-4) biological

containment, and it is a virtual certainty that more labs will begin

1918 flu work now.

 

In fact, the only possible source of a new 1918 influenza outbreak is

a laboratory. The situation of the 1918 flu is not dissimilar to SARS,

whose natural transmission is believed to have been halted. The

experience with SARS accidents is chilling: It has escaped three

different labs to date. A 1918 influenza escape would be very likely

to take a higher human toll. The US biodefense program has also had a

number of lab accidents since 2002, including mishandling of anthrax

and plague and laboratory-acquired infections of tularemia. In Russia,

a researcher contracted ebola and died last year.

 

Importantly, human error and equipment failures aren't the only ways

for a disease agent to escape a lab - something vividly illustrated by

the anthrax letters in the US four years ago. Unlike anthrax, however,

1918 influenza would transmit from human to human.

 

" We are no safer from a pandemic today than yesterday. In fact, we're

in greater danger, not only from influenza; but from the failure of

the US to come to grips with and address the threats posed by the

research it sponsors, in terms of legislation, ethics, and

self-restraint. " concludes Hammond.

 

-end-

 

forwarded by

Zeus Information Service

Alternative Views on Health

www.zeusinfoservice.com

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