Emerging Technologies: Genetic Engineering and Biological Weapons

[Guest guest]

The Sunshine ProjectBriefing Paper - 9 October 2003http://www.sunshine-project.org This briefing is extracted from: Emerging Technologies: GeneticEngineering and Biological Weapons, Sunshine Project Backgrounder #12,October 2003 (forthcoming)Recreating the Spanish flu? Influenza as a bioweapon does not sound like a particularly gravethreat. Annual outbreaks kill many people, particularly the elderly;but a case of the flu is generally percieved as an uncomfortablenuisance rather than a grave threat. But flu viruses can bedevastating. In 1918 and 1919, the so-called "Spanish flu" killed anestimated 20-40 million people worldwide and, since then, the highlychangeable flu virus has resurfaced in a variety of particularlyvirulent forms. The strain of influenza virus that caused the 1918 global epidemic("pandemic") was exceptionally aggressive. It showed a high capacityto cause severe disease and a propensity to kill fit young adultsrather than the elderly. The mortality rate among the infected wasover 2.5%, as compared to less than 0.1% in other influenza epidemics(Taubenberger et al. 1997). This high mortality rate, especiallyamongst the younger, lowered the average life expectancy in the USA byalmost 10 years (Tumpey et al. 2002). Creation of this particularlydangerous influenza strain, as it is currently pursued by a USresearch 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 byaerosol and that a small number of viruses can cause a full-blowninfection. The authors continued: "the possibility for geneticengineering and aerosol transmission [of influenza] suggests anenormous potential for bioterrorism" The possible hostile abuse ofinfluenza virus is seen as a very real threat by public healthofficials in the USA. Just two weeks ago, $15 million was granted bythe US National Institutes of Health to Stanford University to studyhow to guard against the flu virus "if it were to be unleashed as anagent of bioterrorism".[1] US scientists led by a Pentagon pathologist recently began togenetically reconstruct this specifically dangerous 1918 influenzastrain. In one experiment a partially reconstructed 1918 virus killedmice, while virus constructs with genes from a contemporary flu virushad hardly any effect. Attempts to recover the Spanish flu virus date to the 1950s, whenscientists unsuccessfully tried to revive the virus from victimsburied in the permafrost of Alaska.[2] In the mid 1990s, Dr JeffreyTaubenberger from the US Armed Forces Institute of Pathology startedto screen preserved tissue samples from 1918 influenza victims. Itappears that this work was not triggered by a search for flutreatments, or the search for a new biowarfare agent, but by a rathersimple motivation: Taubenberger and his team were just able to do it.In previous experiments they had developed a new technique to analyseDNA in old, preserved tissues and for now looking for newapplications: "The 1918 flu was by far and away the most interestingthing we could think of"[3] explained Taubenberger the reason why hestarted to unravel the secrets of one of most deadliest viruses knownto humankind. A sample of lung tissue from a 21-year-old soldier who died in 1918 atFort Jackson in South Carolina[4], yielded what the Army researcherswere looking for: intact pieces of viral RNA that could be analysedand sequenced. In a first publication in 1997, nine short fragments ofSpanish flu viral RNA were revealed (Taubenberger et al. 1997). Due tothe rough tissue preparation procedure in 1918, no living virus orcomplete viral RNA sequences were recovered. Genetic techniques helped to isolate more Spanish flu RNA from avariety of sources. By 2002, four of the eight viral RNA segments hadbeen completely sequenced, including the two segments that areconsidered to be of greatest importance for the virulence of thevirus: the genes for hemagglutinin (HA) and neuraminidase (NA). In theforthcoming issue of the scientific journal Emerging InfectiousDiseases, another article on the Spanish flu DNA sequence will bepublished (Reid et al. 2003). The project did not stop at sequencing the genome of the deadly 1918strain. The Armed Forces Institute of Pathology teamed up with amicrobiologist from the Mount Sinai School of Medicine in New York.Together, they started to reconstruct the Spanish flu. In a firstattempt, they combined gene fragments from a standard laboratoryinfluenza strain with one 1918 gene.[5] They infected mice with thischimera, and it turned out that the 1918 gene made the virus lessdangerous 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 two1918 genes. This virus was much more deadly to mice than otherconstructs containing genes from contemporary influenza virus[7]. Thisexperiment is only one step away from taking the 1918 demon entirelyout of the bottle and bringing the Spanish flu back to life. The scientists were aware of the dangers of their creation. Theexperiments were conducted under high biosafety conditions at alaboratory of the US Department of Agriculture in Athens, Georgia.Possible hostile use of their work was an issue considered by thescientists:"the available molecular techniques could be used for thepurpose of bioterrorism" (Tumpey et al. 2002:13849). There is no sound scientific reason to conduct these experiments. Themost recent experiments (Tumpey et al. 2002) allegedly seeked to testthe efficacy of existing antiviral drugs on the 1918 construct – butthere is little need for antiviral drugs against the 1918 strain ifthe 1918 strain would not have been sequenced and recreated in thefirst place. It is true that biodefense research – and any kind ofcivilian medical research – is always a race with its counterpart, theevolution of naturally occuring infectious agents or the developmentof biowarfare agents. But in this race it should be avoided to createthe threats that are allegedly the motivation for the research. Avicious circle is created: "The technologies are in place with reversegenetics to generate any influenza virus we wish ... studies areenvisaged using genes of the 1918 Spanish Influenza virus."[8] Thesearguments were recently brought forward to justify another maximumbiosafety laboratory for biological defense work in Texas. WithoutTaubenberger's pioneering work, the money for the lab experimentsmight have been saved and better invested in combatting naturallyoccuring diseases such as tuberculosis or malaria. Other papers argued that the experiments may help to elucidate themechanisms 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 differentvirulence and pathogenicity properties have been isolated andcharacterised by researchers around the world - a more than abundantsource for generations of scientists to study influenza evolution andvirulence. A resuscitation of the Spanish flu is neither necessary norwarranted from a public health point of view. There may be many reasons for the individual scientists to work onthis project, not least the scientific prestige - the"Spanish flu"subject matter practically guaranteed a series of publications inprestigious journals. From an arms control perspective it appears tobe particularly sensitive if a military research institution embarkson a project that aims at constructing more dangerous pathogens - ifJeffery Taubenberger worked in a Chinese, Russian or Iranianlaboratory, his work might well be seen as the "smoking gun" of abiowarfare 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 virusnonstructural gene (NS) segment and characterization of recombinantviruses bearing the 1918 NS genes. PNAS 98:2746-2751 Madjid M, Lillibridge S, Mirhaji P, Casscells W (2003) Influenza as abioweapon. J Roy Soc Med 96:345-346 Reid AH, Janczewski TA, Raina M. Lourens RM, Elliot AJ, Rod S, CLBerry, JS Oxford, JK Taubenberger (2003) 1918 Influenza pandemiccaused 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 GeneSegment. J Virol 76:10717-10723 Taubenberger JK, Reid AH, Krafft AE, Bijwaard KE, Fanning TG (1997)Initial genetic characterization of the 1918 `Spanish' influenzavirus. Science 275:1793-1796 Tumpey TM, Garcia-Sastre A, Mikulasova A, Taubenberger JK, Swayne DE,Palese P, Basler CF (2002) Existing antivirals are effective againstinfluenza viruses with genes from the 1918 pandemic virus. PNAS99:13849-13854 [1] Stanford University News Release 17 September 2003, online athttp://mednews.stanford.edu/news_releases_html/2003/septrelease/bioterror%20flu.htm [2] Spanish flu keeps its secrets. Nature science update atwww.nature.com/nsu/990304/990304-5.html [3] Profile: Jeffery Taubenberger atwww.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 influenzastrain was used that was specifically adapted to mice and that waslethal to mice. The scientists reasoned that the 1918 gene probablyweakened the lethality for the mice as it stemmed from a human-adaptedstrain. [7] This time, the 1918 genes for hemagglutinin (HA), neuraminidase(NA) and matrix (M) were used, single and in combination. Only thecombination of the 1918 HA and NA genes caused a dramatic increase inlethality if compared to constructs containing genes from a morerecent human influenza virus. The scientists concluded: "These datasuggest that the 1918 HA and NA genes might possess intrinsichigh-virulence properties." (Tumpey et al. 2002:13853) [8] Letter (4 February 2003) from Robert G. Webster, Professor ofVirology at St. Jude Children's Research Hospital to Stanley Lemon,Dean, School of Medicine, University of Texas Medical Branch (UTMB) atGalveston, in support of the UTMB application to contruct a NationalBiocontainment Laboratory. Released to the Sunshine Project under theTexas Public Information Act http://www.sunshine-project.org/ The Sunshine ProjectNews Release5 October 2005. Disease by Design: 1918 "Spanish" Flu Resurrection Creates MajorSafety and Security Risks The resurrection of 1918 influenza has plunged the world closer to aflu pandemic and to a biodefense race scarcely separable from anoffensive one, according to the Sunshine Project, a biological weaponswatchdog. "There was no compelling reason to recreate 1918 flu and plenty ofgood reasons not to. Instead of a dead bug, now there are live 1918flu types in several places, with more such strains sure to come inmore places," says Sunshine Project Director Edward Hammond, "The USgovernment has done a great misdeed by endorsing and encouraging thedeliberate creation of extremely dangerous new viruses. The 1918experiments will be replicated and adapted, and the ability to performthem will proliferate, meaning that the possibility of man-madedisaster, either accidental or deliberate, has risen for the entireworld." The 1918 experiments are part of the US biodefense program and are ofno practical value in responding to outbreaks of "bird flu" (H5N1).The 1918 virus is a different type (H1N1) of influenza than "birdflu". 1918 flu is more than eighty five years old and no longer existsin nature, posing no natural threat. While it is reasonable todetermine the genetic sequence of 1918 and other extinct influenzastrains, there is no valid reason to recreate the virulent virus, asthe risks far outweigh the benefits. But the most significant story isn't Tumpey, Taubenberger, andcolleagues. It is the Centers for Disease Control's (CDC) attitudeabout the experiments and its implications. "The biggest news aboutresurrecting 1918 flu is the US government's enthusiastic embrace ofdesigner disease and the impact that it will have on our future." saysHammond, "By encouraging genetic riffs on influenza and other viruseswith the explicit intent of building more dangerous pathogens, CDC isfueling the gathering dangers of competition to discover the worstpossibilities of biotechnology applied to bioweapons agents. Somemight do it just to keep up with the Americans, resulting in a furtherblurring of defense and offense and heightening the biologicalmistrust evident in US foreign policy." In addition to the potentially broad damage to international securityand cooperation in the biological sciences if novel diseases continueto be created, the 1918 experiments heighten the chance that a flu labwill be the source of the next pandemic. CDC says that it plans to keep its vials of 1918 flu under close guardin one place. But that's a red herring according to the SunshineProject. Influenza with as many as five 1918 flu genes, and which arepotentially pandemic, have already been handled at labs in at leastfour places other than CDC, including labs in Athens, GA, Winnipeg, MB(Canada), Seattle, WA, and Madison, WI. With the exception of theCanadian lab, none of these facilities has maximum (BSL-4) biologicalcontainment, and it is a virtual certainty that more labs will begin1918 flu work now. In fact, the only possible source of a new 1918 influenza outbreak isa laboratory. The situation of the 1918 flu is not dissimilar to SARS,whose natural transmission is believed to have been halted. Theexperience with SARS accidents is chilling: It has escaped threedifferent labs to date. A 1918 influenza escape would be very likelyto take a higher human toll. The US biodefense program has also had anumber of lab accidents since 2002, including mishandling of anthraxand 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 waysfor a disease agent to escape a lab - something vividly illustrated bythe 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'rein greater danger, not only from influenza; but from the failure ofthe US to come to grips with and address the threats posed by theresearch it sponsors, in terms of legislation, ethics, andself-restraint." concludes Hammond. -end- forwarded byZeus Information ServiceAlternative Views on Healthwww.zeusinfoservice.com