Bioterrorism and the pharmaceutical industry

& INTERNATIONAL JOURNAL OF PHARMACEUTICAL MEDICINE 2002, 16:63 – 64 63 EDITORIAL ......................................................................................................................... Bioterrorism and the pharmaceutical industry Noel J.C. Snell In August 2000 the International Journal of Pharmaceutical Medicine published a paper entitled ‘Biological weapons and the pharmaceutical industry’ [1]. This detailed review of actual and potential bioweapons highlighted the potential role of the pharmaceutical industry, particularly the concern over the number of countries thought to be using pharmaceutical or biotechnology companies as ‘fronts’ for covert bioweapon research and production. Confirmed cases are the Biopreparet biotechnology company in the former Soviet Union and the Roodeplat Research Laboratories in South Africa that were involved in the development of bioweapons for use in political assassinations. Iraq is also known to have employed statecontrolled biotechnology companies to produce the anthrax bacillus and botulinum toxin, when it was notionally involved in the production of legal biopesticides. The history of biological warfare goes back at least to the Middles Ages, with anecdotal reports that dead horses (and subsequently plague-infected corpses) were catapulted into besieged castles and cities. In the eighteenth century smallpoxinfected blankets were deliberately distributed by British forces to the native American Delaware tribe, with the intent of spreading disease among them. Few deliberate acts of biological warfare have been documented since, although Germany did attempt to spread glanders to horses in the first World War, and the Japanese experimented with operational weapons charged with typhoid, cholera, anthrax and plague against the Soviet Union and China during World War II. Somewhat surprisingly biowarfare research in Germany was vetoed by Hitler [2]. All the major international powers had biological warfare programmes at some stage during the 20th century; it is only recently that Gruinard island, in Scotland, was decontaminated after being used as the testing ground for British anthrax bombs in World War II. The Collison nebulizer (prototype for several nebulizers used for the therapeutic administration of inhaled drugs) was used in wartime experiments with nebulized bacterial suspensions at Porton Down [3]. Bioterrorism (the use of bioweapons by terrorist groups) as opposed to biowarfare (use by nation-states) is a late 20th century development. The sensational terrorist attack on the World Trade Center in New York on 11 September last year was followed in October by reports of pulmonary anthrax in Florida, and subsequently among postal workers in New Jersey and Washington DC. Deliberately contaminated letters were identified as the source of explosive, and a programme of antibiotic prophylaxis for potentially exposed people (eventually 32 000 were treated) was initiated. The US government ordered a large quantity of ciprofloxacin from Bayer Pharmaceuticals, which was welcome since the company was still recovering from the global withdrawal of its cholesterol-lowering agent cerivastatin [4]. Since anthrax is normally sensitive to standard antibiotics such as penicillin and tetracycline, the implication of this order was that the strain of the bacillus used might have been deliberately rendered resistant. The US government caused some unease in the industry by threatening to buy generic ciprofloxacin unless Bayer cut the price of its patent-protected drug substantially. After stockpiling some 120 million ciprofloxacin tablets the Centers for Disease Control (CDC) changed its advice and began to recommend doxycycline for prophylaxis [4]. The perpetrator has yet to be apprehended: suspicion currently points to a disgruntled government research worker. Heightened awareness of the real threat from terrorist activity, and bioterrorism in particular, has led to a number of consequences, many of them relevant to the pharmaceutical industry. The CDC has updated its assessment of potential bioterrorism agents [5]; in addition to well-recognized (category A) threats, such as smallpox, anthrax, plague and viral haemorrhagic fevers, the list has a category B for less lethal agents, including organisms causing food poisoning, and a category C for emerging threats, such as Nipah virus and hantavirus. The US government is requesting an extra $1.5 billion to fight bioterrorism [6], some of which will be spent on stockpiling vaccines and antibiotics, the rest on research and development. Anthrax and smallpox are recognized as particular problems. The need for new antibiotics, antitoxins and vaccines against anthrax has become clear [7]. The US Food and Drugs Administration (FDA) has already (March 2002) issued a ‘Guidance for Industry’ on developing antimicrobial drugs for post-exposure prophylaxis of inhalational anthrax (http:// www.fda.gov/cder/guidance/index.htm). Smallpox was considered to have been eradicated and vaccination was discontinued in the 1970s; the level of herd immunity is now so low that deliberate infection could cause a major epidemic [8]. Although in theory only the USA and Russia possess stocks of the virus, it is strongly suspected that ‘rogue nations’ such as Iraq may have obtained specimens. It is also possible that related viruses such as camelpox and monkeypox could be engineered to become pathogenic in humans, or even that terrorists might obtain viable smallpox virus from 20th century victims buried in the Arctic permafrost [9]. Recently, an orally active derivative of the antiviral agent cidofovir has been shown to be highly active against smallpox in vitro, and in a mouse (cowpox) model [10]. 1364-9027 # 2002 LIPPINCOTT WILLIAMS & WILKINS 64 SNELL No-one has reported studying the antiviral methisazone, which was used in the prophylaxis and treatment of smallpox in the 1960s, reportedly with some success. The US government recently placed a large order for smallpox vaccine with the UK company Acambis; its share price rose, only to fall again when Aventis Pasteur announced that it had discovered 85 million doses of smallpox vaccine in storage in Pennsylvania since 1958, which it had offered to donate to the US government. In the most recent twist to the saga the UK government placed an order for smallpox vaccine with a rival UK company, Powderject, only to face accusations of ‘cronyism’ when it emerged that the company was a Labour party benefactor. So far the effects of actual and potential bioterrorism have been financially beneficial to the industry, but we all share a small and increasingly more hazardous planet – even if it has been suggested that bioweapons pose more of a psychosocial threat than a physical danger [11]. Certainly after the events of last Autumn, the world will not be the same. INTERNATIONAL JOURNAL OF PHARMACEUTICAL MEDICINE References 1 Gorka S, Sullivan R. Biological weapons and the pharmaceutical industry. Int J Pharm Med 2000; 14:213–218. 2 Geissler E, van Courtland Moon J, editors. Biological and toxins weapons: research, development, and use from the middle ages to 1945. Oxford: Oxford University Press; 1999. 3 May K. The Collison nebuliser: description, performance and application. J Aerosol Sci 1973; 4:235–243. 4 Charatan F. Bayer cuts price of ciprofloxacin after Bush threatens to buy generics. Br Med J 2001; 323:1023. 5 Rotz L, Khan A, Lillibridge S, Ostroff S, Hughes J. Public health assessment of potential biological terrorism agents. Emerg Infect Dis 2002; 8:225–230. 6 Stewart V. Biotech draws its battlelines against bioterrorism. Scrip Magazine 2001 (December). pp. 6–7. 7 Young J, Collier R. Attacking anthrax. Sci Am 2002; 286(3):36–45. 8 Gani R, Leach S. Transmission potential of smallpox in contemporary populations. Nature 2001; 414:748–751. 9 Enserink M, Store R. Dead virus walking. Science 2002; 295:2001–2005. 10 Bradbury J. Orally available cidofovir derivative active against smallpox. Lancet 2002; 359:1041. 11 Moscrop A. Mass hysteria is seen as main threat from bioweapons. Br Med J 2001; 323:1023. 2002 G Vol 16, No. 2