Viruses as agents of mass destruction

Recent events in the US, with the release of Anthrax Bacillus from as yet unknown sources, have for the first time in most people’s lifetime focussed the world’s attention on the threat of biological warfare. However, such attacks are not new. From time to time throughout history peoples and governments around the world have used microorganisms as efficient and cost-effective weapons of mass destruction. Starting in a rather crude but effective way, the Greeks and Romans deposited dead animals into their enemies’ drinking water. Later dead soldiers were added to this, and the technique was further refined in Medieval times when bodies of people who had died of infectious diseases were catapulted into towns under siege. Copyright Royal Medical Society. All rights reserved. The copyright is retained by the author and the Royal Medical Society, except where explicitly otherwise stated. Scans have been produced by the Digital Imaging Unit at Edinburgh University Library. Res Medica is supported by the University of Edinburgh’s Journal Hosting Service url: http://journals.ed.ac.uk ISSN: 2051-7580 (Online) ISSN: ISSN 0482-3206 (Print) Res Medica is published by the Royal Medical Society, 5/5 Bristo Square, Edinburgh, EH8 9AL Res Medica, Autumn 2002 : 3-6 doi: 10.2218/resmedica.v0i0.995 Viruses as Agents of Mass Destruction Dorothy H Crawford Professor of Medical Microbiology, University o f Edinburgh Recent events in the US, with the release of An­ thrax Bacillus from as yet unknown sources, have for the first time in most people’s lifetime focussed the world’s attention on the threat of biological warfare. However, such attacks are not new. From time to time throughout history peo­ ples and governments around the world have used microorganisms as efficient and cost-effec­ tive weapons of mass destruction. Starting in a rather crude but effective way, the Greeks and Romans deposited dead animals into their en­ emies’ drinking water. Later dead soldiers were added to this, and the technique was fur­ ther refined in Medi­ eval times when bodies of people who had died of in­ fectious diseases were catapulted into towns under siege. Once the true na­ ture of microorgan­ isms became clear in the nineteenth and early twentieth cen­ turies, the ability to grow large stocks of bacte­ ria and viruses meant that biological warfare as­ sumed global significance. Although there are no clearly documented incidences of the use of biological warfare during World War 1, the threat was fully appreciated, and accusations, counteraccusations and denials abounded. Hence the 1925 Geneva Protocol prohibited the use of bio­ logical methods as well as poisonous gases in warfare; but it did not ban their further develop­ ment In 1929 the Russians set up a biological war­ fare research station north of the Caspian Sea, prompting Britain, Japan, the USA and Canada to do the same. The Japanese developed the most extensive programme, and in the years leading up to and during World War II, they used human subjects in open field trials to test out their le­ thal agents including the bacteria causing plague, cholera, glanders and typhus. Manufacture con­ tinued in some countries until The Biological and Toxic Weapons Convention came into effect in 1975. This certainly reduced the threat, but did not entirely eliminate it, and the problem of treaty verification has continued ever since 2. In the modem world the threat of biological warfare comes mainly from terrorist groups and third world dictators. For them biological weap­ ons have many advan­ tages over their con­ ventional counter­ parts, being cheaper and relatively easy to prepare. Although new restrictions are in place, seed cultures of many dangerous mi­ croorganisms can still be obtained relatively easily from national collections. And since researching and preparing vaccines (defensive research) is a legitimate reason for growing microbes on a large scale, biological weapons factories (offensive research) can mas­ querade as vaccine production plants. Clearly, Iraq is a case in point; six such facilities are known to have existed, including the Daura Foot and Mouth Disease Vaccine Facility at Al Manal. In 1991 when Iraqi troops occupied Kuwait, it was well known that they had a stockpile of weapons laden with biological agents including 200 bombs and 25 ballistic missiles. Combat troops in Operation Desert Storm were vacci­ nated, provided with protective equipment, and given prophylactic antibiotics. Thankfully, in the event, none of these were required 3. Microorganisms are ideal for selective attacks on individuals or for targeting large metropolises. “Microorganisms are ideal for selective attacks on individuals o r f o r t a r g e t i n g l a r g e metropolises. They can be smuggled undetected through all traditional security devices, and tiny volumes can kill huge numbers o f people. ”


Dorothy H Crawford Professor o f Medical Microbiology, University o f Edinburgh
Recent events in the US, with the release of An thrax Bacillus from as yet unknown sources, have for the first time in most people's lifetime focussed the world's attention on the threat of biological warfare.However, such attacks are not new.From time to time throughout history peo ples and governments around the world have used microorganisms as efficient and cost-effec tive weapons of mass destruction.Starting in a rather crude but effective way, the Greeks and Romans deposited dead animals into their en emies' drinking water.Later dead soldiers were added to this, and the technique was fur ther refined in Medi eval times when bodies of people who had died of in fectious diseases were catapulted into towns under siege.
Once the true na ture of microorgan isms became clear in the nineteenth and early twentieth cen turies, the ability to grow large stocks of bacte ria and viruses meant that biological warfare as sumed global significance.Although there are no clearly documented incidences of the use of biological warfare during World War 1, the threat was fully appreciated, and accusations, counteraccusations and denials abounded.Hence the 1925 Geneva Protocol prohibited the use of bio logical methods as well as poisonous gases in warfare; but it did not ban their further develop ment In 1929 the Russians set up a biological war fare research station north of the Caspian Sea, prompting Britain, Japan, the USA and Canada to do the same.The Japanese developed the most extensive programme, and in the years leading up to and during World War II, they used human subjects in open field trials to test out their le thal agents including the bacteria causing plague, cholera, glanders and typhus.Manufacture con tinued in some countries until The Biological and Toxic Weapons Convention came into effect in 1975.This certainly reduced the threat, but did not entirely eliminate it, and the problem of treaty verification has continued ever since 2.
In the modem world the threat of biological warfare comes mainly from terrorist groups and third world dictators.In h aled virus p articles infect cells o f the upper resp iratory passag es, and after an incubation p e riod o f 12-14 days victim s d ev elop high fever and m alaise w ith head-and b a ck -ac h es.T he characteristic pustular rash appears 1-2 days later, b eg in n in g in the m outh and p h arynx and th ere a fte r spread in g to the face, arm s, trunk and legs (see figure).T he p u stules begin to cru st after 8-9 days and ev en tu ally the scabs separate leaving pitted scars, p articularly on the face 5. war-heads of guided missiles and sent to its des tination still in a viable condition.Also, since smallpox was eradicated in 1977, almost half of the World's population is non immune and would by now be susceptible.Furthermore, the amount of protection afforded by a vaccination given over 20 years ago is unclear.The infectious dose of virus is thought to be very low (1-2 virus par ticles), and so disease would occur in almost everyone who became infected.In addition to this, although the threat of a deliberate smallpox release is well recognised by governments and stocks of vaccine have been retained for this eventuality, in reality it would not be possible to vaccinate an entire population in time to prevent an epidemic spreading, probably on a world-wide scale.

Ebola Haemorrhagic Fever
Viral haemorrhagic fever is a syndrome which can be caused by a number of RNA viruses from different virus families.The syndrome charac teristically begins abruptly with a high fever, headache, malaise, myalgia, fatigue, diarrhoea and bleeding.Increased vascular permeability resulting from viral infection of vascular en dothelium initially causes petechial haemor rhages, which progress to generalised bleeding into mucous membranes and internal organs.Depending on the particular organs affected, patients develop neurological, pulmonary and/ or hepatic features, with eventual hypotension, cardiovascular collapse, shock and renal failure.Disseminated intravascular coagulation is an other prominent feature, and with no specific treatment to offer, mortality is very high.
Ebola virus was first isolated from an outbreak of haemorrhagic fever in Yambuku, a remote jungle village in Northern Zaire, in 1976.How ever, it is probable that the virus had caused lo calised outbreaks in rural Africa prior to this time, and several subsequent outbreaks have been documented.On each occasion the virus has infected man from an unknown source, and this suggests that there must be a reservoir of infec tion, probably an animal in the rain forest which carries the virus as a harmless passenger.Until this animal is identified sporadic, unpredictable outbreaks will continue to occur.
The first outbreak of Ebola was typical.The index case was a school teacher who had just returned from a trip through the bush when he became unwell with fever and malaise.He went to the local mission station, where the Belgian nuns assumed he had malaria and gave him an injection of antimalarials.As was their practice, they then used the same needle throughout the day to inject others.By the time the school teacher died a few days later there were many other cases, including his family and several of the nuns.In all 318 people contracted the dis ease and 280 died.The outbreak was only brought under control when the necessary con trol measures were implemented.
Ebola is not endemic in the human population, and therefore any outbreak requires an initial infection, probably through a bite from the ani mal which harbours the virus naturally.How ever, once the virus has crossed the species bar rier and infected man, it can spread from person to person very effectively by direct contact.Pa tients are highly infectious since all body fluids contain large amounts of infectious virus.Thus in the Yambuku outbreak the virus spread via a contam inated needle to other patients and through routine contact and nursing procedures to the nuns and family members.
As a weapon of mass destruction Ebola virus certainly has its attractions, in particular it's high infectivity, the devastating nature of the disease, the high mortality, and the lack of preventive or therapeutic measures.But although devastating, Ebola outbreaks generally remain localised.This is because the virus is spread by direct contact and not by aerosol, and the short incubation pe riod (may be only 4 days) and severe symptoms prevent patients travelling far from the site of infection.Thus once the necessary isolation pre cautions (strict barrier nursing) are in place, it is relatively easy to bring the outbreak under con trol.

Conclusions
Biological weapons are primarily designed to destroy all vital activity but not necessarily to wipe out the whole human race.In this regard, smallpox, while it would certainly incapacitate, would probably not kill all those infected because of our inbuilt resistance which developed and strengthened over the centuries when the virus was rife.We have no such inbuilt resistance to Ebola, but a world-wide epidemic of this virus would be very difficult to engineer because of its localised method of spread.
After the world-wide elimination of smallpox, the World Health Organisation (WHO) recom mended that all laboratories destroy their stocks of the virus, and two WHO reference laborato ries were set up: The Institute of Virus Prepara tions in Moscow, Russia, and the Centre for Dis ease Control in Atlanta, USA.These remaining stocks were due to be destroyed by the end of the twentieth century, but were in fact retained for further research when the potential threat was realised.According to a former Deputy Direc tor of the Soviet Union's Civilian Bioweapons program, smallpox virus from these stocks has been used to grow up large quantities for use in bombs and missiles.And, to end this review with the most frightening information (hopefully only a rumour), work was apparently underway to produce more virulent and infectious strains, perhaps even a hybrid combining the worst fea tures of Ebola and smallpox.With the break up of the Soviet Union there are now fears as to whose hands these potentially highly lethal weap ons may fall into 5.
T h e y can be sm u g g le d u n d e te c te d th ro u g h all traditional security d evices, and tiny v o lu m es can kill h u g e n u m b ers o f p eople.F u rth erm o re, since they are in v isib le, o d o u rless, tasteless an d have a d elay ed action, so th ey can be released into the air w ith o u t im m ed iate detection.A m ajo r b io log ical attack w ould place u n to ld strain on m e d i cal serv ices w h ich are n o t d e sig n ed to co p e w ith such an incident.A s w e h av e no p rev io u s e x p e rien ce d ealin g w ith this type o f attack, it is likely that pan ic and p sy ch o lo g ical trau m a w o u ld lead to total co n fu sio n 4. M an y d ifferen t o rg an ism s have been tested for th eir poten tial as ag en ts o f b io lo g ical w arfare, in clu d in g b acteria w hich cau se anth rax , T B , ty phoid, plag u e, ch o lera, gas gan g ren e. C an d id ate viru ses in clu d e the h aem o rrh ag ic fe v e r viruses, like E bola, and sm allpox.T he re m a in d e r o f this rev iew w ill focus on these tw o o rganism s.Smallpox S m allp o x virus w as p ro b ab ly the first m icrobe to be used as a w eap o n o f m ass d estru ctio n .It is likely that d elib erate release o f sm allp o x virus o ccu rred on several o ccasio n s d u rin g the N orth A m erican Indian W ars, but the best d o cu m en ted in cid en t w as in 1763.A t the tim e Indian scalpin g -p a rtie s w ere d e v a sta tin g E u ro p e a n s e ttle m en ts in the a rea su rro u n d in g F o rt P itt (n ow P ittsburgh) cau sin g w id esp read fear and panic.S ir J e ffre y A m h e rst.B ritish C o m m a n d e r-in -C h ie f in N orth A m erica, k n o w in g that troop re in fo rcem en ts w ould not be fo rth co m in g , feared that the w h o le o f W estern P e n n sy lv an ia w o uld soon be lost.In the k n o w led g e that the Indians w ere p a rtic u la rly su sc e p tib le to sm a llp o x , he authorised sm allp o x -co n tam in ated blankets to be d istrib u ted am o n g the N ative A m erican tribespeo p le '.U n til th e tw e n tie th c e n tu ry sm a llp o x w as a killer on a w o rld -w id e scale.T he virus spread rapidly in large and cro w d ed cities cau sin g d e v astatin g ep id em ics.C ase fatality rates reached 30% , o r even h ig h e r in p o p u latio n s w ho had not p re v io u s ly e n c o u n te re d sm a llp o x .T h e v iru s spread from p erson to p erson prim arily through the air via d ro p lets from the o ro p h ary n x ; m ore rarely from direct contact w ith m aterials co n tam i nated w ith pock fluid o r scabs.In m ost c o m m u n ities sm allpox ep id em ics o ccurred regularly, and since nearly all adults w ere im m une, c h il dren w ere the m ain victim s.H ow ever, unlike the o th e r a ir-b o rn e ch ild h o o d in fe c tio n s (su ch as m easles, m um ps, chick en p o x ), sm allpox tended to sp read w ithin hou seh o ld s ra th er than in the p o p u latio n at large.T his w as probably due to the fact th at su ffe re rs only b e cam e in fectio u s w hen the rash appeared, by w hich tim e they w ere likely to be co n fin ed to bed.

From
the p o in t o f view o f the aggressor, one o f the m ain features o f sm allp o x w hich m ake it a desirab le agent for biological w arfare is the fact that it rem ains in fectious for relatively long p e riods o f tim e, particularly in cold, d am p c o n d i tions.T his m eans that it could be packed into