A Weekly News Digest of Applied Science
October 22, 2001 -- Vol. 1 Number 19


J. Carey et al (BW) discuss bioterrorism. Easily produced germ weapons could wreak even greater chaos than suicide pilots in hijacked planes. The facilities for breeding bioweapons, from small factories down to a laboratory bench, are almost impossible to pinpoint or track. Indeed, because of modern biotechnology, producing a supply of deadly germs is easier than ever. "The same fermenter used to make beer or a drug can grow anthrax an hour later." In addition, gene-splicing makes it theoretically possible to engineer super-microbes deadlier than anything nature has created. Even if terrorists cannot produce such microbes themselves, they might buy supplies from Saddam Hussein or hire a few of the tens of thousands of former Soviet bioweapons scientists cast adrift when the bioweapons facilities of their country shut down. According to some reports, Osama bin Laden has been attempting to create a bio-arsenal. September 11th proved that hate and extremism have swept aside the political and moral restraints that once discouraged terrorists from mass slaughter. In a recent simulation exercise called "Dark Winter", Iraqi- financed Afghan terrorists spray smallpox viruses into shopping malls in three cities in the west, east, and south. The attack goes unnoticed until 9 to 14 days later when people begin showing up in emergency rooms complaining of fever and rash. In an attempt to contain and fight the outbreak, one governor shuts his state's airports, closes the borders, and orders vaccinations for all medical personnel. The actions anger federal authorities and the military, who want to save limited vaccine supplies for the armed forces. But it is too late, since by then, each victim has infected at least 10 others, some of whom are already spreading contagion in other states. According to this scenario, as the horror spreads, "everything spins out of control". Commerce comes to a halt; even food deliveries stop. Nationwide air travel and the stock market shut down. Vaccine supplies are quickly depleted, and within 3 weeks, 16,000 people are sick and more than 5000 of them will die. After 2 months, 3 million people are infected and 1 million will die. And still, the epidemic continues to grow.

BW 2001 1 Oct

Editor's note: It should be noted that the report briefed above appeared in BusinessWeek, a leading business magazine, and that a similar notice of danger of a smallpox attack appeared in an editorial in the New York Times of 26 September. We have no opinion about the validity of specific bioterrorism simulations, although the possible casualties and chaos produced by such an attack seem enormous. The background material below primarily concerns smallpox. Additional material can be found in the recent PRAXIS issue of October 1, 2001.

PRAXIS 22 Oct 2001

-------- Related Background: SMALLPOX AS A BIOLOGICAL WEAPON

D.A. Henderson et al report an attempt to develop consensus-based recommendations for measures to be taken by medical and public health professionals following the use of smallpox as a biological weapon against a civilian population. The authors make specific recommendation regarding smallpox vaccination, therapy, post-exposure isolation and infection control, hospital epidemiology and infection control, home care, decontamination of the environment, and additional research needs. The authors suggest that in the event of an actual release of smallpox and subsequent epidemic, early detection, isolation of infected individuals, surveillance of contacts, and a focused selective vaccination program will be the essential items of an effective control program. The authors state: "The specter of resurgent smallpox is ominous, especially given the enormous efforts that have been made to eradicate what has been characterized as the most devastating of all the pestilential diseases."

JAMA 1999 281:2127 SW Bulletin 1999 16 Jun

PRAXIS 22 Oct 2001

-------- Related Background: ON BIOLOGICAL TERRORISM

Although political events during the past decade have reduced fears of biological warfare among the major powers, the pathogens likely to be used in such warfare have not vanished, and there is now an apparent growing concern about the use of such pathogens in acts of biological terrorism ("bioterrorism").

Donald A. Henderson (Johns Hopkins University, US) presents a review of current views, expectations, and contingency plans, the author making the following points concerning the scientific fundamentals: 1) The expected scenario following release of an aerosol cloud of a biological agent is entirely different from that following an attack of nuclear or chemical terrorism. A biological agent aerosol release could be silent and would almost certainly be undetected. The cloud would be invisible, odorless, and tasteless. It would behave much like a gas in penetrating interior areas, and the release would not be suspected for days or weeks later. 2) The implicit assumption has frequently been that chemical and biological threats and the responses to them are so generically similar that they can be readily handled by a single "chembio" expert, usually a chemist. This is a serious misapprehension. 3) Any of thousands of biological agents that are capable of causing human infection could be considered a potential biological weapon, but realistically only a few pose serious problems. Only a very small number of species of these pathogens can be cultivated and dispersed effectively so as to cause cases and deaths in numbers that would threaten the functioning of a large community. The current consensus is that there are 11 pathogens "very likely to be used." *Smallpox, *plague, *anthrax, and *botulism are considered the top four candidates. The others are *tularemia, *glanders, *typhus, *Q fever, *Venezuelan equine encephalitis, *Marburg virus, and *influenza virus. 4) Any group with sufficient resources could purchase prepared supplies of aerosolizable organisms and could transport them easily, because only small quantities are needed to inflict casualties over a wide area. No mechanisms currently exist for screening to intercept such materials at state or national borders. 5) Of the potential biological weapons, smallpox and anthrax pose by far the greatest threats, but these pathogens have different clinical and epidemiological properties. Smallpox poses an unusually serious threat, in part because virtually everyone is now susceptible, vaccination having stopped worldwide 20 or more years ago as a result of the eradication of the disease. It is probable that no more than 20 percent of the world population is protected; for the unprotected, fatality rates after infection are 30 percent. Another problem is that there are no longer any manufacturers of smallpox vaccine, which means large-scale vaccination immediately after an outbreak is currently not possible. 6) Concerning an inhalation anthrax epidemic, the scenario is as dangerous as that for smallpox. After 2 to 3 days anthrax-infected individuals would appear in emergency rooms and doctors' offices with a variety of nonspecific symptoms such as fever, cough, and headache. Within a day or two, patients would become critically ill and then die within 24 to 72 hours. The fatality rate for anthrax is 80 percent or greater. 7) The author concludes: "Once the medical community rallied... in educating peoples and policymakers everywhere about the dread realities of a nuclear winter. Perhaps the same should now be done with respect to the realities of biological weapons, which are now considered to be a more serious threat than the nuclear ones."

SCI 1999 283:1279


*Smallpox: This is an acute eruptive contagious disease caused by a poxvirus (Orthopoxvirus, a member of the family Poxviridae). The average incubation period is 8 to 14 days. Following the incubation period, the onset symptoms are constitutional: chills, high fever, backache, headache. In from 2 to 5 days, these symptoms subside and the skin eruptions appear. Considering the temporal course of the disease, a smallpox epidemic would probably not become evident until 2 to 3 weeks after release of an aerosol.

*plague: In this context, this term refers to the acute infectious disease caused by the bacterium Yersinia pestis, the disease marked by high fever, toxemia, and prostration. The pathogen is usually transmitted to man by fleas that have bitten infected rodents, and there are various forms of the disease. The incubation period is 2 to 7 days. The fatality rate is near 50 percent, with usually 100 percent fatality for the pneumonic form of the disease.

*anthrax: This disease is caused by the bacterium Bacillus anthracis, and is usually transmitted by infected animals through traumatized human skin. The disease is marked by hemorrhage and blood effusions in various organs and body cavities, and by symptoms of extreme prostration. In the context of this report, the disease entity of concern is "inhalation anthrax", which is a more serious human disease than anthrax contracted from an animal through the skin. Inhalation anthrax produces hemorrhagic pneumonia with shock and is usually fatal (fatality above 80 percent).

*botulism: This disease is caused by toxins of the bacterium Clostridium botulinum, an organism common in soil and sometimes in animal feces. Symptoms appear 18 to 24 hours after entry of the toxins, and the most severe symptoms are the result of effects on the neuromuscular system. Death occurs from respiratory paralysis or cardiac arrest. The fatality rate is high. Ordinarily, botulism is not an actual human infection, since the human disease is almost always caused by ingestion of food contaminated with toxins produced by C. botulinum, which is anaerobic and grows only under conditions of low or absent oxygen (e.g., in canned foods). The botulinum toxins are among the most highly toxic substances known: the lethal dose for a human is estimated to be in the range 1 to 2 micrograms.

*tularemia: This disease is caused by the bacterium Francisella tularensis, a pathogen usually transmitted to humans by biting arthropods (e.g., insects), direct contact with infected animal tissue, ingestion of contaminated food or water, and inhalation of aerosols. Apparently, inhalation of only 50 individual F. tularensis bacteria can result in infection. Symptoms appear within a week. The disease can usually be controlled with antibiotics.

*glanders: A common disease of horses, mules, and donkeys, caused by the bacterium Burkholderia mallei. The inhalation form of the disease may lead to primary pneumonia. The disease can usually be controlled with antibiotics.

*typhus: A group of acute infectious and contagious diseases caused by the bacterial group Rickettsaie. These diseases are characterized by fever, headache, malaise, and prostration.

*Q fever: Also caused by a Rickettsaie bacterium, but the symptoms resemble influenza, nonbacterial pneumonia, hepatitis, or encephalopathy.

*Venezuelan equine encephalitis: This is a viral disease usually transmitted by mosquitoes from horses to humans. It is caused by a togavirus, subgroup alphavirus. In humans, the symptoms are similar to those of influenza.

*Marburg virus: One of the two notorious African Hemorrhagic Fevers (the other is Ebola virus), highly virulent, with infections usually ending in death. These viruses have the highest mortality rate (as much as 90 percent) of all the viral hemorrhagic fevers. The disease was first recognized in 1967.

*influenza virus: Any of a group of influenza viruses, all of the family Orthomyxoviridae. The influenza diseases usually have a sudden onset, are highly contagious, and easily produce large-scale epidemics. Apparently, if only a few cells of the respiratory *epithelium are infected by deposited virus particles, the infection can proceed. The severity of symptoms and the outcome depends on which strain of the virus is the pathogen.

*epithelium: In animals and humans, epithelial cells compose the cell layers that form the interface between a tissue and the external environment, for example, the cells of the skin, the lining of the intestinal tract, and the lung airway passages.

-------- SW 1999 21 May

PRAXIS 22 Oct 2001


The last case of confirmed smallpox on Earth occurred more than 20 years ago, and nearly 2 decades ago the World Health Organization concluded the global eradication of smallpox had been achieved. But new questions have now arisen: a) Could recent outbreaks of human monkeypox in Africa represent the return of another form of smallpox? b) Could smallpox virus be used as a weapon of biological terrorism? c) What are the implications of the decision of the World Health Organization to advise the destruction of all isolates of the smallpox virus in June 1999?

In a short review of these questions, Breman and Henderson make following points: 1) The available data do not support the possibility that monkeypox might soon take over the ecological niche left vacant by smallpox. 2) All vaccination against smallpox ceased after eradication of the disease was affirmed. Virtually all children and many adults are now fully susceptible to smallpox. Only limited supplies of vaccine are available. 3) Were smallpox virus released by an act of terrorism, the results could be catastrophic. A large proportion of the population has no immunity. There is little available vaccine and no effective treatment. The expected case fatality rate would be higher than 25 percent. The authors conclude: "Reports suggesting that monkeypox might replace smallpox as a serious epidemic threat are unsubstantiated, but the threat posed by the possible use of smallpox as a terrorist weapon is genuine. Because of the gravity of this threat, all known stocks of variola [smallpox] virus should be destroyed as soon as possible. The deliberate deployment of this virus must be discouraged by whatever means possible."

NEJM 1998 339:556 SW 1998 18 Sep

PRAXIS 22 Oct 2001


The largest and most complex animal viruses are the poxviruses, among them smallpox and a related virus called monkeypox. Smallpox was ostensibly eradicated completely in 1979, and the disease is more or less extinct, with debate now about whether to completely extinguish the smallpox genome by destroying the last of it in storage. Monkeypox, however, is far from eradicated. Until recently the disease exhibited minor outbreaks, with the incidence being quickly damped due to the apparent difficulty of human to human transmission. In these outbreaks, the disease was evidently transmitted by eating the meat of infected monkeys, squirrels, and rats. Now, however, during the last year, there has been a striking outbreak of 92 cases of monkeypox, all within a few villages in the central part of the Democratic Republic of Congo, and the most troubling aspect is the evidence that the rate of human to human transmission may have suddenly increased many-fold over what it has been in the past. Has the monkeypox virus mutated to a more virulent form more easily transmitted from one person to another? Medical epidemiologists are alarmed. Peter Jahrling, a virologist at the U.S. Army Medical Research Institute (MD US) says, "I hate to be accused of pushing the alarmist button, but for practical purposes smallpox is back." And Ali Khan, a medical epidemiologist at the U.S. Center for Disease Control and Prevention, who recently visited the area of the Congo in question, says, "I am personally concerned about what would happen if this disease showed up in a major city." But other virologists and epidemiologists, including some who specialize in the poxviruses, are not convinced that human to human transmission of monkeypox has actually increased substantially. An argument can be made that the natural immunity of the people of the Congo has been compromised by a high incidence of HIV and the vicissitudes of armed conflict in the area. The debate goes on, and the cases in the central Congo keep mounting.

SCI 1997 18 Jul SW 1997 29 Jul

PRAXIS 22 Oct 2001


As the story goes, in the year 1793 in Wildbad, Germany, 13 people sharing an uncooked smoked sausage that had been sitting for hours became ill and 6 died. To describe their illness, the word "botulism", from the Latin _botulus_, meaning "sausage", came into use. It took more than a century before it was understood that the skin of the sausage had made the meat below it low in oxygen content, so that with enough time the common bacterial organism Clostridium botulinum could multiply and produce enough toxin to make the sausage extremely lethal. The organism C. botulinum, an *anaerobic spore-forming bacillus, is distributed throughout the environment, particularly in ordinary soil. When the spores contaminate preserved or canned foods with low oxygen levels and nutrients that support growth, the spores germinate and the clostridium bacteria soon begin producing toxins. Botulinus (or botulinum) neurotoxins (there are a number of types) are the most potent toxins known. The toxins are heat-labile, so properly heated foods do not produce the toxic condition called "botulism". In general, the toxin acts on the peripheral nervous system by inhibiting the release of acetylcholine at cholinergic synapses such as the neuromuscular junction. This causes a muscular paralysis that is usually fatal. This report concerns botulinum toxin as a biological weapon of warfare or terrorism. Although biological warfare is usually treated as a modern phenomenon, its history is more than 600 years old. In 1347, in the siege of Caffa in the Crimea, the Mongols apparently hurled bodies of plague victims over the walls protecting the Genoese defenders. Subsequently, Genoese ships carried the plague bacillus (Yersinia pestis) to Europe with the resultant extensive epidemic known as the "Black Death". In World War I (1914-1918), the Germans apparently infected Romanian cavalry horses, and US livestock destined for shipment to the Allies, with glanders, a lesion-producing bacterial disease. Charges of germ warfare were made by the Chinese against United Nations forces in the Korean War of 1950-1953, but there was no substantiation of these charges. More recently (see below) there has been evidence of both intended and actual use of botulinum toxin for either military or terrorist purposes.

S.S. Arnon et al (18 authors at 10 installations, US) present a report on botulinum toxin as a biological weapon, the authors making the following points:

  1. The authors point out that botulinum toxin is the most poisonous substance known. A single gram of crystalline toxin, evenly dispersed and inhaled, would kill more than 1 million people, although technical factors would make such dissemination difficult. The basis of the phenomenal potency of botulinum toxin is enzymatic: the toxin is a zinc proteinase that cleaves one or more of the [membrane-] fusion proteins involved in the release of the neurotransmitter substance acetylcholine by neuronal synaptic vesicles into the neuromuscular junction. In this system, acetylcholine activates muscle fibers, and if acetylcholine release is prevented, nerve fibers have no means of activating these muscle fibers, and the muscle is effectively paralyzed.
  2. In the US, botulinum toxin is licensed for treatment of various diseases and conditions, including migraine headache, lower back pain, stroke, etc. Therapeutic botulinum toxin, however, is an impractical bioterrorist weapon: a vial of a typical therapeutic preparation of botulinum toxin contains only approximately 0.3 percent of the estimated lethal human inhalation dose, and 0.005 percent of the estimated lethal oral dose.
  3. Terrorists have already attempted to use botulinum toxin as a bioweapon. Between 1990 and 1995, aerosols containing botulinum toxin were dispersed at multiple sites in downtown Tokyo (JP) and at US military installations in Japan on at least 3 occasions, the dispersals by the Japanese cult Aum Shinrikyo. These attacks apparently failed because of faulty microbiological technique, deficient aerosol-generating equipment, or internal sabotage. The perpetrators evidently obtained C. botulinum from soil they had collected in northern Japan.
  4. Military development and use of botulinum toxin evidently began in the 1930s. The head of the Japanese biological warfare group known as "731" admitted to feeding cultures of C. botulinum, with lethal effect, to prisoners during the Japanese occupation of Manchuria in the 1930s. The US biological weapons program first produced botulinum toxin during World War II (1939- 1945). Evidently, because of concerns that Nazi Germany had weaponized botulinum toxin, more than 1 million doses of botulinum toxoid vaccine were made for Allied troops preparing to invade Normandy on D-Day.
  5. Four of the countries currently listed by the US as "state sponsors of terrorism" (Iran, Iraq, North Korea, Syria) have developed, or are believed to be developing, botulinum toxin as a weapon. After the 1991 Persian Gulf War, Iraq admitted to the United Nations inspection team to having produced 19,000 liters of concentrated botulinum toxin, of which approximately 10,000 liters were loaded into military weapons. These 19,000 liters of concentrated toxin are currently not fully accounted for, and they constitute approximately 3 times the amount needed to kill by inhalation the entire present human population of the world. In 1990, Iraq deployed specially designed missiles with a 600-kilometer range, and 13 of these missiles were filled with botulinum toxin, 10 with *aflatoxin, and 2 missiles with *anthrax spores. Iraq also deployed special 180-kilogram bombs for immediate use, with 100 bombs containing botulinum toxin, 50 bombs containing anthrax spores, and 7 bombs containing aflatoxin. As far as is known, Iraq weaponized more botulinum toxin than any other of Iraq's known biological agents.
  6. Concerning the chemistry of botulinum toxin, the authors point out that botulinum toxin is a simple di-chain polypeptide that consists of a 100-kilodalton heavy chain joined by a single disulfide bond to a 50-kilodalton light chain. The 3-dimensional structure of botulinum toxin was recently resolved to 3.3 angstroms. The toxin's light chain is a Zn(++)-containing *endopeptidase that blocks acetylcholine containing vesicles from fusing with the terminal membrane of the motorneuron axon, this resulting in flaccid muscle paralysis. The estimated human lethal dose (70 kilogram individual) of botulinum toxin is approximately 0.09 to 0.15 micrograms intravenously or intramuscularly, 0.70 to 0.90 micrograms by inhalation, and 70 micrograms orally.

JAMA 2001 285:1059


*anaerobic: In general, requiring an absence of oxygen.

*aflatoxin: A potent toxin produced by a species of mold (Aspergillus flavus), the organism a frequent contaminant of peanuts, corn, grains, and other foods.

*anthrax: See related background material below.

*endopeptidase: (endoproteinase; proteinase) In general, any enzyme that hydrolyzes non-terminal peptide bonds in oligopeptides.

SW 2001 9 Mar


C. Arnst and W.C. Symonds (BW) discuss the new attitude towards the nature of nuclear threats. The ramming of a jetliner into a nuclear power plant would not produce a nuclear bomb, but the release of radioactive contamination would produce a major radioactive fallout. National security experts have been warning for years that the US is vulnerable to a terrorist attack using weapons of mass destruction such as nuclear bombs, but the federal government tended to downplay these warnings. But after the September 11 attacks, trained anti-nuclear-weapon teams are now on alert. Many consider that the most urgent and unmet national security threat to the US today is the danger that weapons of mass destruction or weapons-usable material in Russia could be stolen and sold to terrorists or hostile nation states. Missiles carrying nuclear warheads are considered unlikely terrorist threats. The more urgent and immediate threat is believed to be terrorists acquiring small-amounts of weapons- grade uranium or plutonium and building a crude but still devastating bomb. Approximately 603 tons of such materials are stored across the former Soviet Union under security conditions that are considered alarming. The production of homemade nuclear weapons is more than a hypothetical problem: the International Atomic Energy Agency reports that illicit trafficking in nuclear materials has doubled since 1996, and the agency counts 370 confirmed cases of smuggling of such materials in the past 8 years. A US State Department study has noted that as many as 130 terrorist groups worldwide have expressed interest in obtaining nuclear capabilities -- among them Osama bin Laden's Al Qaeda group. Some experts maintain that with a softball-size lump of enriched uranium, some materials mostly available at Radio Shack, and a competent university engineering graduate, one would have a reasonable chance of making a crude nuclear weapon.

BW 2001 1 Oct