Group Notes Harvey and Alyssa Smallpox and its Potential as a Biological Weapon Background Michelle Foster, a chemistry professor here at UMass, showed our class a powerpoint presentation on the history and biology of smallpox. The major points: Biology Smallpox is the common name for two variants of a poxvirus: variola major and variola minor. These viruses affect humans exclusively, although poxviruses in general are numerous and almost every species is vulnerable to some type of poxvirus. Both major and minor are highly contagious, passing from personal to person by direct contact, inhalation of droplets of body fluid (such as when someone coughs or sneezes) or (this is why smallpox is so frightening) across significant distance and barriers as an aerosol, or fine particulates which can travel on air currents in the manner of smoke. Once infected, smallpox undergoes an incubation period of 7-17 days. After this, the victim enters the prodromal phase during which mild, nonspecific symptoms begin to reveal themselves, typically a fever and flu-like achiness. Within a few days, a rash begins to appear on the forehead and face, spreading first to the trunk and then to the extremities. At this point smallpox differentiates into one of four “case types.” The reasons for this differentiation are not entirely understood but probably lie with the immune system of the host. Variola major is fatal in about 20-60% of cases depending on the virility of the strain and its particular manifestation in the host. The ordinary type produces a rash of painful papules which are clustered at the extremeties (a “centrifugal rash.”) As the disease progresses they fill with an opalescent pus which will leak out in the later stages, drying and forming a crust. These papules are most commonly discrete (they stand apart) but will occasionally run together (this is confluent-type smallpox) to produce large sheets of blistered skin. The modified type is very rarely fatal; it produces fewer and more irregular papules, and the symptoms are milder. True to its name, the flat type produces flatter lesions which may contain hemorrhages. This type is nearly always fatal. Hemorrhagic smallpox does not produce any blisters at all, but causes massive bleeding throughout the body, which first appears in the whites of the eyes and as bruises under the skin which thicken as the blood ages and turns black. This type is also usually fatal. It is believed that smallpox first appeared around 10000 BC on the African continent; from that time until very recently it has plagued almost all human societies. In the 18th century smallpox killed about 400,000 individuals on the European continent. Variolation Variolation is the process of exposing a healthy individual to weakened virus so as to stimulate an immune response that will lead to immunity against the disease. Variolation was performed in China many thousands of years ago by grinding up the scabs of victims and blowing them into the nose of the healthy. In India the same result was effected by applying pus to scored areas of skin. Obviously this method of inoculation is very risky and could result in a full-blown case of smallpox, especially in children and the elderly. The concept of inoculation traveled West with Mary Wortley Montague in 1715, wife to a British ambassador who was introduced to the process while in Turkey. Variolation was practiced in the United States by 1721. Vaccination Toward the end of the 18th century, various scientists noted that individuals who became infected with cowpox, which produced a mild disease, appeared to then be immune to smallpox. In 1796, the English scientist Edward Jenner used his new vaccine (developed from cowpox) to perform the first smallpox vaccination, on the child James Phipps. In 1800 vaccination became common in the United States. The cowpox-derived inoculation virus, called vaccinia, is still in use today Vaccinia can produce life threatening reactions in the immunse-suppressed; on average, for every one million vaccinated, 1000 have adverse reactions of whom 15 die. The vaccination confers a reliable immunity for only 3-5 years Eradication Beginning in the 1960s the WHO led the first organized effort to globally eradicate smallpox A number of characteristics made smallpox reasonably vulnerable to eradication: First and foremost, because it can only infect humans, when an entire human community is vaccinated, it has no animal reservoir to retreat into; it is forced to die It is generally only contagious once the rash begins to show, which makes identifying and isolating victims possible in a timely manner The first smallpox vaccination was crude; it left a visible scar on the upper arm, making it possible to differentiate between the vaccinated and unvaccinated The technique used to eradicate smallpox was a simple technique known as ring vaccination; once a victim was identified, an attempt was made to vaccinate all the members of their community to create buffer zone within which the smallpox was confined This technique proved successful and the WHO declared smallpox officially eradicated in 1980. Bioterrorism Smallpox has significant potential as a biological weapon, due to a number of factors: A very high morbidity and mortality rate That it can be transmitted long distances as an aerosol and inhaled It is highly contagious It is easily genetically modified That unlike many viruses it is stable outside a host Today, specimens of smallpox, officially, exist in only two locations: the CDC in Atlanta, Georgia and The State Research Center of Virology in Koltsovo, Russia. However, there is a very real possibility that there are clandestine stocks elsewhere, including in unstable countries or with hostile organizations Notes on the first half of The Demon in the Freezer, a nonfiction novel written by Richard Preston in 2002: The book opens with events that took place during the anthrax attacks following September 11, 2001 Timeline: Robert Stevens, victim #1 Thursday (9/27): Drove to Charlotte, N.C. Hiked at Chimney Rock Park Sunday: Stevens was sick to his stomach Monday: He had a high fever and became incoherent Tuesday: Brought to E.R room at JFK Medical Center Palm Beach County Thursday (10/4): Diagnosed w/ inhalation anthrax Friday: Stevens went into a coma and died Autopsy: Chest Cavity full of bloody liquid Ladled out a gallon of it Lymph nodes size and color of plums (Normal persons are size of peas) Bloody Interior saturated with hemorrhage [Spores that killed him got into his through the air](8) lungs Quotes: “Sherif Zaki…he was ladling the red liquid from Steven’s Chest, the word murder never entered his mind”(8). “…They all had terrorism on their [medical/investigators] mind”(9). Victim #2: Ernesto Blanco, was the head of mail room where Stevens worked.(9) Quotes: “Something full of spores must have arrives in the mail”(9). -Realized anthrax had not spread via nature. “…letters containing grayish, crumbly granular anthrax had arrived in NYC…to Tom Brokaw, and at CBS, ABC, and the New York Post. Several people had contracted cutaneous anthrax”(10). -Who was behind this? -letter in mail had “Death to America. Death to Israel” written on it. Key Player: John Ezzell, Anthrax specialist. -he checked out the anthrax and it appeared to be a biological weapon (14) Key Player: Eitzen “If you believe smallpox is sitting in only two freezers, I have a bridge for you to buy. The genie is out of the lamp”(19). -he suggests smallpox is in more than 2 locations. Key Player: Peter Jahrling: “Can’t catch anthrax from someone who has it, even if the victim coughs in your face-but smallpox could spread through North America like wildfire”(20). -He was worried that the powder that killed Stevens was laced w/ pox. -If it was, history could repeat itself. This served mainly to illustrate the mechanisms in place in the United States for dealing with bioweaponry threats: The Hazardous Materials Response Unit, a branch of the FBI. “When there is a serious or credible threat of bioterrorism, the HMRU will be dispatched to assess the situation and collect evidence.” –p. 13 The United States Army Medical Research Institute of Infectious Diseases (USAMRIID) which was created to develop a system of defense against bioweapons Fort Detrick, in which USAMRIID is housed, was once a center for the development of biological weapons, but this was shut down in 1969 when the US signed the Biological weapons and Toxin Convention which bans the “development, possession, or use” of these weapons.” –p. 15 The Centers for Disease Control in Atlanta, Georgia, a public health agency which oversees research on understanding, treating, and preventing diseases, including epidemiological study The novel then detours into a case study of one of the last instances of smallpox before its eradication, in the mountains of northern Germany in 1970 A young man named Peter Los was returning to Germany from Pakistan to stay with his father He became ill and was taken to the St. Walberga hospital and placed in an isolated ward Peter’s condition deteriorated and within two weeks he developed the centrifugal rash of smallpox A Doctor Richter with the State Health Department identified smallpox in a specimen from Los He immediately notified the World Health Organization, a division of the United Nations dedicated to global public health In 1966 the WHO officially began its program to eradicate smallpox led by: Donald Henderson. He was handpicked from the CDC, where as head of disease surveillance he had written a proposal for the eradication of smallpox in west Africa. The WHO ordered that Peter Los be removed from the hospital, their logic being that in the absence of anything useful that doctors could do for the disease, the hospital was only a breeding-ground for the disease in a relatively concentrated group of individuals many of whom have weak immune systems Every staff member and patient at the hospital was given the smallpox vaccine; they were then forced to remain under quarantine After someone escaped to return home, the hospital was bordered up and put under police guard A ring vaccination protocol was instituted in the surrounding community After Los, nineteen people obtained smallpox and four died, but the infection chain stopped there Game Plan: Firewall of immunized people (38) The medical team thought that if they immunized everybody who interacted with Los, as well as the people who had interacted with the people who he came in contact with then smallpox would not be able to spread as easily. “They were closing the barn door just after the horse had gone” (39). The pox vaccine can be applied 4 days after the person inhales the virus; however a day or two late with their vaccines. medics were In all, the case illustrated the effectiveness of the WHO protocol for response to a smallpox outbreak Social impact of Smallpox: It not only infected people who were around Los at the time of his outbreak, but it marked everybody who was from the same town as him. The reading stated that people with license plates from his town were not served food from certain restaurants and were not tended for at gas stations. (38) Small Pox Victim #2: Barbara Birke, died. The descriptions of her symptoms were vivid. The book explained how she was unable to talk or see her family. She passed away 4 days after she was quarantined, smallpox was a fast killer. She was alive, feeling all the pain and scrutiny up until her final day. “…eyelids became wet with blood, while whites of her eyes turned ruby red and swelled out…” (42). “…will develop pattern of shallow, almost imperceptible breaths, followed by a deep intake and exhalation, then more shallow breaths” (43). -She felt as if she couldn’t breathe, smallpox seems to torture people to death. Smallpox Victim #3: Father Kunibert, lived. Priests have many times been around death beds to offer communions and put the mourning families at ease. Smallpox victim #4: Rialitsa Meschede, 5 yrs old, lived. She was located across the hall from Los at the time she obtained smallpox. This showed how contagious smallpox was. For someone could get it even if they never came in physical contact with the initial case of smallpox. Smallpox Victim #5: Magdalena Geise, nursing student Unlike many diseases that people can share rooms and not obtain from each other, smallpox was easily transferable. Geise had shared a room with Meschede, and whether she got smallpox before being in the room is unknown. “Most of the people who broke out with smallpox were patients and staff from 2nd and 3rd floors of St. Walberga hospital” (44). Key Players: Doctors Richter, Posch and Wehrle. These doctors traced the spread of smallpox, and concluded that many of the people either saw Los directly or caught it from people who came in contact with him. They had an expert come in with a smoke machine which let out smoke (similar to how this virus spreads) and they noticed that the smoke went outside of Los’s room and up the stairs. It also was able to get through closed doors by the cracks on the bottom. This experiment helped them realize exactly how people became infected. “To his amazement, the smoke came into the upper rooms from outside, having crept up the walls. Someone had contracted smallpox in each of those upper rooms”(46). “A biological wildfire had occurred in Los’s room…”(47). -80% of the people who contracted smallpox were on floors above Los’s. -average # of people who catch the disease from each infected person[R-Zero] is 3&20. (each person infected may give it to between 3 and 20 people) Key Players: 8 year old Bilkisunnessa, Bhola islander, reported the smallpox cases Without her, the virus could have spread even more, never to be eradicated. She was rewarded 62$. October 1977, Ali Maow maalin, broke out with the worlds final natural case of Variola, the plan was to vaccinate 57 thousand people around him, it worked. Flashback: Between ten thousand & three thousand years ago (How did it start!) At some point in time, smallpox had jumped from an animal into a human being. This was seen more recently with the HIV virus, when monkeys in Africa began spreading it to human beings (51). Viruses kill living things, which keeps the population in line and prevents overcrowding of a certain species. “Species become extinct, viruses move on” (51). “Viruses are nature’s crowd control…” (53). “The virus’s genes suggest that it was once a rodent virus” (54). OR “…host of smallpox may have been an African squirrel” (54). INSECT NEWTHUMAN (Possibility) Epidemiologists suggest that the smallpox virus needs a population of 200,000 people living within 14 days of travel from one another in order for the virus to keep going (53). -At around 1000 B.C, city states in Southeast Asia started attracting more people and the populations increased. This could have been the time where it started to effect people. Although, researchers are not sure what time smallpox began to affect people it seems to have rooted itself around China or Southeast Asia. Smallpox: (could not spread to Japan, the population was too thin to be effective. 55) ChinaAncient Japan Korea Ancient Japan In 1520, Captain Panfilo de Naravaez landed on the east coast of what is now Mexico” (55). -He had a slave present who had the virus of smallpox, this one slave spread it and almost half of Mexico fell victim and died. (55). Since Smallpox is such a devastating, fast acting disease it killed off many people in the early Americas. The Europeans who came to settle and trade in America seemed to use it as a bio warfare tactic amongst the Indian tribes. “Out of regard for 2 visiting chiefs we gave them blankets and a handkerchief out of the smallpox hospital. I hope it will have the desired effect” (56). Key Players: Blanket Baba, guru and Brilliant, follower This guru believed that eradicating smallpox was his and his country’s duty. Brilliant and his program made 2 billion house calls in India to fight smallpox. India had a large population and as people traveled so did smallpox. The fact that many people used the train as transportation correlated with the amount of smallpox cases that spread. With Brilliants advice and his perseverance he was able to be heard, he was able to close transportation ports such as the trains, buses and airport (69). Another issue was Mother Nature, in 1974 a Monsoon caused severe floods in Bangladesh which left people to settle in out of town slums, carrying smallpox as they fled. “Women were handing me their babies. The babies were already dead. I heard rumors of birds carrying torn-off limbs of small children” (68). “By 1974, smallpox was nearly gone from Asia” (70). In 1978, a medical photographer named Janet Parker contracted smallpox at her home in England. She contracted the disease from particles that had escaped during research at the nearby University This case illustrated the rationale behind the WHO asking, in 1976, that all laboratories cease experiments on smallpox and send their samples to one of the two “Collaborating Centers:” The CDC and a research institute in Russia, formerly Smallpox is confined in a locked freezer in a secret location in a Level 4 biological containment zone: in the United States, at least In 1989, a scientist named Vladimir Pasechnik defected from the Soviet Union, where he claimed he had been involved in a bioweapon development program known as the Biopreparat He claimed that the Soviet government held massive stocks of frozen plague and smallpox which had been genetically engineered as a viable biological weapon In 1990, the Soviets launched a test ICBM containing a MIRV (multiple independent reentry vehicle) which did unusual things like give off heat (as if it were a refrigeration unit) and utilize parachutes to orient its payloads upright. In 1991 a British-American security team was granted access to inspect certain scientific facilities in Russia to check for evidence of bioweapon development The found suspicious technologies and were given conflicting accounts by Russian scientists. For example: At a virological research institute known as Vector, a technician informed them that the facility was working with live smallpox, but this was later denied by a head scientist at the same facility. More recent intelligence has only confirmed more evidence of an active and dangerous Russian bioweapons program which includes engineering and producing weaponized smallpox: A foreign team touring Vector in 1999 discovered a bioreactor which seemed to be designed to amplify stocks of smallpox, a theory corroborated by previous intelligence. Scientists there maintained that it was a sewage-treatment tank. “Today, both the Zagorsk Virological Center and the bioweapon facility at Pokrov are under extremely tight military security. Both sites are controlled by the Russian Ministry of Defense. They are closed to all outside observers and have never been visited by bioweapons inspectors… ‘When we approach people in those places,’ Alan Zelicoff said, ‘The door is literally slammed in our faces. We are told to go away. I think the conclusion is that they are going ahead with biowarfare.’” – p.116 The microbiologist Richard Spertzel led a United Nations biological weapon inspection team in Iraq between 1994 and 1998 In an abandoned warehouse on the Habaniya airbase outside Baghdad, the team found a machine designed to freeze-dry seed socks of virus. It was labeled “SMALLPOX.” An outbreak occurred in Iran/Iraq in 1972 which was around the time when Iraq began its biological weapons program. “It is inconceivable to me that at just the time when they were starting a biowarfare program they would have gone around Iraw and thrown out all their smallpox.” –p.118 Dr. Hazem Ali, a virologist who ran the Iraqi weapon development facility known as Al Manal was questioned by UN representatives in 1995: He claimed that the facility was working to develop camelpox as a biological weapon According to Spertzel, there is no conceivable way that camelpox could ever infect a human being and no reason any halfway intelligent scientist would consider it reasonable to attempt developing a weapon with such a virus His conclusion was that this story was a cover for research using actual smallpox. Reactions There is ongoing controversy over the best way to handle the clear biological threat posed by the smallpox virus Some considerations: If no nation or organization currently has stocks of variola, keeping seed stocks of the virus (even under heavy security) poses only a threat, should the stocks ever fall into the wrong hands It however seems very likely that unofficial repositories of smallpox exist If this is the case, destroying the stocks at the CDC and in Russia might only weaken any potential for researchers to develop a defense against weaponized smallpox To this end, the vaccinia inoculation is impotent because: Smallpox could be genetically engineered to be resistant to the vaccinia inoculation Moreover, vaccinia is an unacceptable risk in the pregnant and immunosuppressed, leaving this population vulnerable in case of attack On the other hand, the potential of using these stocks to develop a reasonably safe vaccine or countermeasure is debatable, considering that smallpox only infects human beings – how would we ever test a new vaccine? Recent developments In 1990 the WHO formed a committee which unanimously approved the decision to destroy the repositories of variola In 1991 scientists decoded the DNA of a certain strain of smallpox so that some research could continue even without the live virus June of 1995 was set as the official “date of execution” Abruptly the US Department of Defense rejected the proposal and the deadline passed Opposing viewpoints from The Demon in the Freeer Peter Jahrling, the senior scientist at USAMRIID, is adamant that our stocks of variola not be destroyed: “If the world wanted to have a new vaccine or an antiviral drug for smallpox, then the virus would need to be kept for scientific experiments… researchers could use that time to see if it would be possible to cure smallpox with a drug or if it would be possible to find an animal that could be infected with smallpox so that new vaccines could be tested.” –p. 133 Donald Henderson is a staunch advocate of destroying all stocks of the virus: “He thought than an antiviral drug for smallpox was a long shot that would waste resources… ‘To get a new drug for smallpox will cost three hundred million dollars, and the money simply isn’t there,” –p. 130 WHAT TO DO?