Smallpox

•Smallpox was once prevalent throughout the world, existing as an endemic infection wherever the population was sufficient to sustain transmission

•Outbreaks of “Variola” approximately 30% mortality. Survivors had distinctive residual facial pockmarks•Sometimes blindness•Described in USA by Chapin in 1897•Smallpox has no animal reservoir, and no human carrier state, so it must spread continuously in order to survive

A prevalent disease

•Of all the “pestilent diseases” smallpox is the most lethal•US stopped vaccination in 1972, and most of the world by 1983•This means that a huge % of the current global population has never been vaccinated, or immunity has long waned

We old folk are okay…….

•Genus: Orthopoxvirus

•Family: Poxviridae [includes monkeypox, cowpox, camelpox]•Largest genome of all viruses; ovoid brick-shaped structure consisting of dsDNA (unlike most others, the DNA is replicated in the host cell cytoplasm)•Virus gets implanted in the respiratory mucosa, drains to the regional lymph nodes, followed by viremia•Virus picked up by leukocytes, which then get jammed in blood vessels in the dermis, infects local cells, causes the pustules.•Pustules are highly infectious•Patient generates an antibody response. The role of CMI not known [although there is good CMI to cowpox]

The virus

•Smallpox is caused by two very closely related virions

•Variola major, variola minor, distinguished only by PCR

•Gets implanted on the respiratory mucosa

•7-17 day incubation period

•High fever within a few days, headache, backache

•Gradual development of maculopapular rash, results in dermal pustules

•Death caused by overwhelming viremia

Disease progression

Facial pocks highly charcteristic of individuals who survive smallpox

Mozart had himself painted “as is”.. .George Washington got “airbrushed”*, as did Stalin

Positive: servants, nurses, etc, who had smallpox scars got hired because they had survived and wouldn’t bring the disease in

* Washington is thought to have caught smallpox in Barbados in 1751 [he was an avid diarist and entries are missing for a 24-day period here…]

You’ve had smallpox, haven’t you mate?

•Killed millions•Helped the Conquistadores•Made people obey the Scriptures•Brought us the science of vaccination•“Curse of boils” Timothy 6:1-2, Exodus 9:8-11•Persia, Rhazes (865-925) “Treatise on smallpox” – 910, thought we are all born with latent diseases and disease was an attempt to expel these•American Indians . . “The rotting face”

The Angel of Death

•Appeared during early agricultural settlements, approximately 10,000 BC•Egyptian mummys approximately 1500 – 1100 BC, including Ramses V had evidence of disease•First written records – perhaps…China 4C AD•Spread initially into northeast Africa – India by traders•Outbreak in Athens in 430-BC described by Thucydides•Term “variola” arose in 6C AD - Latin…varus – pimple•10C onwards in Anglo-Saxon – pocca, pockes, pokkes•Emergence of the term “small pokes”, the great pokes was syphilis•Introduction of smallpox into Western Hemisphere in early 16th C•Decimated the Ameri-Indians – Aztecs, Incans•Impact on society was profound•Emergence of “deities” to smallpox arose•Danish ship took smallpox to Iceland in 1241 --40% of population killed (~20,000)•By18th C – 400,000 deaths/year in Europe, including 5 monarchs Hapsburg Iine shifted 4 times in 4 generations

Where did it come from?

•Shapona (W. Africa)•Shitala Mata (Hindus)•Chu’an Hsing Hua Chieh (China)

Gods of smallpox…..

•Oct. 26, 1977, last case seen in Somalia, but…..

•Civil war•Famine•No money•Not enough vaccine•Cultural beliefs, etc

•Lab accident – 1978- Birmingham

Bumps in the road

•1541 – African slave on a Conquistadores ship – part of a force led by Panfilode Narvaez sent to prevent Cortez from establishing a monopoly-- arrived in Mexico --Killed 90% of the Aztecs (>20MM people •With few Aztecs left alive, Cortez gave thanks to God for being able to claim yet another country for Spain and Christianity•When Pizarro reached the Incas of Peru in 1532 many had already died from smallpox•Without the spread of smallpox, neither Pizarro or Cortez, who had only small armies, would have stood a chance against the Aztec or Inca armies

God just doesn’t like you guys…..

•Doctors and quacks – smallpox provided a steady income!• Neither knew what they were doing !!•1700’s Thomas Sydenham (Brit) – “miasma” theory --versus Boerhaave (Holland) – “contagion”

Those nasty miasmas

Two members of the Royal Society – Mead and Woodward1719 – Meade treated with purges, Woodward with enemas

Defended their view points in a sword duel (both survived) Meade the better swordsman – offered Woodward mercyWoodward replied he feared Meade’s “physic” more than his blade!-it was noted at the time that wealthy people, who could afford Doctors, had much higher rate of mortality than poor people who could not

I will have satisfaction Sir!

•“Red” assisted healing – red shawls, toys in Japan •20 yds of red flannel used to wrap Joseph-I of Austria as he died in 1711•“Red light therapy” in the early 1900’s (and still today!)•Fever washes the blood!•Led to idea that bleeding would reduce fever –cutting, or using leeches• -useless, dangerous, but trusted by doctors and patients•Hubert Boens (Belgium) 1884 – anti-vaccine, promoted anal leech therapy!•Sydenham – 12 bottles of beer a day!

Quackery

•“Variolation”….deliberate inoculation with dried smallpox pustules in hope of contracting milder disease [then life-long immunity]….seems to have arisen in India and spread to China•From there – via trading routes into Europe and eventually North America

Variolation [“scarification”]

•Emanuel Timoni [Greek], trained in Padua and Oxford --made Fellow of Royal Society in 1703•1695 – 1703 attending physician at British Embassy, Constantinople•Had letter published by Royal Society in 1713 --Observed “healthy boys” with mild smallpox as donors then the recipient variolated•Over 7 yrs he observed this continually, and it seemed to work•Timoni’s letter had little impact•He had his own daughter inoculated in 1717•Problem could have been Royal Society journal (‘Transactions”) itself since it had some important papers mixed in with piles of total rubbish•Plus: the near-miraculous claims for varolation may have prevented it being taken seriously•Plus: this arose from ‘illiterate and unthinking Turks” and the Chinese-- uncivilized heathens versus the sophisticates of London•And this would have cut into the piles of cash doctors were getting “treating smallpox”

Dr Timoni

•“Variolation” is the deliberate infection of a healthy subject with smallpox to induce ‘immunity’ -i.e.hope you would get a mild disease rather than a fatal one •First described in S. Wales in 1720’s but in folklore going back to early 1600’s•Pustules cut off and dried, then rubbed onto hands of healthy people into scratches made by needles•In most cases, allegedly, only a very mild disease then occurred, plus the individual protected from there on•Articles describing these ‘techniques’ appeared in March 1723 issue of the Royal Society’s journal•The Royal Society however continued to ignore this, still depending on hot fires, leeches, and red flannel!•“a huge affront to common sense”•Records in 15C China of varolation or ‘nasal insufflation’ blowing powdered scabs up the nose--“mild smallpox cases selected as donor” The blowpipe had to be silver, right nostril for boys, left for girls•Two letters sent to Royal Society in early 1700 by a British trader who saw this performed in China (but the Royal Society never published them)

“Buying the smallpox”

•Enter. . . . Lady Montagu•Born 1689 Lady Mary Pierrepoint•“Beautiful, terrifying, intelligent, brilliant conversationalist and correspondent”•“…being a girl, she was naturally denied any formal education” ….but read all the books in her father’s library in Thoresby Hall (near Sherwood Forest)

Lady centerfold

Dad wanted her to marry Clotworthy Skeffington (Viscount Massereene in N. Ireland) but she was having an affair with Edward Montagu who was trying to become a member of ParliamentShe crept out of her room on Aug. 18, 1712 when she was 24 and met Montagu in an inn on the road to Dover. She fell ill and went to bed, Montagu was really nervous, had second thoughts, and went back to London! He came back, and they married on 23rd of August. The marriage was mostly a sham – despite her beauty Montagu was mostly disinterested, in both her and his new son. Her brother William stayed with her, for support, but got smallpox and died on July 1, 1713.

•Things turned around in early 1715, Montagu became an MP and they moved to London – he got a further job in the Treasury.•She assimilated into High Society, and also become an accomplished writer•Mid-Dec 1715, she fell ill, with symptoms of smallpox•She came close to death, but 3 weeks later recovered -however, her legendary beauty had been destroyed•In 1716 Montagu was appointed Ambassador to the Ottoman Empire (now Turkey) – His initial brief to stop the Ottoman/Austrian war•Timoni was still there, and Mary brought her own doctor – Charles Maitland•For the next 3 yrs she threw herself into Turkish culture – learning the language, dressing local, going to the markets, etc.•-she also noted that many of her local acquaintances did not have smallpox scars.•-describing inoculation she noted (in a 1717 letter to a friend back in UK) that the locals even “make parties for this purpose”•“The children . . . play together all the rest of the day” Then the fever begins to seize them, and they keep their bed two days, very seldom three . . . their faces never mark . . .and in eight days they are as well as before . . .”

•This letter also contains the statement that UK doctors would never “destroy such a considerable branch of their revenue for the good of mankind”•On March-18, 1718 – when Dad was away—her son Edward Montagu was inoculated by one of Constantinople’s “most experienced old women”-he went thru the symptoms but quickly recovered•Even though Montagu successfully negotiated the Peace Treaty of July 1718, he fell out of favor in London and was recalled•Lady Mary returned to society, and became friends with Caroline, Princess of Wales•In 1721 there was another smallpox epidemic, and that April Maitland inoculated her daughter Mary, in the presence of several prominent physicians.•This spread rapidly through High Society (Lady-M was a fabulous “networker”)

•With help from Princess Caroline, Lady Montagu got permission for the first ever “clinical trial”•-Six prisoners from London’s notorious Newgate Prison got inoculated – they all got brief symptoms only• -one, 19yr Elizabeth Harrison, got sent to nurse a boy with active smallpox, including sharing his bed. She never caught it.•On April – 17, 1722 Maitland was summoned to the Palace and inoculated the two daughters of Princess Caroline.•They both did fine.

•By mid-1700’s inoculation was the rage, and London was the epicenter•“risk to others” was the Achilles Heel, i.e. when you were variolated, you kept others at a safe distance for a week or so – if not they were at risk of disease “collateral cases”•Lady Montagu died of breast cancer in 1761, at the age of 73•Her daughter Mary married Lord Bute, who became PM•Variolation hung on longer than it deserved – vaccination should have replaced it faster, but the same “anti” arguments persisted, piled on with the ‘bestiality’ claim of cowpox

•“ . . . vaccination was discovered . . not in the intellectual power houses of the Royal Society . . . but in the quiet backwaters of Gloucestershire . . .renowned for its gentle green landscape and the quality of its cheeses . . . .”•A local apothecary, John Fewster, had gone to the London Medical Society in 1765 to report his observation that exposure to cowpox seemed to prevent smallpox – 30 years before Jenner•When Jenner’s paper was published in 1798, several others pointed out this was well known, but not widely reported, because it was ‘unverified or inconsequential’…“it was common knowledge to all doctors in the country”

•Jesty . . . “no attempt to publish or broadcast his results”•His experiment noted by Rev Andrew Bell in 1801, who argued that he had discovered cowpox vaccination, before Jenner

The cheese is damn good too…

Exposure to cowpox increasing resistance to smallpox known for years in rural England, but ignored by the doctors/quacks in London.

Dorset farmer, Benjamin Jesty, in 1774 took cowpox from a cow and vaccinated his wife and daughters [finally recognized by the Vaccine Institute in 1805].

This was two decades before Jenner, but Jesty never advertized his observations [plus the local clergy very upset with him for injecting his family]

Old farmer Jesty

Edward Jenner was born May 17th, 1749, orphaned at 5.

Sent to boarding school, where he was purged, bled, then scarified with dried smallpox pustules. He barely survived.

He became interested in medicine as a result, but did not learn Latin or Greek, so could not apply to Medical School

At 13, went to work with a country surgeon [Ludlow] which was probably where he first heard the milkmaid/cowpox story.

Then moved to St George’s Hospital in London, training under the great John Hunter. Jenner was polite, kind, considerate. Hunter was nasty, dominating, arrogant. Despite this, they became great friends.

By this time Jenner had inherited lots of land. He returned home, set up a flourishing practice, became interested in lots of other things [music, art, chemistry, ornithology, he even built a hot air balloon].

Edward Jenner

In 1795 he took a cowpox blister from Sarah Nelmes, a local milkmaid. [She caught it from her cow, Blossom]

He inoculated this into a 8-year old farm boy, James Phipps. Two months later, he variolated James with smallpox. The boy showed no symptoms of smallpox at all.

He wrote a paper to the Royal Society, but they rejected it [“n=1”]

He published his result privately instead, and it became widely read. Jane Austin was at a dinner where it was read to the guests…

Detractors:

Pearson, stole idea and set up a Vaccine-Pock Institute

Woodville questioned the safety

Rowley, the vaccine would “turn you into a cow”

Jenner had brought in a brilliant tutor to help his son, but the tutor contracted TB and gave it to both son and his wife.

Jenner was broke, depressed, and relied on “opium and brandy”

Friends rallied around, and Parliament gave him PS20,000

Things got better, the Royal College recommended vaccination rather than variolation, and Oxford gave him a Honorary Degree in Medicine.

At 71 he wrote a paper on bird migration considered a masterpiece

He had a stroke in August 1820. He survived, but had a seizure in the early hours January 26th 1823, which killed him.

James Phipps was a pallbearer

George Pearson – jealous of Jenner – pushed the “Jesty discovered vaccination” story – so that Jenner would not be funded by the government – but he only figured out Jesty’s exact identity after the money had already been awarded. Pearson finally got Jesty to London, and he was feted, but it had little effect.On Oct-16,1793, during a ferocious argument with colleagues about student admissions at St. George’s Hospital, Hunter collapsed and died (he was 65)Jenner was 19 when he first talked to a local milkmaid, 47 when he did his first vaccination, and 49 when he published itThere were lots of holes in his ‘Inquiry’ plus he was a convivial man, living nicely in rural Gloucestershire --he was now up against far cleverer, harder working, meticulous scientists – so he was easy meatPlus, if he was right, this would put variolaters out of business and moneyAfter the “inquiry” the term ‘vaccine’ soon came into general use, and in 1803 Richard Dunning (a Plymouth surgeon) first used the term ”vaccination”

The nice Dr Pearson

•“The Balmis Expedition” of 1803 -- three frigates left La Coruna on Nov- 20,1803 (main ship was “Maria Pita” with 22 orphaned boys – as providers of lymph containing cowpox) For 3 yrs, circumnavigated the world (~50,000 miles traveled)•Split into 3 routes, all over the world vaccinating as many as they could at each stop “arm to arm” and “arm to cow”•Projected image that Spain “really cared about its colonies”•In Peru, other Spanish travelers had already brought this•In Lima, a cartel of Doctors were already doing it, making lots of money, and as a result very highly hostile!•“a partial recompense for thesmallpox the Spanish had introduced”

The cowpox cruise line

Late 1800’s “mobile vaccination centers”i.e. “vaccination cows” (usually young Heifer less than 1 yr old, because bovine TB unlikely at that age)One person that tried to block Jenner (other than Pearson) was John Birch (a London surgeon who hated vaccination) “it could undermine the valuable role that smallpox played in killing off the children of the lowest classes as a merciful provision . . to lessen the burden of a poor man’s family. .”

Cow clinic

•Enthusiasm waned in 19C – harder to find cowpox plus some arm-to- arm “vaccinations” also transmitted syphilis, and leprosy!•“Anti-vaccine” societies didn’t like it, and objected to any mandate•Italians kept calves injected as a source in mid 1800s•Most of Europe did not become free of smallpox until ~1920•Continued unabated in other regions•-cowpox was used in Africa, but the virus quickly die in the tropical heat and was hard to preserve•Avirulent freeze dried virus invented by the French in 1920’s

Anybody got a poxy cow?

•Early 17C European settlers introduced smallpox to American Indians living along the Eastern seaboard•Earlier – French in Nova Scotia brought smallpox to the Algonquins in 1616•1632 smallpox killed off Indians around New Plymouth “just and appropriate intervention by God” in view of the settlers•Increase Mather and his son Cotton Mather Puritan reverends in Boston saw it as genocide of these “pernicious creatures”

Into America

•Cotton Mather was a key figure in the Salem witch trials where he was an enthusiastic inquisitor and torturer•(29 convicted, 19 hanged, one crushed, five died in prison)•-he was convinced Satan lived in New England•-he had interest in medicine (even though he understood nothing, he read the RS Transactions, and had heard of slaves coming into US that had been scarified

Burn the witches

•On April – 21, 1721 a British warship (Seahorse) sailed into Boston – 2 sailors had early signs of smallpox•10% of Boston fled•Mather suggested inoculation, but this upset Boston’s powerful cabal of doctors – who reacted furiously•Just one Doctor (trained at Oxford) Zabdiel Boylston (FRS 1726) sided with Mather, and they started inoculations using Timoni’s method.•-all got nasty – Boylston attacked in the street. Mather had a grenade thrown thru his window•-when all the dust settled, in 1722, there was a mortality rate of 15% in Boston, but only 2% in people inoculated.

Boston bother

Settlers quickly understood the usefulness of quarantineCoasters Harbor Island off Rhode Island, Sullivan’s Island off S. Carolina“Inoculation centers” began to become set up, spreading from New England to Virginia, often with opposition from locals especially the clergy1747 City Ordinance in NYC outlawing the practice.-but elsewhere – further inland the practice became common-plus many of the settlers came from Europe and had had smallpox as children – so there was lots of “herd immunity” to start with, and contagion was less fearedAs the practice increased, so did the cost --often 2-3 pounds (~100$ these days) so poor people could often not afford it--these disproportionally died in epidemics-a rich person might get inoculated – get disease then give it to unprotected servants….“Working class risk”“Sutton protocol” 1760’s Robert Sutton dispensed with rituals, purging, etc. used v. shallow wounds and got pustules from fellow vaccines rather than from naturally infected donors --Probably involved virions of reduced virulence but just as immunogenic

Further into America…..

•Continental soldiers of the Revolutionary War --usually came from rural areas – volunteers expecting short terms of duty•1775 Siege of Boston – Americans had driven the British army back within the city--Volunteer soldiers surrounded the city only to fall prey of smallpox•Washington had to decide between inoculating his army or exercising stringent prevention--keeping suspect cases away from the American lines•Problems increased: patriots in Boston wanted to leave the city •Food became short•As things became grim in Nov 1775 the British General Sir William Howe had his troops inoculated. Howe also allowed “selected Bostonians” to leave, thinking they would carry smallpox to the surrounding Americans•In March 1776 Howe surrendered, left for Nova Scotia but smallpox remained and continued to sweep Boston•Inoculation rates went through the roof – Harvard demanded it •One of many examples at the time of how disease had centrally impacted military fortunes/outcomes

“Rage militaire”

•Late 1775 the American army converged on Quebec led by Generals Benedict Arnold and Richard Montgomery

America invades Canada

•Montgomery attacked on 12/31/1775 and was almost immediately killed (shot in head by grapeshot)•Some soldiers breached the city walls but were captured—once in prison, smallpox spread rapidly•Officers (mostly from families that inoculated) survived•Foot soldiers (most rural, no immunity) died en masse•British re-inforcements arrived via the St. Lawrence River on May 6•The Americans, decimated by smallpox, fled•Those that survived had been inoculated (pins under finger nails) --despite the risk of court martial•The relieving general also banned it, then almost immediately died of smallpox!•Same events Southwest in Montreal – the British, with local Indians, attacked the city in May, and the Americans, many of whom had smallpox, could not defend it•British continued policy of inoculation of any of their troops who had not had smallpox, so had no problems

As the Revolutionary War took shape, George Washington was worried the British would deliberately try to spread smallpoxIn fact, they already had at Fort Pitt in 1763, giving two smallpox soaked blankets to the local Indians-Whether the Brits did so deliberately or not, this was posted as a cause at Boston, Quebec, and Virginia

Those bloody nasty bloody Brits….

•By 1776 the Continental Army was a shadow•Poor man’s army – jobless, landless, hired “for the duration”•Some were Mercenaries, hired by richer men to take their place•In return they got food and clothing, sometimes the promise of land plus wages – there was more than one occasion they refused to march without being paid

Pitiful army

•In Feb 1777 Washington relented and told President John Hancock (2nd Cont. Congress) he now favored inoculation – while there were many foreign born troops in his army, there were also many native-born who had little or no immunity. This posed a huge operational task for the army•Not only did this need to be done from Connecticut •right down the East Coast, because it would temporarily disable the vaccinee, the utmost secrecy was needed just in case the British took this opportunity to attack•June 18, 1778…the British army left Philadelphia and crossed the Delaware heading north •George Washington crossed in pursuit – his army no longer ravaged by smallpox and now in good condition•A few days later they squared off at the Battle of Monmouth- a draw

A huge reversal in policy [and why you don’t have a Queen]

•At the end of the 1779-81 the British occupied Charleston, and they promised freedom to the black slaves, many of whom fled to British protection•Unfortunately, most of these had no resistance to smallpox•Oct 1781 Cornwallis was besieged at Yorktown – The Americans inland, the French offshore•-despite the contribution of the blacks in defending the city, they were riddled with smallpox, and sent out of the city to die•-even the ruthless Hessian mercenaries were appalled•On Oct-19, the British surrendered (their army got drunk to celebrate)•“Negroes lay dying everywhere” in the liberated city

•“The newly acquired immunity of the Continental Army swayed the balance”

Screw the blacks, your Majesty

Isolated for thousands of years from plagues in the rest of the world – native Americans might have become genetically susceptible-also may have had less MHC diversityDespite this, outbreaks were sporadic – reflecting the huge size of the country, low population density, minimal transportation

No resistance, kemo savie

•Transport and trade into the American West•Sioux Indians traded for guns, and in the late 1600’s spread west from the Great Lakes into the Plains using these weapons (plus their innate ferociousness) to displace indigenous Pawnees, Omahas, and Arikaras•The displaced Arikaras soon themselves traded for guns--they were agriculturists with well organized stockades. These were crowded, and in came smallpox (source still unclear)•A major standoff along the Missouri River with the Sioux 1767-1768•1779-1783 Multiple outbreaks in multiple Indian tribes. Shoshones/Comanche trading also brought smallpox up from the south west•Despite romantic stories, native Americans did not often fight each other. But the guns and lots of ammo changed these dynamics, spreading destruction, and with it – disease

“The gun and the horse”

•Hudson Bay traders, Europeans and Cree Indians – vast network across Canada•Spanish missionaries –North Mexico and into New Mexico•Many other outbreaks as well in the interior – but “few there to see or record them”

Into the continent

•Northwest epidemic•Observed by British explorers among the Tlingit Alaskan Indians in 1787•Pockmarks seen on Indians Oregon/Washington/Puget Sound areas•Source unclear: Spanish and other traders? Russians? (well known to have spread smallpox across Siberia? By American Indians trading up the Columbia River?

The American North-West

•Massive impact on American Indians•“loss of generations of unrecoverable knowledge”•Households combined, alliances destroyed•Religious convictions altered or abandoned•Catastrophic pattern of population decline•Triple whammy of smallpox, war, and abandonment by the British•In the South West, smallpox depleted the ability of the Comanches to keep the Spanish at bay

Loss of a great culture

•Late 1940’s – large scale production of freeze dried vaccine•Through next 3 decades global effort to eradicate disease•Attempted to reach 80% of population in each country; plus set up systems to detect and contain outbreaks

Vaccinia vaccine

•Cowpox/Vaccinia Multiple strains, passage histories unclear

•Includes sheep + water buffalo in addition to cows!!•No “seed lot” until 1960!••After 1967 . . Lister strain in Europe, NY City Board of Health strain •ACAM 2000 (NYCBH) Acambis Boston, used as biodefense strain•1975 MVA Germany – high expression of recombinant genes plus replicative deficiency; used as carrier for other antigens [incld TB]•Can be used in people with immune suppression

•Big problem: how would you actually know if new attenuated strains have sufficient efficacy?•No new outbreaks…..No animal models…….No “surrogates of protection”

Cowpox vaccine

WHO announced that smallpox was eradicated on May 8, 1980

It soon became clear that Russian biowarfare experts still were working with smallpox and had manufacturing facilities capable of making smallpox in “the tons range” –also were capable of making recombinant weapons (big genome for a virus)….Cheney convinced President Bush Dr Germ in Iraq busy putting Ebola into smallpox.

Worry Soviets loading smallpox into their nuclear weapons. Huh?

Bioweapon?

•British forces in the French and Indian war (1754 – 1767) soldiers distributed smallpox–infected blankets to Indians

•WHO asked every country with smallpox samples to destroy them (they all “complied”!)…or transfer all stocks to the CDC in Atlanta, or the Viral Preparations Lab in Moscow. (The Soviets did so, but then moved these to their biowarfare center in Novosibirsk, Siberia) “VECTOR”

•It is still unclear what happened after collapse of Soviet Union; Scientists not paid . . . etc. Worry was Variola virus can be freeze dried, makes stable aerosol

•US made 300MM doses in 2002, now in Acambis fridge in Boston•CDC has mass vaccination plan

Bioweapon….continued

•Should we destroy all stocks of the virus?

•AG: Would halt any attempts to understand the pathogenesis of the virus

•AG: Would not guarantee “hidden stocks” would be destroyed or forgotten

•AG: Couldn’t develop anti-viral drug or more attenuated vaccines

•PRO: Unintentional release into a (now) susceptible global population would lead to serious outbreak

Should we keep the virus alive?