Pathogens are maintained in laboratories around the world for many reasons. They can be used to develop vaccines, to provide materials for diagnostic tests, or to study genomes, offering clues as to how pathogens may evolve so that we are better prepared to deal with them.

There is debate within the scientific community as to exactly what kinds of research should be done on especially nasty organisms commonly called Potential Pandemic Pathogens, such as the deadly SARS respiratory virus or highly pathogenic avian influenza viruses. Some believe the risks of escape, though small, are not worth taking as an accidental release could sicken or even kill millions of people, animals, or both.

While biosecurity has greatly improved in recent decades, the risk of pathogen escape from any laboratory is not zero. The potential harm caused by such an event must be considered alongside the potential benefits that can come from laboratory work.

For most pathogens – those that cause very low mortality rates and without the potential to spread rapidly around the world – the benefits probably outweigh the risks. Over time, billions of dollars and thousands of lives saved from the knowledge and products gained outweigh the occasional accidental release of these pathogens.

Laboratory escapes of harmful organisms occur despite the numerous measures to prevent them. Identifying them, recognizing their costs, and learning how they happened and how to handle them allow for a better informed debate on the subject

Escape Scenarios

There are several ways pathogens can exit a laboratory undetected by staff:

• Pathogens can leak out.

• Infected people, animals, or vectors such as mosquitoes can act as Trojan horses, taking pathogens from the lab with them.

• Pathogens can be removed on purpose by someone with malicious intent.

• In a few cases, the escape route remains a mystery.

Foot and mouth disease (FMD) is a highly contagious virus that can spread quickly, particularly in temperate climates, between cloven-hoofed animals including cattle, sheep, goats, and swine. It kills relatively few adult animals, but its victims have greatly reduced milk and meat production from which they rarely recover fully. Financial losses are heavy over time, including lost trade opportunities, so much research has gone into learning more about this pathogen in the laboratory.

FMD-free countries often deal with new outbreaks through a stamping out strategy, in which all affected and exposed animals are culled. In the 2001 FMD outbreak in the United Kingdom, this resulted in an estimated 10 million livestock deaths and billions of pounds in losses.

Because of these potential costs, an FMD virus escape from a laboratory, particularly one in an FMD-free country, is potentially devastating to the agriculture sector. In the US, work with live FMD virus is undertaken at the federal government’s Plum Island Animal Disease Center, located on a small island off the eastern tip of Long Island, New York.

In 1978, FMD erupted in a herd of cattle on Plum Island but outside the laboratory. 200 animals were euthanized but fortunately the virus did not escape the island. The cause was not pinpointed, but it occurred at the same time construction work was going on at the facility, which may have been a factor.

A similar event happened in the UK in 2007, when FMD was found in cattle located 4 km from the UK’s Institute for Animal Health (renamed the Pirbright Institute in 2013). The close proximity of the outbreak to the laboratory and the fact that the FMD virus strain was nearly identical to that of a strain used for vaccine development at the lab suggested the outbreak came from there.

Investigators believe the virus escaped the facility through a leaky pipe channeling lab waste to a nearby treatment plant. The mud created by the leak contaminated vehicles leaving the facility. Eight different farms experienced FMD outbreaks over a two-month period, costing an estimated 200 million UK pounds in control efforts, export restrictions, and lost production.

The most recent case of FMD escape from a lab may be in Russia’s Vladimirskaya region 160 km east of Moscow, where an FMD outbreak was announced in October 2016. The Arriah Federal Center for Animal Health, 1 of 3 laboratories making FMD vaccines in Russia, is located just 14 km from the farm where FMD was reported. Genotyping is underway at the time of writing to help identify the origin of this virus. Some 800 head of livestock were culled and tens of thousands of others received emergency vaccination to contain the outbreak.

Anthrax

Zoonotic pathogens pose more than just financial threats should they escape. One of the deadliest such events occurred in the city of Sverdlovsk (now renamed Yekaterinburg), 1400 km east of Moscow in the Ural Mountains of what was then the Soviet Union.

In March 1979, a reported 64 people died from either inhalation or ingestion of Bacillus anthracis, the bacteria that cause anthrax. 32 more became ill but lived. Initially reported by Soviet authorities as due to consumption of contaminated meat, revelations after the fall of the Soviet Union asserted that bacterial spores had escaped from Compound 19, a military biological research facility on the south side of Sverdlovsk city. A clogged air filter at the site had been removed and not immediately replaced. An alert employee quickly noticed the missing filter and had it replaced, and probably prevented many more deaths.

The majority of human anthrax deaths occurred within a narrow, straight geographic band about 4 km long, with Compound 19 at the northwestern extreme of the line connecting them. Six villages up to 50 km from Compound 19 lost sheep and cattle to anthrax during the same period, further away than the human cases but lying on the same NW-SE axis from Compound 19.

Winds from the northwest were rare in Sverdlovsk at the time, but a brief spell of northwesterly winds occurred on 2 April 1979, 2-3 days before the first appearance of human cases and in line with the disease outbreak axis. This was proposed as the most likely time the spores escaped the research facility and was a stroke of luck in that it carried the pathogen away from the heavily populated city center. See here for declassified documents on the Sverdlovsk anthrax outbreak.

The United States is not immune to the inadvertent escape of anthrax either. In June 2014, the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia reported that it had shipped anthrax bacteria samples that were supposed to have been killed to a different laboratory which was unequipped to handle live anthrax.

Not all of the bacteria, however, had been killed due to a lapse in protocols. 62 CDC employees were potentially exposed, all of whom were promptly treated or vaccinated for anthrax. Once again, the damage could have been worse had an alert employee not noticed bacterial growth in the sample when it should not have been there.

Theft

The theft of pathogens to use as bioterrorist agents is an even more concerning scenario. This may be what happened in September 2001 when letters filled with anthrax spores were mailed to prominent media personalities and politicians in the United States. Five people died and 17 others fell ill as a result.

Though questioned by many, including in the scientific community, a 9-year long Federal Bureau of Investigation inquiry concluded that a biologist at the US Army’s Fort Detrick, Maryland biodefense research laboratory produced the spores in the lab and mailed them out in order to spark renewed support for his work on developing a new anthrax vaccine.

Humans as Vectors for Escape

The worry that laboratory employees working with virulent organisms may become infected and spread the pathogen outside the lab before they know they are infected is significant. This is particularly true for the so-called Potential Pandemic Pathogens.

Smallpox, for example, eradicated by 1980, is known to have escaped in this manner from laboratories in the UK on at least 3 occasions. Even in the 1970s, vaccination of researchers was the principal form of protection and many of the biosecurity features of today’s labs were absent.

In 1978, a medical photographer in the anatomy department at the University of Birmingham Medical School in the UK contracted smallpox. Her office was located directly over the smallpox research area one floor below. The woman infected her mother, who survived, but the photographer ended up as the world’s last recorded smallpox victim. An investigation assumed that the virus likely traveled on air currents up a service duct into the photographer’s office.

Curiously, this latter case reminded some of another medical photographer in the same anatomy department who contracted a mild strain of smallpox 12 years earlier, in 1966. The photographer had numerous international friends and colleagues and was assumed to have acquired the disease from one of them. Some six dozen people around the city were likely infected directly or indirectly through the photographer, but all were mild cases. Re-examination of this outbreak 12 years later led to the conclusion that this photographer too was infected by virus making its way through the service duct.

Potential Pandemic Pathogens

Severe Acute Respiratory Syndrome (SARS) is another pathogen of concern for laboratories. This coronavirus infected over 8,000 people in more than 20 countries in 2003, killing 774 mainly through the pneumonia it causes. This virus has been carried inadvertently out of labs in East Asia by infected workers on at least five separate occasions. Fortunately, these cases were all contained before more than a handful of people became infected.

The year 1977 was very rare in that not one but two different strains of seasonal influenza A viruses circulated widely around the world. One of these, H1N1, was virtually identical genetically to the H1N1 virus prevalent in 1949-1950. Viruses like influenza, whose genetic information is stored as RNA (rather than DNA), are known for their rapid mutation rates. An influenza virus unchanged over 27 years is extremely unlikely – unless it has been frozen for that time, such as in a laboratory.

This may well be what happened in 1977. This re-emergent H1N1 virus is estimated to have infected up to 20% of the world’s population under 21 years of age, though usually with only mild symptoms. A large portion of the population older than 21 had been exposed to the virus in the 1940s-50s, so were immune.

The Future

As we have seen, mistakes will happen, even in the sophisticated laboratories where dangerous pathogens are studied. The escape of anthrax or foot-and-mouth disease for example, could cause great hardship but can ultimately be controlled.

This may not be the case with all pathogens. Researchers alter the genomes of many dangerous viruses in the laboratory to help them predict the effects of mutations in these rapidly-evolving organisms. In particular, work on SARS, Middle East Respiratory Syndrome virus (MERS), and highly pathogenic avian influenza viruses that have occasionally caused illness and death in people (H5N1 and H7N9) have sparked debate even in the scientific community.

Risk-benefit analysis for each organism to be studied will play an important part in the decision to proceed or not. The answers are not easy and compromises will certainly have to be made. But the debate so far appears to be a healthy one.

 

REFERENCES

Furmanski M. Threatened pandemics and laboratory escapes: Self-fulfilling prophecies. Bulletin of the Atomic Scientists. 2014 Mar.

Rozell DJ. Assessing and Managing the Risks of Potential Pandemic Pathogen Research. mBio. 2015 Jul; 6(4):e01075-15.

The House of Commons. (1980). Report of the Investigation into the Cause of the 1978 Birmingham Smallpox Occurrence. London: Her Majesty’s Stationery Office.

Warrick, J. (2010, Feb 20). FBI investigation of 2001 anthrax attacks concluded; US releases details. The Washington Post.

Henkel RD, Miller T, and Weyant RS. Monitoring Select Agent Theft, Loss and Release Reports in the United States-2004-2010. Applied Biosafety, 2012; 17(4): 171-180.