The recent, ongoing controversy about genetic experimentation with pathogens of high potential consequence for global health raises serious questions about our global capability and capacity to 1) detect events associated with accidents of biological technology ("biotechnology"); 2) recognize those signatures; and 3) issue timely warning of such phenomenon to the world in a transparent process free of political tendencies to withold information.
First, please refer to prior posts on the difference between signature detection, recognition, and warning. Here we define capability as the inherent knowledge of how to execute the analytic discipline of biological signature detection, recognition, and warning; and capacity as the global load factor for capability, where obviously a single analyst cannot possibly watch the entire planet.
In regards to the recent reports of deliberate genetic experimentation with H5N1 virus, the root question that should have been asked by the media and anyone astutely watching the controversy is why did the US National Institutes of Health (NIH) authorize the expenditure of US taxpayer funds for the experiment in the first place?
Funding from NIH does not happen magically. One has to respond to a Request For Proposals (RFP) with a formal proposal that includes a detailed description of the experiment that is to take place and the justification for that experiment. There is a rather uncomfortable question to be asked of Dr. Fauci and his staff that goes something like this: "Were you aware of the nature of the experiments about to be conducted by these researchers using US taxpayer funds before the experiments were actually executed?"
However unlikely, it is a well-documented fact that the more infectious an agent, the more likely it is to infect laboratory workers. In this particular case, the probability for an infection to occur was likely neglible, but there nonetheless. And trust that the world's public will not accept any excuse should the unthinkable have happened: a laboratory accident that triggered a community outbreak. The terrible juxtaposition of the highly improbable with the unthinkable consequence again raises its head.
So let's play this scenario out: what is the global capability and capacity to pick up on these kinds of events? This question is asked because, if we are to believe then the NIH failed to recognize the risk in conducting these experiments in the first place, then how fast do we honestly think we as a global community would have recognized the "oops" should the virus have infected one of the laboratory workers... a worker that went home that night to expose others? How many chains of transmission would have occurred before it would have been picked up by an astute physician or public health analyst? How fast would the dots have been connected to trace back to this being an engineered H5N1? How fast would seed stock have been secured for vaccine production companies? How fast would those companies be able to grow vaccine stock and execute distribution?
The answers are very, very bad and uncomfortable. Let's give some additional data points:
1. The discovery of Marburg virus in Germany, 1967. This was a laboratory accident involving a previously unknown lethal, transmissible virus. Exposed laboratory personnel went home to their families and in turn exposed them. Note the initial diagnostic confusion, calling the disease "yellow fever", then "monkey disease":
Aug 23, 1967 Sept 13, 1967
2. Laboratory Accident Historical Surveys
It is useful to review the historical records of laboratory accidents. Figure 1 displays the top diseases and pathogens that infected and killed laboratory workers in the United States from 1930 to 1950, the results of the most comprehensive survey of its kind, conducted by Sulkin and Pike in 1951.
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Figure 1. Laboratory infections [a] and case fatality rates [b] by agent / disease for civilian laboratories in the United States from 1930 to 1950. This is a sampling of the original data. The entry titled “encephalitis” refers to infections by Western (1), Eastern (1), and Venezuelan (11) equine encephalitis viruses and Russian Far East encephalitis virus (1). Infections were due to other pathogens as well.
Figure 1 represents a sampling of the total list of agents involved in reported laboratory infections. Other agents and diseases included:
- actinomycosis
- ascariasis
- B virus
- blastomycosis
- dengue
- giardiasis
- glanders
- gonorrhea
- hookworm
- influenza
- leishmaniasis
- leptospirosis
- louping ill
- measles
- meningococcal meningitis
- mumps
- non-typhoidal salmonella
- Pasturella species
- pinworm
- plague
- ringworm (Candida)
- Rocky Mountain spotted fever
- schistosomiasis
- Serratia marcescens
- sporotrichosis
- Streptococcus pneumoniae
- strongyloidiasis
- syphilis
- tetanus
- vaccinia
- vesicular stomatitis
- viral diarrhea
All manner of infectious agents and their byproducts such as toxins have essentially posed risk for laboratory workers not protected by Biological Safety Cabinets, negative pressure rooms, proper handling protocols, or vaccine. During the time period covered by the survey, there were few vaccines or antibiotics to mitigate exposure. It is believed the survey was a gross underestimate of the true number of infections. There was no systematic reporting mechanism to report laboratory infections in the United States at the time, as is the case now.
Singh provided an updated perspective based on Pike’s survey in 1976, as shown in Figure 2.
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Figure 2. Laboratory infections [a] and case fatality rates [b] by agent / disease for civilian laboratories in the United States based on updated assessments by Pike in 1976. This is a sampling of the original data.
When considering biological weapons programs, new hazards were introduced relating to handling of aerosols, mass production, and deployment testing of live agents. Figure 3 provides summaries of laboratory infections in Fort Detrick personnel during the years of the active United States biological weapons program (1943-69).
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Figure 3. Laboratory infections during the years of the active American biological weapons program (1943-1969), showing annual infections due to anthrax [a], tularemia [b], brucellosis [c], Q fever [d], and Venezuelan equine encephalitis [e]. In the case of Venezuelan equine encephalitis, an ineffective live attenuated vaccine candidate was responsible for a number of infections. Use of Biological Safety Cabinets began in 1950. Anthrax vaccine was available beginning in 1952. Tularemia vaccine was available beginning in 1958. Brucellosis research was decreased beginning in 1953; no vaccine was available. A vaccine for Q fever was available in 1965. The TC-83 live attenuated Venezuelan equine encephalitis vaccine was available in 1963.
Other agents and diseases were responsible for laboratory infections at Fort Detrick such as:
- plague (pneumonic)
- glanders
- psittacosis
- botulinum toxin
- staphylococcal enterotoxin B
Aside from the obvious increased risk for a laboratory accident being related to handling live agents, there are several risk characteristics worth noting:
- the infectious agent:
- causes clinically significant disease in humans
- is considered a disease of public health significance (especially from an international perspective)
- is associated with a low infectious dose
- transmits efficiently from person to person
- there is no or minimal availability of vaccine, antibiotic, or other effective medical countermeasure
- the laboratory environment:
- produces or works with aerosols
- does not utilize Biological Safety Cabinets, negative pressure rooms, hazard suits for personnel, or other protective mechanisms
- has laboratory workers unfamiliar with proper handling protocols for the agent in question
3. The epizootic of Venezuelan Equine Encephalitis in Venezuela and Colombia, 1995. This was a significantly disruptive epidemic involving an estimated 100,000 people that peaked at the same time as a seasonal peak in direct, non-stop air traffic to Florida in 1995. This was yet another example of warning failure due to failure to detect, recognize, and warn. Most poignant was the hypothesis the epizootic was due to a laboratory accident- a hypothesis posed only years after the fact.
Download Blake et al VEE in 1995
4. The accidental distribution of influenza A/H2N2 sample panels:
CAP, the American Association of Bioanalysts, the American College of Family Physicians and the American College of Physician Services all sent proficiency testing surveys containing one or more samples of A/H2N2 to approximately 6,500 labs in the United States. Proficiency testing panels containing A/H2N2 samples were also sent to laboratories in Belgium, Bermuda, Brazil, Canada, Chile, France, Germany, Hong Kong, Israel, Italy, Japan, Lebanon, Mexico, Saudi Arabia, Singapore, South Korea and Taiwan. The World Health Organization has informed the Ministries of Health in these countries.
5. The still-open case of possible ongoing transmission of polio vaccine-derived virus type 1 in Haiti. Here translocation of a suspect case to North Carolina went completely undetected by North Carolina's public health officials, CDC, and PAHO/WHO. The context of social outcry over the suspected accidental introduction of cholera by the United Nations to Haiti provided a strong disincentive for officials to carry out a complete investigation. The still-open question is whether deployment of Sabin / oral live attenuated polio vaccine in Haiti resulted in the escape of what may be, in essence, an accident of biotechnology out in Haiti's ecosystem continuing to recombine with native enteroviruses. The lack of a credible investigation into this question remains a concerning point of accountability for PAHO and CDC. Even more concerning is the multi-million dollar industry interest in continuing to produce, distribute, and vaccine people in extremely vulnerable areas of the world with this agent that has a well-documented nasty habit of causing transmissible disease.
These of course are but some of many examples and observations related to the concern of the proliferation of biological technology. Accidents should be expected as human-driven processes and procedures are fallable by nature. And politics certainly have, do, and will cloud situational awareness.
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