Biological agents are microscopic and invisible, and cannot be easily detected in small quantities without the use of sophisticated testing methods. This is one of the reasons why biological agents are feared – it is often after individuals become symptomatic (display symptoms and signs of illness) that testing is first attempted and in many cases a definitive test result may not be known until after an individual has recovered or died. Some diseases, such as smallpox, may have a distinctive clinical syndrome, which should raise high levels of suspicion, but diagnostic testing needs to be done to confirm the cause.
Recent advances in molecular biology, immunology and testing have given scientists and clinicians far better methods of detecting biological agents, even in minuscule quantities.
Three commonly used techniques for detecting and characterising biological agents are:
Culture, Microscopy and Sensitivity
Biological agents (except for toxins) are living organisms. This presents an opportunity to selectively grow a biological agent of interest (a process called culture) for further study and testing. Biological agent culture is a specialised process where organisms are placed onto media that selectively allow certain biological agents to grow. Once grown, an identified biological agent can be further studied by utilising various techniques for visualising them under magnification (using microscopes), and exploring their characteristics and vulnerabilities using sensitivity analyses. Culture, microscopy and sensitivity testing is a foundation technique for testing biological agents. Due to the requirement to grow the biological agent, this form of testing can take days to weeks to yield a result.
Biological agents can also be identified using specially designed and manufactured “chemical tags” that rely on protein molecules used in the immune system. The immune system contains molecules called antibodies that bind to, or recognise, very specific chemical and biological structures. This property of antibodies is exploited in order to create antibodies that create a visual signal (such as a colour change or other form of labelling) that identifies when specific binding occurs. A wide variety of tests are available that contain antibodies that specifically recognise certain biological agents, even high risk biological warfare agents, and produce a colour reaction that indicates the present of that agent in the sample tested. These kinds of tests are rapid, some producing results within minutes to hours.
Polymerase Chain Reaction
Polymerase Chain Reaction (or PCR) is the most recently developed testing method of the three examples provided here. Polymerase Chain Reaction is a method that allows specific DNA or RNA from a sample to be identified. It is considered to be the most rapid, reliable and accurate method of detecting biological agents at present and has revolutionised biological agent testing. The methodology uses specially devised DNA and RNA sequences to identify a target DNA or RNA sequence in a sample and selectively amplify, or duplicate, that sequence. By selecting out and duplicating only matching sequences (such as anthrax, plague or smallpox sequences) from a sample, PCR greatly increases the ability to detect even miniscule amounts of biological agent in a sample. The duplicated DNA or RNA in the final specimen can then be used for further testing and characterisation. PCR testing is able to yield results in 1-2 hours under ideal conditions with almost perfect accuracy. Coupled with PCR, subsequent genetic sequencing and phylogenetic studies can inform the evolution of a pathogen over time and geography, and characteristics which determine the virulence of the organism can be understood.
- Reflect on the differences in requirements between the testing methods discussed. Which do you think is the ideal method for detecting biological agents?
- How feasible do you think it is to develop a widespread testing that could provide early warning of a biological agent attack, or biosecurity event?