The use of microorganisms has a multi-fold hazard perspective. Some microorganisms are inherently pathogenic and very dangerous to humans e.g. anthrax by Bacillus anthracis. Others, and arguably most others, are not expected to have any negative effect on humans. However, given that some species turn pathogenic in some situations, it is a good idea to treat these other species as potentially pathogenic.
On top of this, there is a separate element of genetic modification that in itself becomes a risk.
Working with microorganisms that are known pathogens is straightforward in the sense that their pathogenicity may already be well understood, and hence the precautions required to contain the risk can be established rationally and effectively. Depending on the level of risk posed by different pathogens, different biosafety levels are implemented that guide the steps required in handling the microorganism.
Biosafety levels 1 through 4 represent the least concern species through to the species that are known to be extremely dangerous.
Protocols regarding disinfection and sterilisation would be employed to varying degrees while working with pathogenic strains. Disinfection refers to the removal of most or all microorganisms from an inanimate object, while sterilisation is a step up and involves the removal of dead cells as well as live cells, spores, viruses and any organic element that might in itself become alive under any circumstances.
A BSL-4 lab would have many extra features in place such as special protective equipment for workers to include full body cover, a negative pressure space that actively draws in air from the outside, in order to prevent airborne pathogens from escaping into the wider environment, sealed cabinets accessible only through airtight entry points for hands, and special clearance for any personnel given access to the lab.
Lower BSL microorganisms are still treated with caution under standard practice procedures. Risk assessment is an essential part of undertaking any type of work, and is done as the first step.
Risk assessments of work with microorganisms include the species, plasmids, genes as well as the procedures to be undertaken with their respective risk and hazard profiles.
Any work that comes up with an unacceptably high risk of a significant hazard, or any risk at all of a severe hazard, will simply not be attempted at all, or justification would have to be found for such work and why alternatives cannot be found.
Hazards are any potential dangers that could come out of performing the work proposed with the organisms proposed in the manner proposed. Risk is the assessment of how likely it is that each hazard will actually happen.
Hazards can be rated minor, considerable or severe. Risk can be rated low, moderate or high. This could give, for example, a minor hazard of skin irritation with a low risk, a considerable hazard of burns with a low risk and a severe hazard of poisoning with a low risk.
The minor and considerable hazards are acceptable as they are low risk. The severe hazard is also low risk, but it being severe might still deem it an unacceptable risk, however low it may be.
Mitigating risks in working with microorganisms includes wearing personal protective equipment (PPE) like lab coat, goggles and gloves, disinfection of benches and tools, sterilisation of glassware and other equipment before and after use, disposal of contaminated waste items appropriately, and labelling of items with name, contents, date and other relevant information e.g. plasmid type.
Genetically modified microorganisms (GMM) pose a type of risk on top of their being microorganisms in the first place. This is why GMM have extra protocols in place with more caution given to their handling and disposal.
Within the controlled environment of the lab, GMM behave as they are expected to. However, given the inherent uncertainty around new research practices using genetic material, it is especially worrying if these unknowns should escape the controlled lab environment.
From the get-go, research bacteria are made to not be able to survive in their wild habitat. Should they escape lab conditions, they would not be able to survive.
There are other sophisticated strategies of controlling GMM in the works. Using synthetic amino acids could enable microorganisms to carry out their metabolism in the same way, but rely on amino acids made in the lab, not found in the wild. This would render them unable to propagate in the outside environment.
Auxotrophy refers to the inability to make an essential compound for survival. This could be engineered. If this compound is used in the lab, the organism can be used and allowed to survive; however, once escaped and without this compound, it would die.
Induced lethality involves engineering a lethal response of the organism to a common compound found in the wild but not in the lab.
Gene flow prevention is less extreme, and involves only targeting the DNA of the plasmid that has been genetically modified. By adding a deadly factor to the plasmid that can be switched off in the lab, any escaped microorganism passing the plasmid on to a wild one would result in its death.
Another option might be a switch that controls DNA, so that the exposure to a certain chemical e.g. a sugar, would trigger the response to destroy the DNA, rendering the microorganism unable to live.