• Alex Cloherty

1, 2, 3, 4, Your Biosafety Level Score

Updated: Jul 29, 2020

As a scientist working with potentially dangerous microbes, a lot of what I do is actually planning, containment, and running around between different labs with different biosafety levels. I often start an experiment at our biosafety level 1 lab, then head to the biosafety level 3 lab to do a viral infection, and then finish the experiment by fixing (i.e. preserving - and in a way that inactivates the virus) cells so that it can safely be brought back to a biosafety level 1 lab.

Today's post is in response to a question from my Dad. SInce I (and many other science communicators) have been mentioning different biosafety levels in my last posts, he asked, "Can you give a primer on the different biosafety levels for biology labs?"

When working with living organisms, it isn't always easy to decide on a strict categorization for how they should be worked with. This is because there is a wide potential spectrum of risk for working with different viruses and bacteria, which also changes depending on nuances in your planned experiments. For instance, if I am working only with the genetic material of HIV-1, there is less risk for accidental contamination of myself versus when I am working with human cells that I'm infecting with HIV-1. That is because when both "permissive" cells (i.e. cells that can be infected by the virus in question) and the virus are present, there is potential for the virus to replicate and make a lot more of itself. In the absence of permissive cells ready to be infected, on the other hand, it is much less likely that there will be any accidental replication of HIV-1. The genetic material of a virus alone won't typically be able to make more of itself without a host cell.

To take into account such intricacies, scientific institutions and governments have together built extremely detailed guidelines that determine in what kind of lab different experiments can be carried out in. Whenever I want to use a completely new virus, or a completely new cell type, in my experiments, before I start I need to first comb through a giant spreadsheet managed by my institution. This spreadsheet which details what is already allowed under our existing biosafety permits, and in what labs these microbes, or combinations of microbes and cells, can be used. For example, say I want to start using a new cell line (a type of immortalized cell that researchers use because they're easy to work with) for my HIV-1 infection experiments. If that combination isn't already on the giant spreadsheet, I will need to submit a new permit before I can go ahead with my planned experiments.

But, let's not get too much into those nitpicky details here. To start, the main thing you need to know about microbiology lab biosafety levels is that there are four different levels, and those levels are based on both biosafety and biosecurity.

Biosafety considerations are in regards to situations like the example I gave above, in which we want to avoid accidental contamination of workers and the environment. Biosecurity, on the other hand, encompasses the more nefarious side of things. Biosecurity is all about considering the potential for intentional release of harmful pathogens - for example theft of samples, or bioterrorism. Biosafety can be defined as "the protection of microbiological assets from theft, loss or diversion, which could lead to the inappropriate use of these agents to cause public health harm".

The four different steps of biosafety levels take into account both of these issues, and at each laboratory level there are different requirements for, for example, personal protective equipment, sample treatment, and waste disposal.

Biosafety Level (BSL) 1 labs are the least 'strict', and are only used for work with known microbes that are unlikely to cause harm to people or the environment. Our BSL1 lab is where I work with donated blood or skin from healthy patients. If you think about it, this makes sense, since these are materials that get into the environment anyways. Us humans are pretty messy - we're bleeding or shedding skin all the time.

The next step up, Biosafety Level 2, is where the more strict containment measures start. BSL2 labs are where you need to go if you want to work with pathogens that can cause human diseases, or entail some risk to the environment, like hepatitis C or influenza.Oftentimes, genetically modifying a microbe will also bring it up to biosafety level 2. For example, over the last weeks I have been 'feeding' bacteria DNA that encodes pieces of genetically modified SARS-CoV-2, in order to make stocks of the novel coronavirus to use in our experiments. This was all done at our BSL2 lab.

Next comes Biosafety Level 3, where we deal with the big guns. At BSL3 labs, you will find pathogens that cause serious, and potentially life-threatening, diseases, like tuberculosis and SARS-CoV-2. Another consideration for bringing pathogens up to BSL3, is how easily they transmit. The stricter containment procedures of a BSL3 lab are necessary when pathogens can hang around in the air to later infect a new host, like SARS-CoV-2 does. This ability to survive while floating around sneakily in the air indeed makes it trickier, but not impossible, to contain microbes. One way we keep them in is by having negative air pressure in BSL3 labs. This means that when you enter the lab through the doors, there is a one-way flow of air into, but not out of, the lab. Air only ever leaves the lab through a filtration system. The result of this is two-fold: infectious particles are safely filtered out and prevented from escaping the lab, and the doors are much harder to open going out compared to going in. When I'm a bit sleepy at the end of the workday, I regularly need a second try to open the door of the BSL3 lab when I am on my way out. Although HIV-1 is now technically BSL2, because there is excellent treatment available and it is relatively difficult to accidentally infect yourself with it in the lab, at my workplace we always work with this nasty virus at our BSL3 lab. It's always ok to go up in biosafety level and be more careful, but never to go back down and take unnecessary risks.

Finally, Biosafety Level 4 is where the scariest little monsters are found. BSL4 covers pathogens like Ebolavirus, which transmit exceptionally easily, cause severe and life-threatening disease, and do not have any cure, specific treatment, and/or vaccine. Microbes may also be bumped up to BSL4 when they have a high potential risk for bioterrorism - smallpox and Bacillus anthracis, the causative agent of anthrax, for example. For this biosafety level, I don't have any personal examples - I have not yet leveled up to face these bosses.

That's all for this week - see you next time.


P.S. Shoutout to Feist for the title inspiration. This song is still a classic in my brain.

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