By Bersabeh Tigabu, DVM, Ph.D., Sr. Scientist/Project Manager, Merrick & Company

Films and television series like ‘Outbreak’, ‘Contagion’ and ‘The Hot Zone’ introduced the public to what it is like to work in biocontainment labs. I have been asked on several occasions whether these Hollywood movies illustrate what really is happening in these labs. I thought you might like to know some of the things I tell them based upon my experiences working as a scientist in a BSL-4 lab.

Although far from realistic, one of the good things the movie ‘Outbreak’ did is introduce the four levels of biological containment, with biosafety Level-4 (BSL-4) being the highest level (although there were numerous flaws in the filmed operations, practices, and separation between laboratories). BSL-4 labs are where scientists wear positive-pressure suits also known as “space suits”, breathe filtered air, and conduct research on the deadliest infectious agents. These include viruses for which we have no cures or vaccines, like Ebola virus and Lassa virus. Facilities that have BSL-4 labs also have several layers of security. Employees have to go through metal detectors similar to those in airports, and access to BSL-4 labs (the ‘hot’ lab) is restricted to investigators who complete rigorous training. Instead of fingerprint scanning as in ‘Outbreak’, modern BSL-4 labs use iris scanners to control access. These scanners work much like those in the movie ‘Minority Report’ where your eyes will be scanned by a camera. Unlike in ‘Minority report’ where Tom Cruise used plucked out eyes in a plastic bag to gain access to restricted areas, these scanners distinguish live irises from dead ones, preventing possible unauthorized entry or hacking of the system.

The most common question I get is, ‘what does it feel like to wear the space suit?’ First of all, working in BSL-4 lab is physically and mentally exhausting. When working in BSL-4 labs, space suits need to be hooked up to air supply hoses dangling from the ceiling, providing users with their own air supplies. As in the movies, the space suits come in “stylish” colors: blue, white, and orange. The blue suit is preferred by people working with animals as it is a little thicker and sturdier, but it is quite loud, and users must wear ear plugs. I usually wear the white suit which is lighter than the blue suit and has a much quieter air supply.

Whichever suit you wear, you have to get used to a constant flow of air over your face, and if you need to scratch or push up your glasses, it will take a while as you have to slip your hands out of the arms and up inside of the suit. If you sneeze and want to blow your nose, that is more challenging; and as you might imagine, being sealed in an airtight suit comes with some other disadvantages. Not nearly as cool as it looks in the movies, is it? Working in BSL-4 can also be lonely, unlike in Hollywood movies where scientists chat and have normal conversations while wearing space suits, in the real world, the airflow in the suit is loud and you have to shout to talk to one another. That means conversation is limited to short sentences and expressive gestures. Careful planning of bathroom breaks is also important. You need to drink enough water before going into BSL-4 to avoid dehydration, but not too much, otherwise you’ll have to go through the elaborate and time-consuming exit process to get to a bathroom. Working in BSL-4 also requires you to be detail oriented and organized. Once you are in BSL-4, if you realize that you forgot to bring something, you have to waste time in exiting the lab, which includes taking additional shower.

Working in BSL-4 is very slow. To enter, you have to change clothes and check you suit for holes or other damage before putting it on. Exiting requires you to take an eight-minute chemical shower to decontaminate the suit, then a personal shower, before you can change back into your regular clothes. When you are in the lab, you are constantly hooking and unhooking air hoses to the space suit as you move from one area to another. Working with viruses like Ebola means taking additional precautions when working in the lab, and this adds time. BSL-4 is even more challenging when you are working with animals. Animals are housed in sealed cages and strict rules have to be followed during animal handling. For our own safety, we must sedate the animals even for minor manipulations. Taking all these factors together, any work in BSL-4 takes at least three times as long as work in lower level labs, which is one reason research in BSL-4 labs lags behind studies of less-dangerous organisms.

In Hollywood movies, vaccines or antisera are prepared and are available to sick patients in a few days, or at most a month or two, and treated patients heal quickly if not miraculously. In reality, this takes much, much longer. Antisera containing antibodies that combat infectious disease can be administered after exposure and can give immediate protection during outbreaks. The problem is that the preparation of antisera is an expensive, time-consuming process.  It takes time to make these products, and sometimes it may not even be effective. Therefore, once a given preparation is determined to have an effect on a virus in cell culture, its efficacy and adverse effects must be studied in animals infected with the virus. Then it has to go through the FDA approval process. In the normal approval process, the FDA requires a clear demonstration of safety and effectiveness in humans before approval is granted. Since the efficacy of such antisera cannot be tested in humans without exposing them to deadly viruses, which is obviously unethical, the FDA has developed an alternative pathway known as the “Animal Rule” [1].

The “Animal Rule” eliminates the requirement for human efficacy studies, and instead relies upon more extensive results from efficacy studies in animals. This rule is intended to expedite the approval process so that antisera or vaccines will be available for sick patients [1,2]. The Animal Rule was applied during the 2014 Ebola outbreak in West Africa, where ZMapp (a mixture of neutralizing antibodies), which had only been tested on animals, was used to treat patients infected with Ebola virus [2,3]. Given the scientific and regulatory complexities, it is quite clear that in the real world, the Cuba Gooding, Jr. character in ‘Outbreak’ wouldn’t have been able to go into the back of a van (referred as a ‘BSL-4 mobile unit’) and produce enough antisera from a single monkey to treat thousands of infected people in the fictional town of Cedar Creek, California.

So although it seems like it’s not worth mentioning, the above examples, and countless others, distinguish Hollywood from reality- the rigor, time, complexity of high- and maximum-containment work, and the process to derive function products (e.g., vaccines) from the research is never what you see on the big screen. Maybe in celebration of National Biosafety Month, we should all grab a bag of popcorn, stream our favorite Hollywood rendition of an epidemic movie, sit back, and have a good chuckle.

References:

1. Product Development Under the Animal Rule -Guidance for Industry. October 2015. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/product-development-under-animal-rule
2. World Health Organization. 2014. Ethical considerations for use of unregistered interventions for Ebola virus disease. Also available from: https://www.who.int/csr/resources/publications/ebola/ethical-considerations/en/
3. Lyon GM, Mehta AK, Varkey JB, Brantly K, Plyler L, McElroy AK, Kraft CS, Towner JS, Spiropoulou C, Ströher U, Uyeki TM, Ribner BS, Emory Serious Communicable Diseases Unit. 2014. Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med 371:2402–2409