Here's How Mass Effect's Biological Warfare Is Scientifically Possible

Mass Effect’s genophage is one of the few fictions in gaming that is easiest to match to real science. We can already engineer viruses that manipulate genetics within biological systems. While such a bioweaponized feat is difficult to create within model animals (let alone sapient life) let's have some fun speculating how close theory can be to practice.

In Mass Effect, the genophage was a Salarian-engineered virus capable of sterilizing the entire Krogan population. This reoccurring plot device was used to create friction between alien Krogans, Salarians and Turians as well as develop several of Mass Effect’s characters (particularly, Mordin Solus). It brought up the necessary moral dilemmas to challenge players outside of running and gunning. It reminded us that we can be accountable for our actions.

So, how easy is it to grow a virus? Well we've got to pick from some of the most virulent strains out there as blueprints... Lab practices have effectively eliminated the pathogenicity of HIV, herpes, and hepatitis allowing them to manipulated as empty vehicles to carry genetic information of our choosing.

In essence, a virus can be considered the sum of a protein “envelope,” capsid “core” and a viral genome. Their genome is often sufficient enough to carry the information to make the rest of the virus (capsid and envelope) and is the easiest to manipulate. When we decide to make a virus we often build each of these components separately with host cells and use assembly proteins to combine them to into functional viruses.

Lentiviruses are current gold standards in engineered viruses. Three plasmids code all the components of a virus, which uses “producer cells” as hosts.

So now that you have a viral vehicle to carry information, how would this virus carry out reproductive genocide?

By its own definition the genophage was a virus designed to "eat up" endogenous Krogan DNA and introduce mutations that cause sterility. Surprisingly we've relied on several proteins and enzymes that "eat up" DNA to carry out any type of genetic manipulation.

There are proteins in nature that are known to cut DNA (i.e.: Restriction enzymes or DNAses), unfortunately in these cases they cut short sequences (restriction enzymes) or non-specific (DNAses). It's important to have a long "target sequence" since a short sequence can show up a number of times across any genome (think about how often the word "the" shows up in a book vs "theological"). In this case, you need tools that can target long pieces of DNA like manmade zinc-finger nucleases (ZFN for short). ZFNs can both bind a sequence of DNA (7-8 letters long) and cut whatever that is bound. It is possible to have several ZFN attached to each other in series to specifically recognise longer sequences of DNA (i.e.: one ZFN for each th,eo, lo, gi, and cal). In practice, the information to build these ZFNs can be packaged into a viral genome and used to target unique pieces of DNA.

Think Christmas lights alternating colours to make a recognisable pattern... This pattern aligns with a DNA sequence effectively slicing and dicing DNA sequences of your choice.

(Left) Zinc Finger protein wrapped around DNA (Right) Restriction enzyme EcoRI cutting DNA.

So now that you've got your virus and the right tool to "eat" Krogan DNA, how do you pick out a gene that can cause sterility? Assuming Salarians sequenced more than one species on Krogan homeworld, Tuchanka, the wizardry of bioinformatics could give you a decent understanding of their evolutionary origins. It's important to understand where you're coming from since the conservation of specific genes often indicates how important they are (hmmm, for let's say, reproduction).

For example, pathways that dictate cell cycle and limb growth are largely conserved from humans to fruit flies. In humans you would consider folate metabolism since known mutations in these pathways result in stillbirths (i.e.: MTHFR mutations result in stillbirth in 1:1000 pregnancies). Other viable gene targets could affect sperm motility, uterine conditions, etc.

Needless to say a great deal of fine tuning would get you exactly where you would need to go to make a working genophage. The science is out there but thankfully we use it to dissect a gene’s function for basic research and sometimes make night lights out of mice.

Green fluorescent protein is commonly used as a reporter when playing with these viruses to validate the efficacy of your infection.

In practice, you would have to overcome Krogan immunity and mediate the lethality of the virus itself. In fact it's been so difficult to engineer these viruses that currently only one has made it past trials, the oncolytic virus (designed to fight cancer).

Ethically, the genophage served as an ugly reminder of human history in the early 20th century where several countries practiced forced sterilization, often as part of a eugenics program. While this piece by no means condones the creation of race-obliterating viruses or forced sterilization, it is worth noting that there are technologies that allow even the wildest fictions a little more plausibility. But hopefully not...

Sebastian Alvarado is a postdoctoral fellow at Stanford and founder of Thwacke! For more science and video games follow him us Twitter and Facebook!

Protein structures courtesy of the Protein Data Bank


    Oh man I'm trying resist saying this but I've been playing a lot of Mass Effect lately so I can't help but get my nerd on.

    The genophage did not cause sterilty rather it controlled the birthrate of Krogans to sustainable levels. Mordin emphasizes this point a lot and that it would have been easier to just make a sterlity plague rather than a birth control plague.

    Living on a planet with an extremelly hostile environment the Krogans evolved a very high birth rate to counter their very high death rate. When the Krogan expanded beyond their planet to more hospitable worlds their population exploded. The same can be seen on earth, particularly in Australia when a species is introduced into a new environment that has no natural predators and ends up becoming a pest that destroys the environment.

      Very much in agreement. The author should at least play the game instead of speed reading through the wiki page to avoid such a gaffe.

      That said, you yourself have made a few assumptions which may not be correct. Tuchunka only became a radioactive wasteland after they were uplifted. Before, they were stable enough to build their 'lost cities'. Quite a civilized time.

      Last edited 16/05/13 2:04 pm

        Tuchanka became a nuclear wasteland when they first split the atom - before the Salarian uplift. That's why the Shroud was built to induce good will and to prevent Tuchanka from getting any worse.

        Also; the genophage worked by sterilising all but a few Krogan females, that's why a few females are fertile, but most only produce still born children. I would call that a sterility plague.

        Yes but before it was a radioactive wasteland it was just as inhospitable where even the plants were as deadly as the animals.

      a species is introduced into a new environment that has no natural predators and ends up becoming a pest that destroys the environment.

      Holy shit, human beings are pests that destroy the environment.

      Last edited 16/05/13 6:00 pm

        *face palm* why would you think of yourself as a pest, This irritates me

          Because it's true.

            We are not pests, Rabbits are pests we are an intelligent race but we are young and dumb. we need time to grow. I love humanity It's the most beautiful species i know of and our potential is limited by our minds.

              If we damage the biosphere to the point where we become extinct, then yes it will have been proved that we were pests. Sadly there will be no humans left to understand the significance by that point.

    All the bellyaching about the genophage in Mass Effect was quite foolish though since it was in the context of species destroying galactic war. That was one of the weakest parts of the series thematically- as if it was somehow awful and horrible to reduce their birth count but it's perfectly ok to wipe out entire planets full of your enemies and wipe out entire species.
    Silly American right-to-lifers.

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