Viruses Are the Dark Matter of Biology - and a Future Billion Dollar Industry

Sam Westreich, PhD

Future Nobel prizes — and life-saving drugs — are certainly hidden in this undiscovered world.

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Like a cat under a blanket, viruses are amazing and hidden in plain sight.Photo by Francesco Ungaro on Unsplash

“I just want to say one word to you, one word,” Mr. McGuire says in the classic movie The Graduate. “Plastics. There’s a great future in plastics.”

That movie came out in 1967, and the advice seems accurate; we have plastics everywhere (most likely far too many plastics, considering how microplastics are a huge problem). But what’s the best one-word recommendation to give to aspiring new graduates today?

If I had to give a single word to prospective scientists and researchers: viruses.

Viruses are deceptively simple. Tiny genomes, barely considered alive (and not even alive, depending on your definition of life). But they are everywhere, at levels that you likely can’t even imagine.

And they play vital roles in the most basic aspects of your life — and in high level conversations about worldwide issues like climate change.

And even though we’ve known about their existence since the late 1800s, we’ve barely even begun to discover them.

More viruses in a cup of water than humans in the world

As a microbiome scientist, I probably have a better idea than most people about how bacteria are just about everywhere, covering everything from our skin to our home surfaces to the dirt outside our homes. (For example, you’ve got an insane level of microbe diversity in your belly button; it’s the microscopic equivalent of a tropical rainforest.)

But in terms of sheer numbers, bacteria are nothing compared to viruses.

There are an estimated 5 million trillion trillion bacteria on Earth — that’s a 5 with 30 zeroes following it.

But viruses? One Nature article suggests that there are 5 x 10³¹ viruses on Earth — ten viruses for every single bacterium.

At a certain point, these numbers just lose all meaning. Is it better to say that there are more than a billion viruses on Earth for every single known star in the entire universe? Or that there are so many viruses, they kill between 20–40% of all bacteria on Earth every single day? Or that if you laid out every single microscopic virus in a long chain, end to end, it would stretch for 100 million light years — long enough to stretch from Earth to the center of the Milky Way galaxy and back, almost 2,000 times?

Let’s just call it a lot. Viruses outnumber pretty much every other creature in existence, even if you added every other creature together.

And, perhaps because they’re so small, or maybe because they’re so hard to consistently classify, they are drastically under-studied compared to most other living creatures.

Harnessing the power of viruses for our own benefit

It’s a sad but widely accepted truth that, if you want to get serious funding to study something, you have to be able to show that it offers a tangible benefit.

Viruses could pay off in that regard. Let’s take a look at two big ways that viruses might lead to new breakthroughs in medicine: as bacteriophages, and as genetic vectors.

Bacteriophages

A bacteriophage is a virus that attacks bacteria. When we see a picture of a virus with its polyhedral head, slender tube body and six spiky legs, looking like some sort of freaky science fiction insect, we’re looking at a bacteriophage.

As their name suggests, these viruses kill bacteria. They do so by injecting their DNA into the bacterial cell, taking over the bacterium’s machinery and hijacking it to make many more copies of the virus. Eventually, the bacterial cell bursts open, releasing the newly copied viruses out to seek more targets.

Bacteriophages offer a few advantages over traditional antibiotics:

  1. They are very specific, with most bacteriophages only targeting a single species of bacterium. This makes them more specific than antibiotics, which kill all bacteria — bad pathogens, but also good probiotic species that we would prefer to leave alive.
  2. They aren’t as likely to induce mutations that lead to “superbugs.” Since bacterial antibiotic resistance comes from modifying specific receptors or proteins, it won’t help them resist viral takeover.
  3. Bacteriophages will keep multiplying as long as their target bacterium is present, so only one dose is needed.
  4. Overall, bacteriophages are pretty gentle on their surroundings. They’ll kill their specific target bacterium, but they won’t usually alter their environment or cause widespread damage.

Bacteriophage therapy does have disadvantages, as well. Some bacteria could potentially develop phage resistance. This also requires that doctors know exactly what type of bacteria is infecting someone, and requires “live” phage samples to be on hand to administer. Phages could also potentially activate the immune system, which we want to minimize in treatments.

Phages aren’t yet approved for treating people, in either the U.S. or in Europe, but they are used on processed foods to help kill off some food-borne illnesses, like salmonella and listeria.

An area with big promise to offer the new form of “precision antibiotics” but with more research needed?

That sounds like a big green light to prospective scientists.

Genetic vectors

Gene therapy is the cool science-fiction idea of the future. Alter your genetics by inserting custom machinery to make precision changes to your genome? Hit me up with some plasmids!

But there’s a big problem here — unlike in a lab environment, all our cells are not easily reachable. How do you get your tweaked gene + machinery into all the target cells inside a living, breathing human or animal?

We can’t just inject the raw DNA into the bloodstream; it gets degraded and destroyed before it reaches the target cells.

What we need is a wrapper of some sort, a protective sheath to encase the DNA that can also selectively bind to the target cells, so we only put the DNA into the cells where we want it to go…

…like a virus capsule.

Viral vectors for gene therapy have been an idea for a while now, mainly using adeno-associated viruses (AAVs). These viruses normally don’t cause much of a reaction in people, with a very mild immune response. That makes them good candidates to carry the gene therapy machinery we want, without the risk of triggering a dangerous inflammation flare-up in the patient.

Of course, there are still challenges to overcome. Namely:

  1. The immune system. If someone’s immune system recognizes the gene vector, it can create antibodies that both cause an inflammatory response, and also destroy the vector before it can reach its target. This can also mean that gene therapy will be less effective each time it’s used.
  2. Need for large doses. If you want to be sure of reaching enough cells, you’ll need to put in a lot of virus, which is expensive to manufacture and increases the risk that the immune system will overreact.
  3. Getting the specific response inside the target cell. This is a fine line between “not enough response” and “too much response”, while also wanting to avoid “off-target effects” (think: screwing up another gene that needs to keep acting normally!). This is less on the viral vector and more on its contents, but still a challenge in gene therapy.

Gene therapy is still largely a “someday” technology, but viruses currently offer one of the best routes for delivery.

After all, if there is a solution that has survived and evolved for millions of years in nature, why not start there?

In summary: most viruses are little understood but have big promise

Viruses are a mystery to us, by and large. One study suggests that, just in mammals, there are at least 320,000 undiscovered viruses. And there are far, far more in nature that target bacteria or other microscopic species that have yet to be uncovered.

Viruses have lots of promise in medicine, for treating everything from bacterial infections, to helping with food safety, to aiding in gene therapy. We’re going to need to find or design very specific, customized viruses for our needs, but they offer a nearly infinitely flexible platform.

We often think of the unknown as being far away, out in space or in the deepest trenches of the ocean. But there’s plenty of unknown, never before identified creatures right in front of us, or even literally inside of us.

Perhaps the next virus to make headlines won’t be a disease, but will be a miraculous treatment?

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A microbiome scientist working at a tech startup in Silicon Valley, Sam Westreich provides insights into science and technology, exploring the strangest areas of biology, science, and biotechnology.

Mountain View, CA
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