Tiny fish with a funny name could help with opioid crisis

A tiny fish with a funny name may help solve one of our biggest problems — the opioid crisis.  

Opioids like morphine are addictive, have side effects and aren't that effective. Newer synthetic ones, like oxycodone and fentanyl, have the same issues and don't solve chronic pain. The unpredictability of both have cost thousands of lives.

The fang blenny, a fish found in the Great Barrier Reef, has potent venom that acts the same way as opioid drugs for killing pain. It could represent a new way to look at our most effective — and problematic — pain drugs.

Why do we need new opioid drugs?

Mostly because the ones currently on the market aren't that good. We have potent opioids that are incredibly addictive and have lots of other side effects, including constipation, dizziness, nausea and altered mental condition. Or we have weak ones that simply aren't that helpful for deep and chronic pain.

As things stand, we can go into the lab and tinker with existing drugs, and hope we can decrease addictiveness while maintaining potency. But so far, that hasn't exactly been very successful.

Another approach is to look to nature. Nature has had millions of years to tinker with biologically active chemicals. We don't necessarily know where to look for these, nor have the tools to begin a search. But chemicals that have evolved to kill pain without killing you are out there somewhere — in the fang blenny fish, for example. 

What does this little fish look like?

For one, it's adorable. In fact, it's actually a common aquarium fish. There are lots of different species, some that produce venom and some that do not. They can be quite colourful, from zebra-striped to bright yellow. Each variety has a proportionately massive set of fangs, often almost half the length of its skull.

One branch of the fang blenny family tree has coupled these massive chompers with a venom that helps defend it from predators and compete with other little fish.

"We expected this venom to be intensely painful, but instead the bites are actually pain free," says associate professor Bryan Fry, head of the venom evolution laboratory at the University of Queensland's school of biological sciences. "What really surprised us was that [the fang blenny's] venom contains these opioid-acting peptides."

"Now, they're not trying to do pain killing as the intended use of the venom, rather it's been selected for the side effects. Anybody who's ever taken a pain killer knows you get a bit woozy, your blood pressure goes down, you're not terribly on your game, so in this case they're using a form of chemical doping to win this competition."

Does the fang blenny venom work on humans as a pain killer?

Likely yes, but it's only been tested on animals so far. However, the venom is not a mysterious new chemical; it's actually very similar to something we have in our bodies called enkephalin.

Because the chemical is a derivative of a type of peptide humans make naturally, says Fry, researchers are starting "much further ahead of the game" than they normally would be when exploring a potential new pain killer.

These enkephalins work like the natural pain killers in our own bodies. The question is, does the fang blenny version work better than our own? Are they more potent? Do they have fewer side effects? Most importantly, can we learn how they work and subsequently create a new drug?

So what's the next step?

There are a lot of hurdles between discovery to prescription-ready drug. The next step is to try to sequence more fang blennies. The expectation is that there could be as many as 200 different versions of these little proteins, or peptides that act like opioids, in the 12 or so venomous species of the fang blenny.

The goal now is to collect more samples, sequence the DNA and proteins, compare them to what we already know and see what kinds of variation is present in nature. Maybe nature has figured out something we would never even think of.

It certainly wouldn't be the first time. The most commonly prescribed drug for high blood pressure is captopril, a synthetic version of a snake venom. This new opioid from fang blennies has lots in common with captopril: it's protein-based which means it's relatively easily studied and mimicked and the small size means that, in pill form, it can easily cross out of the digestive tract and into the blood where it takes effect.

So the fang blenny's potential isn't just blue-sky thinking; there's a very real and somewhat straight path for studying this opioid to make it useable as a pharmaceutical.

The number one hurdle is the health of the Great Barrier Reef, where these fish live. There's an immense amount of unknown diversity in ecosystems around the world disappearing at unprecedented rates due to climate change, and the GBR is fragile among these. Current policies of both the Australian and American governments don't bode well for slowing climate change and preserving nature to its full potential to help us. 

Here's the key thing: a better opioid is worth tens of billions of dollars. The best source of inspiration for new pharmaceuticals is nature, and that's what we are destroying for a few million or even hundred million in the short term.

The reality is that the economic argument for conservation vastly outweighs the economic argument for destruction.The fang blenny populations are declining as the reef gets bleached and destroyed, and with it goes millions of years of perfecting potentially life-savings drugs for our use.