Putting the "e" in DNA

The Wall Street Journal had a great article a couple days ago that tickled my fancy on two fronts: DNA, and the deep ocean.  Both fascinate me. It introduced me to a term I’d not heard before but have now discovered is a thing: “eDNA.”  It’s something I suspect we’ll be hearing more about, and a technique we’ll be using much more, in the years to come.

Credit: USGS

The article, Finding New Drugs From the Deep Sea via ‘eDNA’, talks about a different approach to discovering potential sources of new medicines: “environmental DNA,” or eDNA.  As the US Geological Survey describes it: “Environmental DNA (eDNA) is nuclear or mitochondrial DNA that is released from an organism into the environment.” You may not want to know this, but “Sources of eDNA include secreted feces, mucous, and gametes; shed skin and hair; and carcasses.”

 

As Elizabeth Ann Brown wrote in Science this summer:

In the last decade or so, environmental DNA, or eDNA, has revolutionised marine and aquatic research by allowing scientists to sample “an entire ecosystem” with a litre of water… It’s a relatively cheap, noninvasive, and simple technique that can be modified to study any form of life, and it often requires less time and labour to employ than previous methods.

For decades scientists have searched for interesting new organisms/molecules that might be useful in developing drugs for humans.  Nature is, after all, a master chemist, and evolution has featured a continual battle between organisms – developing toxins to kill or disable other organisms, developing defenses against those, and so on ad infinitum.  Researchers go to rainforests, they dig in soil, they search in trash; anywhere you can find life (and that’s pretty much everywhere) there are likely to be organisms, some of which may have developed interesting molecules. 

Credit: FISHBIO

 

The thing is, we’re just scratching the surface.  Literally.  The ocean is estimated to account for 99.5% of all living space on earth.  One doesn’t have to go too far underwater for it to get dark and have pressures that would crush a human.  It has been said before, but we know more about the far side of the moon than our ocean floors. We wonder about discovering alien life on other worlds but don’t have any concept of how alien lifeforms in the ocean are.

 

We’ve developed submersibles that can reach the ocean floors, but they’re expensive to operate, have severe limitations about how long they can stay submerged, and have difficult time capturing and bringing back viable specimens.  The WSJ article talks about a more flexible approach: “ocean-going robots with onboard DNA-sequencing gear.” Kobun Truelove, senior research technician at the Monterey Bay Aquarium Research Institute, told WSJ:

The ultimate goal is an underwater vehicle that collects environmental DNA samples, sequences them and then sends the data back to the lab.  We would like to set up a network where you would have these autonomous vehicles out there sampling and then basically be getting the data back in real time.

More than 1,000 compounds derived from marine organisms have shown potentially useful medical properties, according to the article, with 15 drugs so developed already approved and another 29 in clinical trials. “We’re not starting with the chemical,” Bradley Moore, professor of marine chemical biology at Scripps Institution of Oceanography, told WSJ. “We are starting with the DNA that tells me all the genes that encode for the production of one of these chemicals.”

 

Of course, there’s a lot to be done between now and the new world. The fully functioning submersible “lab in a can” is still a few years off.  More problematic is that compounds are often produced in response to threats or other environmental conditions; “We need to study these interactions in situ because it’s almost impossible to replicate them in the lab,” said Katherine Duncan, senior lecturer in marine microbial ecology at the University of Strathclyde.

 

In the meantime, eDNA is being used in a number of other contexts. Looking to see if invasive carp are present but don’t want to wait until someone catches one?  Use eDNA. Want to document biodiversity on Mt. Everest?  Use eDNA. Want to do a microbial census for an entire ecosystem?  Use eDNA. Want to know how many species have DNA on the tea or spices you buy in the grocery store?  Use eDNA (hint: it is a lot more than you suspect). Even trying to identify some of the estimated 41,000 missing crew members from WWII underwater crashes?  Use eDNA.

 

There’s a lot of hype these days about how AI is going to revolutionize drug discovery, but for the foreseeable future AI may be helpful but not critical.  Adityo Prakash, CEO of Verseon, told Datanami that, compared to all the compounds in nature, all the compounds that drug companies might be testing are trivial: “You realize, you’re not even fishing in a tidepool.  You’re fishing in a tiny little shot glass.” 

 

We’re going to need to go fishing in the ocean to find those future medicines, and we’ll need to use eDNA.

The use for eDNA that I started wondering about is in helping decipher our microbiome.  We’ve been aware of it for a couple decades now, had projects like the Human Microbiome Project, and have come to conclude that its cells outnumber our own, But we don’t know what many/most of them are, we don’t know the effects that most of them (or their absence) have on us, and can’t culture most of them outside our bodies.  Whatever knowledge of our microbiome we have gained primarily has been from people in developed nations; “It is clear that our understanding of the ‘human’ microbiome does not include most humans,” one scientist admits.

It seems like something eDNA could help shed light on.

Last year I wrote about the potential wastewater monitoring has for tracking our health, at both a population and a personal level.  We should be taking advantage of that, and we should be figuring out how to use eDNA at scale to help us better understand the world around us.  And maybe to find the next generations of miracle drugs.