Will the Next Big Cancer Drug Come From the Ocean?

Pharmaceuticals are derived from a weird, wide range of natural and synthetic sources. Thanks to scientists who probe every inch of the globe, one increasingly common source for discovering natural compounds is the ocean. The anti-tumor drug trabectedin was originally made from extract from a sea squirt. Ziconotide, an analgesic for severe and chronic pain, comes from a cone snail.

Sirenas, a San Diego, California-based company, specializes in discovering marine-based therapeutics. A team from the startup goes out, an average, four times a year to bioprospect, seeking out and harvesting plant and animal species that may contain compounds helpful in treating diseases plaguing millions around the world, including malaria, tuberculosis and a variety of difficult-to-treat and incurable cancers. In the Central Pacific, California and Florida coasts, and the Caribbean, the divers are particularly interested in sea sponges and algae, such as cyanobacteria, commonly known as blue-green algae.

Sirenas co-founder and CEO Eduardo Esquenazi talked to Smithsonian.com about how a lifelong love of the ocean pulled him into marine science and why his team is committed to diving deep for potential cures for medicine’s most vexing diagnoses.

How did the idea for Sirenas come about?

I’ve always been an ocean person. I’ve had an affinity for water my whole life. I spent much of my youth in the Caribbean learning to dive and surf, enamored with ocean organisms beneath the surface. I took science courses all through high school—a lot of biology—and at Vanderbilt, I settled on neuroscience. Even though I love the ocean, my training was more lab-based in neuroscience and biology, including during graduate school in San Diego.

In grad school—this was 2002 or 2003—all was dandy and I was doing well in neuroscience. I don’t know if I was happy in a lab all the time, but I was intellectually stimulated even though I was disconnected from my desire to be outside. I’d been having pain in my abdomen. I went to student health and shortly thereafter was diagnosed with testicular cancer. Everything changed right at that moment.

On the one hand, there was a sense of relief, in that I hadn’t been feeling great physically but also, oh, maybe I don’t have to continue with grad school. I thought this could be an opportunity because I was not in a great place.

As I went through treatment—it’s a rough treatment, and mine lasted a year and a half—I began to think about the ideal life I’d like to lead.

I kept coming back to the ocean, science and making an impact in medicine because I was learning about all these cancer drugs, which were treating my condition very effectively. All of them came from nature, either plant or microbial sources. Even with a science background, I hadn’t known that, and I began to learn where medicine came from—much of it, if not from nature, then inspired by nature. So then I thought, what about the ocean? As I started researching that, I found a small but vibrant field.

As I got better, I started reaching out to people in the field, and the hotspot turned out to be Scripps Institution of Oceanography. I was already at the University of California, San Diego. After I got better, I went back to school and switched my studies to marine drug discovery with the goal of starting the company [that is now Sirenas]. It helped that my dad was an entrepreneur his whole life. That set the stage for me wanting to drive innovation. I had that gene to go after something different.

What is the process for harvesting marine-based compounds? How do you know what to search for and how it might be useful in medicine?

There’s a traditional way of doing this work—at Scripps and elsewhere. Researchers go into the field and collect certain organisms, such as sea sponges, and get certain bacteria and grow it in lab. As you progress in your career and information becomes more apparent, you can begin asking which are the organisms that tend to produce good chemistry. Then you focus on those, and it becomes about finding new types of organisms.

What we do is find a way to track every little bit of chemistry. In previous approaches, you’d go out and collect a lot of stuff and use a cancer or antibacterial test to find something useful for that specific purpose. It was like finding a needle in a haystack and then trying to figure out where the needle is useful for these diseases.

We treat that stack of hay as all needles. We look at every single molecule as being important, and we’re looking to see what all those different needles are doing. We catalog every little thing we find, test everything, and basically get a fingerprint for every needle. It’s sort of like National Security Administration spying, compiling a dossier on every person, and there are no red flags until something weird happens. And maybe it isn’t even that weird, but that’s when we start paying attention.

What’s misunderstood about what you do?

One huge thing people misunderstand is the idea that we’re doing something naturopathic, that we work in the extract supplement world. We don’t.

What we’re doing is really exploring an emerging understanding of small molecules. We collect a sea sponge, for example, but what we’re really after is everything that’s living in the sponge that makes the microbes. We have evolved out of this huge microbial diversity, and the tools and research we have today look at the chemical dance that has emerged from microbes.

How does your work ensure marine health?

Maybe in the traditional way, harvesting was harmful. Collecting tons of sponges didn’t seem bad because there was a greater good aspect to it. Researchers would find an anti-cancer compound and simply collect the sponges that make it.

That’s ancient history. Today, people harvest and cultivate in different ways. Genomic methods allow us to collect a tiny bit of an organism, and we don’t have to go back. We need a single sample, a small amount, to make elements synthetically in a lab.

MacArthur Fellow [Phil Baran], who is a co-founder, is an organic chemist, and even across our whole team, we have the ability to synthesize things we find in nature in a lab and not have to rely on going back to the ocean.

The net benefit is that we have a miniscule impact on the environment. We typically work with ocean conservancy groups and laboratories wherever we go, and we try to support educational or scientific work in those places, sharing what we know or actual financial support with local institutions. In the end, if we can show this incredible health benefit from what’s in our oceans, people will respect the environment even more, and that can drive conservation.

How do you get funding?

Largely, our funding comes from grants, including a $775,000 Gates Foundation grant, as well as partnership revenue from pharmaceutical companies built on our technology; we make our platform accessible to them. The rest has been investment from impact investors. That combination, now in higher value areas, is starting to have quite a bit of success in oncology, and we’re starting to have conversations around raising venture capital-type money for driving drug development more quickly.

When I say higher value, I mean, for example, in an area such as immuno-oncology, where we want to find more novel approaches to target certain cancers. We find things that kill cancer cells in a specific way. Then we work with companies that have antibodies that can target specific cancer cells and attract those antibodies to kill the dangerous cells. That takes a tremendous amount of work, and we need more resources to develop these sorts of assets.

What’s next for Sirenas?

We’ve filed some patent applications on payload for targeted cancer therapeutics. We believe the current combination of an emerging understanding of microbes in our world with huge explosion of computing power, informatics and artificial intelligence makes this a really exciting place to be.

In March 2017, Sirenas will be at the South by Southwest conference with Fabien Cousteau discussing the ocean and its impact on human health.

Brittany Shoot | | READ MORE

Brittany Shoot is a writer and editor based in San Francisco.