Changing the Tide of Cancer With Clams

Q&A With Dr. Michael Metzger: Changing the Tide of Cancer With Clams

When you first step into the Metzger Lab at PNRI, it might seem like any other genetics research lab—until you catch a whiff of the ocean and spot a tank full of clams. PNRI Assistant Investigator Michael Metzger, PhD’s work not only aims to help ecologists curb a contagious cancer threatening shellfish around the world but also has the potential to open the door to new cancer treatments for humans.

And don’t worry—while the clams are battling a unique contagious cancer, it’s not something humans can catch, so they’re still perfectly safe to eat.

We sat down with Dr. Metzger to learn more about what drew him to study these marine species and to hear about the exciting discoveries emerging from his lab. Here’s what he had to say.

Q: What is the focus of your lab? 

We study how cancer evolves over time and how it interacts with the organisms it affects. Most people think of a cancer as a single event in one person or organism, but we view it as an evolving entity that can teach us a lot about vulnerabilities in cancer cells.

Our work is centered on a fascinating phenomenon called bivalve transmissible neoplasia (BTN), a contagious cancer found in soft-shell clams and cockles. This cancer has evolved and adapted for centuries. By understanding how this cancer has survived and changed, and how the clams have evolved in response to it, we hope to uncover new ways to treat cancer in humans.

Unlike human cancers, which don’t spread from person to person, BTN is transmissible. Scientists have seen this phenomenon of a transmissible cancer in Tasmanian devils and dogs, but it’s especially prevalent in bivalves like clams and mussels.

BTN blurs the lines between cancer and infectious disease. It’s as if the cancer cells themselves become a sort of parasite, jumping from one animal to another. This challenges our traditional definitions and forces us to rethink how we categorize and study such diseases.

Studying BTN offers unique insights into cancer biology. For one, it shows us that cancer can be much more adaptable than we typically think. By understanding how BTN has persisted and spread over centuries, we can identify potential targets for new treatments.

Additionally, our work underscores the importance of looking at cancer as part of a broader ecological system. Cancer doesn’t exist in a vacuum—it’s influenced by and influences the environment around it. This holistic view could lead to more effective and sustainable approaches to cancer treatment.

Soon, we hope to look across all the mutations and see if there is anything about BTN that has not changed—some feature that remains constant. If we find that there are features that are conserved, it could mean that they are required for this cancer and other cancers to grow and spread. And that could open the door to new ways to treat cancer. 

Q: What sparked your interest in this work?

My journey into this field was somewhat accidental. I’ve always been fascinated by evolution and how hosts and pathogens evolve together. During my postdoc in Stephen Goff’s lab at Columbia University, a marine biologist approached us and asked if we could identify a retrovirus that was infecting clams. We initially started looking for a virus, but soon discovered it was actually a cancer spreading from clam to clam.

This contagious cancer likely originated from a single clam around 400 years ago. Its cells were released into the water, where they were able to enter into other clams, creating a sort of metastasis on a larger scale—spreading not within one organism, but across many.

Since then, I’ve been fascinated by this phenomenon. We’re currently studying how the disease spreads among basket cockles and soft-shell clams on the West Coast, where this kind of cancer has not previously been found.

Q: What recent discoveries from your lab are you most excited about?

One of our most exciting findings is the detailed genomic analysis of BTN, led by Sam Hart, a brilliant graduate student in my lab who just finished his PhD. Sam built what we call a molecular clock, allowing us to estimate the age of these cancers by analyzing mutations in samples taken over a 10-year span. He found that the cancer in soft-shell clams is about 400 years old. This means the original clam that developed the first cancer lived around four centuries ago, and since then, these cancer cells have been spreading through clam populations by jumping from animal to animal.

His research revealed a lot of unexpected findings. We found that the cancer genomes were far more unstable than we initially thought. They’ve undergone genetic changes so drastic that it’s surprising the cancer still survives after several hundred years. So now we’re asking: What hasn’t changed? And could that reveal some quintessential part of a cancer’s DNA we could target as a new cancer treatment.

Despite this cancer’s perplexing ability to survive and spread, some clams have evolved mechanisms to resist it, and understanding those mechanisms could have big implications for ecology and human health.

What’s really intriguing is that we’ve found multiple independent origins of these cancers in other bivalve species. We’ve identified nearly a dozen different lineages, but we don’t yet know if they emerged last week or centuries ago. That’s something we’re still trying to figure out.

Q: How does working at an independent research institute benefit your work? 

PNRI is a unique environment that encourages interdisciplinary collaboration. My work spans genome science, marine biology, cancer biology, and ecology—fields that don’t typically overlap. In a more traditional setting, it might be difficult to pursue such diverse research, but at PNRI, I have the freedom to follow the science wherever it leads.

Our work doesn’t fit neatly into one scientific category. BTN is a cancer, but it’s also a transmissible disease and, in some ways, a parasitic organism. This creates challenges, as traditional fields like marine biology or cancer research may not fully embrace our interdisciplinary approach.

Yet, this challenge is also an opportunity to innovate. By blending tools and methods from various disciplines, we’ve made some of our most exciting discoveries. PNRI encourages us to think creatively about how these cancers have evolved and mutated, as well as developing new tools and methods to find answers.

For instance, when my lab was studying transposons—genes within cancer cells that jump around the genome—the technology available to us wasn’t suited to the type of analysis we wanted to conduct. So, we created a new computer program to analyze our data and pinpoint where and when those genes moved.

Q: What’s creative about your lab’s research?

Well, there aren’t too many scientists studying cancer in clams! Our work is outside the box to begin with. And it has both ecological and human health implications. 

For example, we’re collaborating with the Suquamish Tribe and the Puget Sound Restoration Fund (PSRF) to study BTN in local basket cockles. The tribe noticed a decline in cockle populations and, through health screenings, discovered that some of the animals had cancer. These cockles are culturally significant and an important food source for the tribe, and we are continuing to work with tribal shellfish biologists on this disease.

We formed a partnership with the Suquamish Tribe, PSRF, Washington Department of Fish and Wildlife, and several other groups on the East Coast and West Coast to identify the cancer, where it is, and how it’s spreading. This is important for understanding the cancer itself and it will inform how the tribe and other groups restore the shellfish population. They ultimately want to create a hatchery and do it in a way where the cancer won’t spread and the shellfish will survive. We’re working with them to determine the best way to do that. 

Q: How will people in the future benefit from this research?

Our work in ecology and in human health are closely intertwined: You can’t understand the evolution of resistance to cancer and the implications for human health unless you understand how cancer spreads in the wild and affects the animals. And understanding how cancer affects the animals can have big implications for the environment, ecology, and the communities that rely on these shellfish for food. 

Our partnership the Suquamish Tribe and the Puget Sound Restoration Fund is incredibly rewarding because it connects our research directly to real-world applications. It’s not just about understanding BTN in a lab—it’s about making a tangible difference in the ecosystem and the lives of the people who depend on these animals.

On the human health side, we’re looking at how some clams have evolved to resist BTN. If we can figure out how these clams block the cancer, we might be able to apply that knowledge to develop new cancer treatments for humans.

Q: What do you like to do in your spare time?

I spend most of my spare time with my family. We love outdoor activities like camping and backpacking. We’ve taken our 7-year-old on some pretty adventurous trips, and now that our younger one is ten months old, we’ve been excited to bring him out for his first camping trips this summer. No backpacking yet, but maybe in the future. We’ll see how much we can carry!

Q: Do you actually like clams?

I do! I’ve eaten a lot more shellfish since starting this research. Growing up in Arizona, I didn’t have much exposure to clams, but now I really appreciate them. They’re fascinating creatures, and the more I study them, the more I enjoy learning about them—and eating them, too.

Dive Deeper

Dive deeper into Dr. Metzger’s work by listening to his podcast episode “Future of Healthcare from a Clam” (link coming soon!) Learn more about the Metzger Lab and connect with PNRI to meet Michael and experience his groundbreaking science in person.