Transmissible Cancer in Bivalves: What We Know About BTN (Devilish Diseases Part 4)
A transmissible cancer in bivalves poses a unique challenge to marine life and the ecosystems they sustain.
Earth’s oceans are full of life forms and ecosystems that we’re really only beginning to understand. Some of the most unassuming of these organisms are the bivalves. Clams, mussels, cockles, and other shellfish that play particularly important roles in maintaining the ecological balance in these ecosystems. But these quiet custodial creatures are facing a strange and sinister threat, a cancer that moves between organisms and across vast areas of seawater to new victims. We’ve covered a couple of these transmissible cancers on here before in the Devilish Diseases series with Canine Transmissible Venereal Tumors (theedgeofepidemiology.substack.com/p/the-ancient-cancer-that-crossed-continents) and Tasmanian Devil Facial Tumor Disease (theedgeofepidemiology.substack.com/p/the-devils-burden). These are cancers where the vector of transmission is the actual cancer cell itself, not some cancer-causing agent (think HPV and cervical cancer).
The cancer spreading among bivalve species is known as Bivalve Transmissible Neoplasia (BTN) and is like leukemias in how it behaves. First identified in soft-shelled clams (Mya erenaria), BTN has since been found in multiple species across oceans and continents. Its ability to cross ecological boundaries makes BTN a daunting problem for researchers to tackle. Here we will trace the origins of the disease, look at its molecular mechanisms, and see the impact on ocean ecosystems to better understand this devilish disease.
Discovery of BTN
The discovery of BTN started as a bit of a mystery. Soft-shell clam populations along the east coast of North America were experiencing massive die-offs from the 1970s into the 2000s. Initially attributed to environmental stressors like pollution, climate change, or some mystery pathogen, the patterns just didn’t align. Researchers were finding healthy looking clams dying en masse with no obvious signs of disease 1. A closer examination of the clams showed the presence of abnormal cells circulating in the clams’ equivalent of blood called the hemolymph. The cells were strikingly similar to leukemia, but what stood out was how uniform the cells were. Unlike typical cancers, where mutations vary from host to host, these cancer cells were genetically identical across individuals 2. This was the first sign that BTN wasn’t just another cancer, but something entirely different.
BTN was confirmed as a transmissible cancer via genetic analyses. Researchers found that the cancer cells were not derived from their current host but shared a common origin in one clam that was a live hundreds of years ago 3. This discovery put BTN alongside the few known transmissible cancers in nature including CTVT and DFTD. The realization that BTN was able to cross species added another layer of complexity to the disease. While initially ID’d in soft-shell clams, BTN has since been found in multiple bivalve species including mussels (Mytilus trossulus and Mutilus edulis), cockles (Cerastoderma edule), and the golden carpet shell clam (Polititapes aures) 2,4. This cross-species transmission is a sign of BTN having a remarkable adaptability profile and poses some significant challenges for the researchers studying its spread.
BTN’s ability to travel vast distances also complicates the identification and monitoring efforts. It has been suggested that international shipping has accidentally been helping the disease spread, and is now found on both sides of the Atlantic in North and South America, and Europe 5. BTN cells can survive independently in seawater for extended periods of time, making it possible for the cells to travel between distant populations on the ocean currents 6. These early findings were the foundation to uncovering BTN’s evolutionary dynamics, which tell an extraordinary story of a cancer that has persisted and evolved over centuries.
Evolutionary Dynamics
Like all cancers, BTN began as a single celll breaking the usual rules of growth and reproduction, but it is unique in that the journey didn’t end with the original host. BTN took on a life of its own, becoming an immortal clonal lineage.
The Origins of BTN
Like I said earlier, BTN started with a single soft-shelled clam, patient zero in our story. Since then, it has persisted for centuries, with estimates suggesting sublineages in that species diverged somewhere around 315 years ago, possibly longer, but a few hundred years is a safe estimate. These sublineages, found along the east coast of the USA and another found in Prince Edward Island (PEI), Canada, give us some ideas as to the evolutionary timeline of BTN. Despite these divergence dates, BTN likely predates these and could have a much deeper history 1.
BTN’s ability to persist is tied to its genomic instability. The cancer shows high mutation rates, structural rearrangements, and copy number alterations that drive its ability to adapt to new hosts and environments. Interestingly, the mutation rates differ across sub-lineages, with PEI samples showing fewer mutations than those from the United States. While the reasons for these differences are unclear, they reflect BTN’s capacity to evolve in response to diverse ecological pressures 4.
Evolutionary Arms Race
The relationship between BTN and its hosts is shaped by a constant tug-of-war. Hosts develop resistance mechanisms to combat BTN, while the cancer evolves to evade these defenses. This interplay exemplifies the Red Queen hypothesis, which describes the continuous evolutionary arms race between hosts and pathogens 7.
In some species, signs of resistance have emerged. For example, certain Pacific blue mussel populations appear to have evolved mechanisms to block BTN infection, while soft-shell clams have shown the ability to suppress BTN after both natural and experimental exposure. These examples suggest that host populations are actively adapting in response to the disease, shaping BTN’s evolutionary trajectory 1,8.
Molecular Mechanisms
The transmission of BTN is as remarkable as its origins. Unlike traditional cancers, BTN doesn’t rely on a mutagen or pathogen to induce cancerous growth in its host. Instead, the cancer cells themselves are the vector, moving directly between hosts. The filter feeding animals take in the free-floating cells from the seawater around them. This unique mode of transmission raises intriguing questions about how BTN cells survive, spread, and evade host defenses.
Cellular Adaptations
BTN cells possess several adaptations that enable them to invade and thrive in new hosts. One key adaptation is their ability to evade host immune systems. In healthy bivalves, immune cells would typically recognize and destroy foreign cells. BTN cells, however, seem to exploit weaknesses in the bivalve immune response, possibly by mimicking host cells or suppressing immune activation.
The cancer’s ability to infect multiple species further underscores its adaptability. BTN likely targets conserved biological pathways shared among bivalves, allowing it to thrive in its diverse bivalve hosts. This cross-species transmissibility highlights BTN’s evolutionary success and presents significant challenges for researchers attempting to understand and mitigate its spread 4.
Comparison to Other Transmissible Cancers
BTN shares some traits with other transmissible cancers, such as Canine Transmissible Venereal Tumor (CTVT) and Tasmanian Devil Facial Tumor Disease (DFTD). Like BTN, these cancers rely on direct transmission of cancer cells rather than an external agent. All three cancers show remarkable genomic instability, which contributes to their adaptability and long-term survival.
However, BTN’s mode of spread is uniquely aquatic. Unlike CTVT or DFTD, which rely on physical contact for transmission, BTN cells can travel through the water, making its spread less dependent on host behavior. This environmental vector adds a layer of complexity to BTN’s biology, further distinguishing it from its terrestrial counterparts.
Implications for Host Health
Once inside a new host, BTN cells behave much like leukemic cells in humans, disrupting normal physiological processes. The infected bivalve’s hemolymph becomes crowded with BTN cells, impairing its ability to transport nutrients, fight infections, and maintain overall health. Over time, this leads to systemic failure and eventual death of the host.
The cellular uniformity of BTN cells across infected individuals adds another dimension to their impact. Because the cells are genetically identical, BTN essentially acts as a clonal invader, bypassing the host’s natural defenses and proliferating unchecked. This makes BTN especially devastating for bivalve populations, as they often lack the genetic diversity needed to mount an effective defense.
The Role of Bivalves in Marine Ecosystems
Bivalves play a crucial role in keeping the ecological integrity of aquatic environments intact. As filter feeders, habitat creators, and nutrient cyclers, they provide many services that benefit these environments. But, the spread of BTN is a threat to these critical services, endangering the ecosystems that rely on these bivalves.
Water Filtration and Nutrient Cycling
Bivalves are natural water purifiers. A single mussel can filter up to 25 liters of water per day. This filtration removes particulates and harmful pathogens, among other undesirables in the water 9. This filtration can prevent unwanted algal blooms and in turn helps to support the growth of submerged aquatic vegetation and other species 10. The value of nutrient remediation by bivalves has been estimated at $1.2 billion annually, underscoring how important they are for water quality management 9
BTN induced declines in bivalve populations compromise this essential role they fill. Without adequate filtration, coastal ecosystems become vulnerable to things like hypoxia and biodiversity loss. The cascading effects of these can be huge, impacting fish populations, seagrass beds, and human livelihoods that depend on healthy marine environments.
Habitat Engineers
Bivalves are also architects of their ecosystems. Mussel beds and oyster reefs provide complex, three-dimensional habitats that support a diverse array of marine organisms, from small invertebrates to commercially important fish species 10.These structures stabilize sediments, thus reducing erosion. They can also increase biodiversity, acting as ecological hotspots in marine environments.
The loss of these habitats due to BTN can lead to trophic cascades, where declines in bivalve populations ripple through the food web. Species that rely on bivalve beds for shelter or foraging, such as juvenile fish and crustaceans, may struggle to survive, leading to further imbalances in the ecosystem 10.
Keystone Species in Danger?
Many BTN affected bivalves exhibit traits of keystone species, organisms that play critical roles in maintaining an ecological community to the point that its removal would cause significant changes or even collapse of an ecosystem. Bivalves exert outsized influence on their environments relative to their abundance. Their filtration and habitat creation roles underpin the functioning of entire ecosystems. While direct studies on their keystone status are limited, the ecological consequences of their decline suggest a keystone-ish role 10.
Economic and Cultural Significance
Beyond their ecological contributions, bivalves have significant economic and cultural value. The global aquaculture industry for bivalves is worth nearly $24 billion annually, with additional non-market ecosystem services, such as nutrient remediation and carbon storage, valued at over $6 billion 9. BTN threatens these economic benefits by reducing harvests and increasing management costs.
Bivalves also hold cultural importance, from their role in traditional diets to their symbolic significance in art and heritage. Coastal communities worldwide celebrate bivalves through seafood festivals and artisanal fisheries, which foster local pride and contribute to regional economies. The spread of BTN risks eroding these cultural connections 9.
Ripple Effects
The ecological balance maintained by bivalves is intricate, and BTN disrupts it in ways that are difficult to fully predict. By threatening these species, BTN jeopardizes not only the biodiversity of marine ecosystems but also the services and benefits that humans derive from them. As researchers work to combat BTN, preserving the ecological roles of bivalves must remain a central focus, ensuring these vital creatures continue to support the health of our oceans.
Incremental Progress Over Perfect Solutions
The spread of BTN exemplifies a broader truth about marine diseases: some problems are too large, too complex, and too intertwined with global ecosystems to completely “fix”. BTN’s adaptability, persistence, and ability to spread across species and oceans make it a serious challenge. However, while a perfect solution likely doesn’t exist, there is value in incremental progress to buy time for bivalve populations and the ecosystems they sustain.
What Can Be Done?
1. Monitoring, Not Eradicating
BTN’s stealthy nature and global spread make eradication impossible, but early detection offers a glimmer of hope. Hemolymph testing and environmental DNA (eDNA) surveys can provide critical data about where BTN is most active 11. These tools won’t stop BTN, but they can help identify hotspots where intervention might prevent further spread.
2. Localized Conservation
Marine protected areas and reef restoration projects won’t save bivalves globally, but they can create safe havens in critical ecosystems. Localized efforts ensure that at least some populations stick around, helping to preserve biodiversity and ecosystem function in the targeted regions 9,10.
3. Adaptation, Not Control
Selective breeding programs aimed at enhancing BTN resistance may seem like a technological fix, but they’re better understood as one piece of a much larger puzzle. By nudging evolution in a favorable direction, researchers can buy time for bivalves to adapt naturally 1. However, these efforts face significant ecological and logistical challenges, especially for species in the wild.
4. Living With BTN
BTN might ultimately be something ecosystems must adjust to, just as they have adapted to invasive species and climate-driven shifts. Some bivalve populations may develop resistance, as seen in a few Pacific blue mussel populations that show signs of naturally blocking BTN infection 3. Supporting these natural adaptations through habitat restoration and pollution reduction may be more realistic than large-scale interventions.
Accepting Complexity
BTN’s global and systemic nature means there’s no “silver bullet” solution. And that’s okay. Embracing the complexity of the problem allows conservationists, researchers, and policymakers to set more realistic goals. Protecting biodiversity, supporting sustainable aquaculture, and improving ocean health are worthwhile endeavors even if BTN continues to exist. These actions benefit ecosystems broadly, and in doing so, may also reduce BTN’s impacts.
Citations
1. Hart SFM, Yonemitsu MA, Giersch RM, et al. Centuries of genome instability and evolution in soft-shell clam, Mya arenaria, bivalve transmissible neoplasia. Nat Cancer. 2023;4(11):1561-1574. doi:10.1038/s43018-023-00643-7
2. Metzger MJ, Villalba A, Carballal MJ, et al. Widespread transmission of independent cancer lineages within multiple bivalve species. Nature. 2016;534(7609):705-709. doi:10.1038/nature18599
3. Yonemitsu MA, Giersch RM, Polo-Prieto M, et al. A single clonal lineage of transmissible cancer identified in two marine mussel species in South America and Europe. Ostrander E, Wittkopp PJ, eds. eLife. 2019;8:e47788. doi:10.7554/eLife.47788
4. Skazina M, Ponomartsev N, Maiorova M, et al. Genetic features of bivalve transmissible neoplasia in blue mussels from the Kola Bay (Barents Sea) suggest a recent trans-Arctic migration of the cancer lineages. Mol Ecol. 2023;32(21):5724-5741. doi:10.1111/mec.17157
5. Bivalves Transmissible Neoplasia: Biochemical Aspects of Contagious Cancer in a Clam Macoma Balthica. Cell Physiol Biochem. 2022;56(6):629-643. doi:10.33594/000000587
6. Giersch RM, Hart SFM, Reddy SG, et al. Survival and Detection of Bivalve Transmissible Neoplasia from the Soft-Shell Clam Mya arenaria (MarBTN) in Seawater. Pathogens. 2022;11(3):283. doi:10.3390/pathogens11030283
7. Aubier TG, Galipaud M, Erten EY, Kokko H. Transmissible cancers and the evolution of sex under the Red Queen hypothesis. PLoS Biol. 2020;18(11):e3000916. doi:10.1371/journal.pbio.3000916
8. Skazina M, Odintsova N, Maiorova M, Ivanova A, Väinölä R, Strelkov P. First description of a widespread Mytilus trossulus-derived bivalve transmissible cancer lineage in M. trossulus itself. Sci Rep. 2021;11(1):5809. doi:10.1038/s41598-021-85098-5
9. van der Schatte Olivier A, Jones L, Vay LL, Christie M, Wilson J, Malham SK. A global review of the ecosystem services provided by bivalve aquaculture. Rev Aquac. 2020;12(1):3-25. doi:10.1111/raq.12301
10. Vaughn CC, Hoellein TJ. Bivalve Impacts in Freshwater and Marine Ecosystems. Annu Rev Ecol Evol Syst. 2018;49(1):183-208. doi:10.1146/annurev-ecolsys-110617-062703
11. Weinandt SA, Child ZJ, Lartey D, et al. Identification of an Outbreak of Bivalve Transmissible Neoplasia in Soft-Shell Clams (Mya arenaria) in the Puget Sound Using Hemolymph and eDNA Surveys. Published online December 7, 2024:2024.12.03.626659. doi:10.1101/2024.12.03.626659