Health and Healthcare Systems

The intoxicating science of animal venom. What you need to know

A biochemical arms race has shaped deadly venoms into a powerful medical resource. Image: REUTERS/Kham

Mandë Holford
Associate Professor of Chemical Biology, Hunter College, City University of New York (CUNY)
Marymegan Daly
Professor in Evolution, Ecology and Organismal Biology, The Ohio State University
Ashlee Rowe
Assistant Professor, Department of Biology and Graduate Program in Cellular & Behavioral Neurobiology, University of Oklahoma
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The evolution of venom has transformed and empowered diverse organisms. Our challenge now is to mobilize a global effort to leverage the power of venom to advance science, technology, engineering and education, changing human lives.

What we know

Venomous animals are seen as agents of mystery and danger. However, animal venoms are a powerful, biochemical resource that can be leveraged to resolve global challenges. These range from identifying the origins of biodiversity to mapping the human mind and developing novel pain therapeutics.

The power of venom comes from three key features. First, venoms are complex mixtures of secretions, providing a novel source of biochemicals. Second, despite their complexity, the structure and physiological targets of these biochemicals are conserved throughout the animal kingdom. Venom components can be synthesized, modified and used as probes to study the human nervous system. Third, millions of years of biochemical evolution have shaped venom into a wildly successful innovation found in all branches of the animal tree of life.

Venoms are present in all ecosystems: deserts where giant centipedes and scorpions hunt insects; seas where snails harpoon fish; air where bees and wasps avoid predatory birds; and forests where snakes hunt anything that moves. For animals, venom transforms physical warfare into a biochemical arms race in which David can conquer Goliath. For humans, venoms can both kill and cure. It is in this paradox that the power and challenge of venom lie, transforming it from an agent of fear to one of hope, innovation and prosperity.

Venomics research questions

Basic science, technology and medicine will be advanced by using venom as a transdisciplinary approach to address key questions in biodiversity, neurobiology, genetics and evolution. For example, how has venom influenced global patterns of biodiversity? How do venom components activate or deactivate the human pain pathway to either cause or block pain?

Under what conditions does venom evolve, and are there common ecological or situational factors that underlie the evolution of venom? Does the evolution of venom follow models proposed for other arms races, such as microbial, host-parasite, plant-herbivore and plant-pollinator systems? How have venoms and interactions between venomous animals and their opponents driven speciation and diversification?

Have you read?

Can we identify a phenotype to genotype pattern that predicts which venom compounds will modulate specific molecular targets, such as ion channels and receptors in sensory and neuromuscular tissues? Are venom genomes the key to deciphering cellular function? What can we learn from computational toxicology to advance personalized medicine?

These key research questions about venoms focus on existing and devising new models to understand how cell signalling occurs and how proteins interact. Resolving these questions requires an integrated, translation-focused approach with expertise from a globally diverse scientific community to overcome computational, molecular and functional obstacles, realizing the transformative power of venoms.

Scientific discoveries and desired outcomes

The 2018 Nobel Prize in Chemistry was awarded to Frances Arnold for her groundbreaking work on the directed evolution of enzymes. With the innovation of venoms, nature has done directed evolution. There are unlimited scientific discoveries waiting to be explored. The weaponization of biomolecules is one of the oldest and most ubiquitous strategies for animals, but also one of the most labile, evolving multiple times in the approximate 15% of animal biodiversity that produce venom.

Although biochemical, structural and behavioural aspects of venom are characterized for some lineages, there are no lineages where all of these elements have been fully described and none where these have been interrogated in a comprehensive way so that we can understand the common triggers, pathways and consequences of the evolution of venom.

However, based on the few systems that have been studied, we know that venom chemistry holds promise for improving human health, that venom entails unusual systems for gene transcription and modification, and that the structures used in the deployment of venom have unique physical properties. Characterization of the venom system across animal lineages has the potential for enormous advances across the life sciences, chemistry and bioengineering.

For example, venom will provide insight into the rules and patterns of evolution while also unlocking the mechanisms of cellular and subcellular processes such as ion channel function, gene duplication, neofunctionalization and regulation. The description of venom provides opportunities to document and describe novel biomolecules and novel structures for their delivery.

Few systems offer a natural opportunity for such transdisciplinary, comparative and comprehensive research. Moreover, venomous systems will advance STEM education using the intoxicating draw of venom to teach and inspire students with cross-disciplinary stories about biology, chemistry, biodiversity and bioengineering.

Why invest in venomics now?

The study of venoms is a moonshot for transdisciplinary research that can engage, excite and inspire generations of scientists, students and the lay public for years to come. Indeed, venom research has escalated in the last decade, as evidenced by the global increase in venom publications, symposia and biotech start-up companies. What explains this escalation? The scale and complexity of questions posed demand technologies and scientific foundations that have only recently been realized.

The rise of omics technologies has made it easier, cheaper and faster to study a vast number of species, including non-model organisms that are small or rare. The field is poised for breakthroughs as venoms are rapidly emerging as agents of hope, transformation, innovation and prosperity. In short, an investment in venoms is an investment in scientific advancement pertinent to multiple stakeholders, both inside and outside the research community.

Let’s step up to nature’s challenge and ride the venom train of scientific wonder.

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