The Zebrafish Model: A Powerful Tool for Answering Complex Questions

We knew the model was brilliant for academic research. Would it be as good for modeling human disease and discovering new drugs in an industrial setting?

Why zebrafish is a useful tool?

When discussing which should be the first article of this news, we came up with several topics. All of them aimed at reflecting the work we develop at ZeClinics: “How to use zebrafish for this…” or “Why zebrafish is a useful tool for that…”. Soon, we realized this collection of articles should start by the primary question (and we don’t mean why we are in the universe): Why do we use zebrafish at ZeClinics?

For us it is obvious how great zebrafish is for drug and target discovery. Nevertheless, it might not be so much for those not familiar with the model. Thus, as it happens with all good stories, we should start at the beginning.

Circa 2013, four academic scientists (Simone Calzolari, Ignasi Sahún, Davide D’Amico, and Javier Terriente) decided to build a biotech company. Some of us already had a vast experience in the use of zebrafish. As academics, we were exploiting zebrafish experimental and biological advantages for understanding the genetic basis underlying brain development. We had started working with this model under the assumption that zebrafish would provide the experimental simplicity of invertebrate models while allowing a higher translatability toward human biology. We might be rarely right, but in that case, we were spot on.

We knew the model was brilliant for academic research. Would it be as good for modeling human disease and discovering new drugs in an industrial setting?

We don’t like spoilers, but the answer is YES. Now, let’s explain why:

• Take a vertebrate in vivo model (remember, it is an animal, not an in vitro model);
• displaying high genetic homology with humans (82% of orthologous genes, when disease-related genes are considered);
• with human-like tissues and organs (ah! the beauty of the zebrafish beating heart);
• optically transparent (study biological processes happening… as they happen!);
• highly amenable to genetics (more after CRISPR/Cas9 was discovered);
• small, living in water, and with hundreds of larvae to test in parallel (easy administration of drugs + statistical power = high-throughput drug screening);
• considered an in vitro model if you work with larval stages (thumbs up for 3Rs!).

The aforementioned experimental and biological advantages make it obvious why the zebrafish model is the perfect tool, for the pharma and chemical industry, for understanding chemical toxicity, drug efficacy research, and human diseases modeling and understanding. But we still had to prove the model provides biological translatability. Which is to say: are we sure results obtained in zebrafish predict genetic and pharmacological outcomes in humans?

To address that important aspect, we have published several validation articles and reviews in peer-review journals, and all our services have been validated with standards. So yes, we are pretty certain the model is predictive. Most importantly, our R&D efforts are always active: to keep validating the model, to create new tools and services, and to discover our own therapeutics, as we are already doing in our first spin-out company ZeCardio Therapeutics.

We believe in the power of zebrafish for understanding disease and discovering new therapeutics but, importantly, we provide data supporting this assumption.

So… why does ZeClinics use zebrafish? That original question started our company and still fuels our news. In the coming months, this news will be a window into ZeClinics’ scientists, news, and activities. We will showcase our research, providing the “what for”, the “why”, the “how”, and the “what’s next” around the zebrafish model.

For those who want to know more about zebrafish, stay tuned, and reach out if curious. We will be happy to discuss the pros, the cons, and all those unrelated questions that make news fascinating.

By Javier Terriente

Javier is a biochemist with a Ph.D. in developmental genetics. He has more than 20 years of research experience in the Academy and the biotech sector. In 2013, he co-founded ZeClinics. Recently, Javier co-founded ZeCardio Therapeutics. From 2013 to 2020 he was Chief Scientific Officer in ZeClinics, and now acts as Chief of Drug Discovery. Per his role in both companies, Javier manages a growing scientific team, has directed several Ph.D. theses and published multiple research articles, including several articles on the use of zebrafish for drug and target discovery. In addition to these roles, he serves as VP at Asebio, the Spanish association of biotech companies.