Model organisms and translational research

Ewan Birney (Genomic's Big Talker of ENCODE notoriety) has a new post called In defence of model organisms.

He brings up two points that are worth discussing.

What is a model organism?

There are two common definitions. Birney leans toward defining a model organism as one that models human biochemistry and physiology. This is a common definition. It emphasizes the meaning of "model" as "model of something."

The other definition is more like the meaning of model as "ideal" or "useful" as in Cromwell's New Model Army. The two definitions are not mutually exclusive but it's important to recognize the biases when you hear scientists talk about model organisms.

One of the first model organisms was the fruit fly, Drosophila melanogaster. It was easy to culture and had relatively short generation times. As more and more scientists began work on Drosophila genetics, it became a very useful tool for probing all kinds of biological questions. Back in the 1930s, nobody really thought of fruit flies as good models for the study of human diseases.

Later on (1940s), the phage group developed bacteria and bacteriophage as model organisms. They were used to study genetics and basic biological processes. They were convenient because so many different groups were working on the same systems and their knowledge could be readily shared. This is why we know so much about Escherichia coli—an otherwise unremarkable species.

Arabidopsis thaliana is another model organism. Many discussions about model organisms don't mention it. Nor do they mention Daphnia or Neurospora. That's usually because they are going with the first definition of model organism and they don't see these examples as being particularly relevant.

Ewan Birney's point is that more and more health research is directly involved in studying humans and human cell lines. According to him, there's still a place for studying some "model" organisms because we need to understand basic biological processes. In other words, some basic research is necessary in order to understand human medicine. That's why he's "defending" model organisms.

Translational research

Strictly speaking, translational research is research that's directed toward some useful goal or product. These days it's almost always used in the context of research that could prove useful in human medicine.

Ewan Birnely supports translation research and he's upset that there seems to be a conflict between basic science and translational research.

Crude arguments that play “translation” and “basic research”, or “human disease” and “fundamental discoveries” off each other are depressing. The idea that humans are the only model organism for the future is simply misguided mischief, and opens up the dangerous possibility that people might actually start to believe it – and it’s just as frustrating to hear some people claim that one can only do translational, healthcare related science in humans, and no profound basic discoveries will emerge from human investigation. Taking an extreme position to make either point is annoying, but it belies an underlying tension that needs to be resolved. I think these arguments are more about conflict between of tribes of scientists who are now interacting more and more. There is also an element of jockeying for position, both as individuals and as tribes. We need to get beyond this.

A ‘balanced portfolio’ sounds great, but there is no straightforward recipe for compiling one. What does the best ‘balanced portfolio’ of research look like? How much “pure” disease focus on humans, and what else to add? A tablespoon of yeast, a teaspoon of serendipity and a dash of electric eel? What part of that portfolio would a particular funding agency, charity, institute or scheme take on? How to assess a slew of wildly different proposals, each with different rationales?

There are no easy answers to these questions, but we do need to realise that the lines between ‘basic’ and ‘translational’ research are now fully blurred – both are essential parts of the same process of understanding life, with massive spill-over effects across many practical aspects of our world, our health above all.

My view is somewhat different. I think there really is a difference between someone who is studying speciation in Drosophila or the mechanism of photosynthesis and someone who is mostly interested in curing cystic fibrosis.

I think there's a huge difference between basic research and translational research. This does not mean that some of the discoveries of basic researchers will never be relevant to health and disease, of course they will, but that doesn't mean that the "lines are fully blurred." There's still a lot of fundamental basic research addressing questions that have nothing to do with health and disease and will never be relevant.

I don't think we should fall into the trap of justifying fundamental curiosity-motivated research soley on the basis of what it might contribute to the "really important" stuff like translational research. We should be supporting basic research because it contributes to knowledge and not necessarily to health and disease.

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