The zebrafish model of autism

I have to open this post by assuring readers that this is NOT SATIRE.

Go to google scholar ( https://scholar.google.com.au/ ) and type in 'zebrafish', and 'autism'. About 13,000 results? That's what I got.

A couple of these papers were published in 2014, both in journals with 'impact factors' above 10. One paper has been cited 455 times already; the other 305 times.

Titles:
"Zebrafish as an emerging model for studying complex brain disorders", and
"Zebrafish models for translational neuroscience research: from tank to bedside".

This is a very real, established, and publicly funded research program. It encompasses a "Zebrafish model of autism".

About now, you might be a bit perplexed. Perhaps it's all actually about studying genes and proteins, in which anomalies wreak non-specific havoc on all sorts of basic cellular function, in affected primates as much as in fish? That might make sense. But no.

"For brain disorders such as autism ... the use of zebrafish to model social deficits is based on their rich social behaviors. For example, zebrafish are highly social animals and swim in shoals, the disruption of which by various environmental, pharmacological or genetic factor can be easily assessed." See figure below.

The suggestion isn't just that a molecular abnormality which generally causes problems for zebrafish might also cause problems for humans. The suggestion is that the same molecular abnormality which makes zebrafish behave unsociably might also make some humans autistic.

*****

The zebrafish has become popular in laboratories around the world, because "it ticks just about every box on a wish-list of attributes that scientists seek when trying to model human diseases". [ https://www.theguardian.com/science/2013/sep/15/zebrafish-human-genes-project ]

Documented benefits of the zebrafish, to the labs and scientists using it, comprise a long list:

• The zebrafish is small and robust.
• They are cheaper to maintain than mice.
• Break of daylight triggers mating in zebrafish (many other fish only lay eggs in the dark).
• Zebrafish produce hundreds of offspring at weekly intervals providing scientists with an ample supply of embryos to study.
• They grow at an extremely fast rate, developing as much in a day as a human embryo develops in one month.
• Zebrafish embryos are nearly transparent which allows researchers to easily examine the development of internal structures. Every blood vessel in a living zebrafish embryo can be seen using just a low-power microscope.
• As zebrafish eggs are fertilised and develop outside the mother’s body it is an ideal model organism for studying early development.
• Zebrafish have a similar genetic structure to humans. They share 70 per cent of genes with us.  [ https://www.yourgenome.org/facts/why-use-the-zebrafish-in-research ]

The zebrafish model of autism is poor science, sure. Some zebrafish research might be proper science. Some zebrafish research might, indirectly and over the long term, help contribute to greater understanding of some causes of autism. 

But the zebrafish model of autism, as it's currently conceived, isn't a great model.

Is that all there is to this? Shall we sit back and chortle at the millions of research dollars being hoovered up by the International Zebrafish Neuroscience Research Consortium (I keep telling you, no - not satire). Or could there be bigger fish to fry (my apologies)?

I think there could be. I think something else could be going on here as well.

In the absence of competitors, the zebrafish model of autism has come to occupy a small corner of a very big space - the autism explanatory gap. What causes autism? What are the pathophysiological steps which conclude in an individual's autistic makeup? What is autism anyway?

No one claims to have a good answer to these questions. Baron-Cohen's 1985 'theory of mind' theory is probably still the best-known attempt at an explanation. I don't find it a satisfactory explanation, at all. Its pre-eminence seems to be fading in recent years. Baron-Cohen published his theory 41 years after Kanner's landmark paper. 35 years have now passed since Baron-Cohen's publication.

Back to the zebrafish. There's an old joke which captures the logic of the zebrafish model of autism, better than I could describe (or satirise) it. The nearly transparent zebrafish embryo adds allegorical power:

A policeman sees a drunk man searching for something under a streetlight and asks what the drunk has lost. He says he lost his keys and they both look under the streetlight together. After a few minutes the policeman asks if he is sure he lost them here, and the drunk replies, no, he lost them in the park. The policeman asks why he is searching here, and the drunk replies, "this is where the light is".

Papers mentioned:

Kalueff A et al., "Zebrafish as an emerging model for studying complex brain disorders" (2014) 35 Trends in Pharmacological Sciences 63.  https://www.sciencedirect.com/science/article/abs/pii/S0165614713002290

Stewart AM et al., "Zebrafish models for translational neuroscience research: from tank to bedside" (2014) 37 Trends in Neurosciences 264.  https://www.sciencedirect.com/science/article/pii/S0166223614000277

Baron-Cohen, S et al.,  "Does the autistic child have a theory of mind?" (1985) 21 Cognition 37.  http://pages.uoregon.edu/eherman/teaching/texts/Baron-Cohen%20Leslie%20Frith%20Does%20the%20Autistic%20Child%20Have%20a%20Theory%20of%20Mind.pdf

Kanner, L, "Early infantile autism" (1944) 25 Journal of Pediatrics 211.  https://www.jpeds.com/article/S0022-3476(44)80156-1/abstract