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Scotland's gene genius: part II

21 February 2019, at 8:00am

In the second part of the feature, Professor Ross Houston, who is currently involved in using gene editing to improve resistance to diseases in salmon, explains the barriers – technical, regulatory and ethical – that need to be overcome before such techniques might be applied commercially to improve aquaculture production in Europe and beyond.

What do you think can be achieved by gene editing and are the barriers to it primarily legislative, or technical?

We’re focusing on using gene editing to improve disease resistance in salmon and we’ve established the facilities and technology to do the practical side of the genome editing from here – both with newly fertilised embryos and with cell cultures. Cell-culture models have their advantages and disadvantages – they’re easier to work with, but they’re not as close to the final outcome of what you want to measure: which is disease resistance in the animals themselves.

Professor Ross Houston at the Roslin Institute, near Edinburgh
Professor Ross Houston at the Roslin Institute, near Edinburgh

To enable our gene-editing research in fish embryos, we have set up a custom hatchery and disease challenge facility on site at Roslin. It’s split into two parts: the first is a hatchery where we will perform the gene-editing work; the second is set up for conducting disease challenges in juveniles. It’s freshwater only but is suitable for similar research on other fish species, as it’s set up to do warm as well as cold water.

In terms of the process, we’ve had success in targeted editing of the salmon genome in cells and in embryos, but we’ve not yet got the technique to the stage where it’s as efficient as we would like – it’s still a work in progress.

What are the main challenges to overcome?

The main issue for embryo editing is survival – not related to the gene editing itself, but rather due to the micro-injecting of embryos which is used as the delivery method. That’s not a unique issue here – it’s observed in multiple labs, to a greater or lesser extent, that are doing this research. So, we’re doing a lot of work that’s trying to optimise that, and this will then help us to address the scientific questions that we’re asking relating to control of disease resistance.

Even achieving a consistent embryo survival of 50 percent would be great – you see that in some cases, but not consistently. While salmon gametes are relatively inexpensive, they’re sometimes limited in terms of seasonal availability – it can be hard to source them when you need them.

We’re starting to do similar experiments in other species too – for example we have a studentship working on gene editing Pacific oyster larvae – targeting resistance to oyster herpes virus. But we’re going through the same process that we did with salmon, which is trying to get the technique working well.

How does the salmon sector view gene editing?

I think there’s a lot of interest from the salmon breeding companies, as there is among many terrestrial livestock breeding companies. It appears that all of them are doing research into genome editing either themselves, or by collaborating with universities and research institutes. We collaborate too, for example with Anna Wargelius’s group at Norway’s Institute of Marine Research, whose primary target has been achieving novel methods to achieve sterile salmon for production.

Do you think legislative issues can be overcome?

Whether, where and when it will be possible to apply results of commercial or animal welfare value is a very uncertain area. Much will depend on geography – Argentina recently approved a gene-edited tilapia, for example, while in the United States and Canada, the genetically modified AquaBounty salmon is already available for human consumption. Europe, on the other hand, took a fairly conservative stance by regulating gene editing in a similar way to genetic modification.

Although I believe there is a movement towards acceptance of the appropriate use of this technology in Europe, both the regulatory side and public opinion have to be aligned to allow for a commercial application of genome editing.

I also think that – in terms of public perception – the type of application the techniques are used for is very important. For example, if the application can improve the health and welfare of farmed animals, or perhaps prevent damage to the environment, then that’s going to be an easier sell to the public, compared to something that’s purely perceived as being a means for a company to increase its production or profit levels.

What would you view as your ultimate research project?

One exciting avenue that we’re exploring the edges of is whether we can transfer the mechanisms by which some of the salmonid species are more resistant to diseases than others, in particular for sea lice.

Given that sea lice are such a huge industry problem, and the plethora of prevention and control mechanisms that are thrown at them, gene editing can be investigated as a route to help prevent infestations. For example, if we knew the genes, or variants of genes, that are involved in the successful immune response in coho salmon, as compared to the largely unsuccessful response in the Atlantic salmon, this would raise the possibility of mimicking the coho response in the Atlantic. This could be done, in theory, by editing the Atlantic salmon DNA for these genes to match the sequence of the coho salmon.

These, and similar initiatives, are long-term projects, but substantial research related to this topic is already underway, and it could be transformational if it worked.

What are your ambitions in the shorter term?

In terms of gene editing we’re focused on researching host response to viral disease in salmon, and in developing novel control methods for those diseases. I think there are advantages of studying viruses as, typically, you can work in early life with the fish and the cell cultures. Sea lice are that bit more challenging, because you need specialised challenge facilities and the fish are substantially older and larger. There’s no easy or well-established cell-culture system to study sea lice response.

But that’s the gene editing side of it, which is only a small part of our research programme. I’m also very enthused by increasing the uptake in selective breeding, and using technology to do that across numerous species. A lot of global aquaculture still uses wild, or nearly wild, stocks. Even if hatcheries exist, they tend not to be performing genetic improvement – they just tend to be managing the stocks – so there’s huge potential to improve production across various species via well-managed selective-breeding programmes.

And I think some of the technologies we’re using already for salmon can be adapted or applied to different sectors to help that happen. I think that could have a transformational impact on aquaculture production and help it to follow those graphs we frequently see that highlight the increase in seafood production needed to meet a rapidly increasing demand.